Septic Shock
Conditions
Keywords
Early Septic Shock
Brief summary
This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of \> 70 pg/ml.
Detailed description
This is a double-blind, placebo-controlled, randomized, multicenter proof of concept and dose-finding phase II study using two doses of ADRECIZUMAB in patients with early septic shock and a bio-ADM plasma concentration at admission of \> 70 pg/ml. Early septic shock is defined as a life-threatening organ dysfunction due to dysregulated host response to a proven or suspected infection which leads to a decline of Mean Arterial Pressure (MAP) \< 65 mmHg, which is refractory to fluid resuscitation and requires vasopressors. Early is defined as a maximum of less than 12 hours between onset of the cardiovascular organ-dysfunction and administration of ADRECIZUMAB. Refractoriness to fluid resuscitation is defined as a lack of response to the administration of 30 mL of fluid per kilogram of body weight or is determined according to a clinician's assessment of inadequate hemodynamic results. It is intended to enroll 300 patients from surgical, medical and mixed ICU at multiple centers in Europe. All patients will be treated according to International Guidelines for Management of Severe Sepsis and Septic Shock. Eligible patients (confirmed by central verification) will be randomized (1:1:2) to ADRECIZUMAB treatment arm A (2 mg/kg) or to ADRECIZUMAB treatment arm B (4 mg/kg) or to placebo as control group. Patients assigned to the treatment arm A or B will be administered a single dose of ADRECIZUMAB as intravenous infusion over approximately 1 hour; patients assigned to the control group will be administered placebo as intravenous infusion over approximately 1 hour. As long as the patients are on the ICU, daily measurements of clinical signs and laboratory data will be collected for safety reasons and for determination of Sequential Organ Failure Assessment Score (SOFA score). Additional blood samples for central laboratory analyses will be taken at inclusion on day 1, day 3, day 5, day 7 or day of discharge (whatever comes first) for measurement of biomarkers. The SOFA score and its components will be determined daily for all patients over the entire stay on the ICU (28 days or until discharge whatever comes first). Safety monitoring for each patient will begin at the time of signing the Informed Consent Form and continue for 90 days after end of short-term infusion of study medication. At selected study centers a pharmacokinetic (PK) substudy will be performed to determine the profile of ADRECIZUMAB in 80 randomized patients. An interim analysis for efficacy is planned after 50% of patients have completed the study (n=150).
Interventions
BIOLOGICALAdrecizumab
Single i.v. dose of 2 mg/kg (treatment arm A) or 4 mg/kg (treatment arm B)
BIOLOGICALPlacebo
Single i.v. dose of placebo (control group)
Sponsors
Adrenomed AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
Double Blind, Placebo-Controlled, Randomized, Multicenter Proof of Concept and Dose-Finding Phase II Clinical Trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent by patient or legal representative (according to country - specific regulations) 2. Male and female patient, age ≥ 18 years 3. Body weight 50 kg - 120 kg 4. Bio-ADM concentration \> 70 pg/ml 5. Patient with early septic shock (start of vasopressor therapy \< 12 hours) 6. Women of childbearing potential must have a negative serum or urine pregnancy test before randomization 7. Highly effective method of contraception must be maintained for 6 months after study start by women of childbearing potential and sexually active men. 8. No care limitation
Exclusion criteria
1. Moribund 2. Pre-existing unstable condition (e.g. a recent cerebral hemorrhage or infarct, a recent acute unstable myocardial infarction (all \< 3 months), congestive heart failure - New York Heart Association (NYHA) Class IV 3. Patients that required cardiopulmonary resuscitation in the last 4 weeks prior to evaluation for enrollment 4. Severe Chronic Obstructive Pulmonary Disease (COPD) with chronic oxygen need at home (GOLD IV) 5. Any organ or bone marrow transplant within the past 24 weeks 6. Uncontrolled serious hemorrhage (≥ 2 units of blood / platelets in the previous 24 hrs.). Patients may be considered for enrollment if bleeding has stopped and patient is otherwise qualified 7. Uncontrolled hematological / oncological malignancies 8. Absolute neutropenia \< 500 per µL 9. Severe chronic liver disease (Child-Pugh C) 10. Systemic fungal infection or active tuberculosis 11. Neuromuscular disorders that impact breathing / spontaneous ventilation 12. Burns \> 30% of body surface 13. Plasmapheresis 14. Breastfeeding women 15. Participation in a clinical trial involving another investigational drug within 4 weeks prior to inclusion 16. Unwilling or unable to be fully evaluated for all follow-up visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion) | 90 days | The endpoints for the primary objective are to determine over the 90 days study period: Interruption of infusion due to intolerability of ADRECIZUMAB |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity | 90 days | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with severe severity treatment emergent events. |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity | 90 days | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with moderate severity treatment emergent events. |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity | 90 days | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with mild severity treatment emergent events. |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality) | 90 days | The endpoints for the primary objective is mortality evaluated over the 90 days study period. |
| Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs) | 90 days | The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SSI and pSSI Excluding the Renal Component | day 14 and day 28 | Sepsis Support Index (SSI) and penalized Sepsis Support Index (pSSI) excluding the renal component. pSSI is a version of the SSI where mortality is given extra weight: Patients being alive during the 14 days' follow up will have an SSI ranging up to 14, while patients who died within that period will be assigned a score of 14 plus the number of days not being alive. Thus the SSI and pSSI score may range between zero and 28. A higher score means a worse outcome. The number of participants analyzed differs per row due to missing data. |
| SSI Weighted for Mortality | day 14 | Sepsis Support Index (SSI) Weighted for Mortality. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. |
| Individual Sepsis Support Index Components | day 14 and day 28 | Individual Sepsis Support Index (SSI) components (hemodynamic, respiratory and renal failure) with and without mortality. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. The number of participants analyzed differs per row due to missing data. |
| Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | 28 days | Sequential Organ Failure Assessment (SOFA) Score: SOFA score change at Day 3 - baseline, delta = difference between maximum and minimum score during ICU stay, mean/maximum/total daily score during ICU stay, SOFA-3 (score limited to cardiovascular, respiratory and renal function). Measured at baseline and Day 3. SOFA score: Minimum possible score is 0, maximum is 24. A higher score meas a worse outcome. Measured at baseline, Day 2 to Day 28. SOFA-3 score: Minimum possible score is 0, maximum is 12. A higher score meas a worse outcome. Measured at baseline, Day 2 to Day 28. |
| Change in Renal Function (Creatinine) | day 1, day 3 and day 7 | Change in renal function as change in creatinine (day 3 - day 1, day 7 - day 1) |
| Duration of Stay at ICU/ Hospital | 90 days | Duration of stay at ICU / hospital. The number of participants analyzed differs per row due to missing data. |
| Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | 28 days | Changes of Mean Arterial Pressure (MAP). Change from baseline to day 28/last day in ICU was calculated (value at day 28 or last collected value minus value at baseline). MAP was collected at screening and daily from day 1 to day 28 or discharge as well as on the follow-up visit day 28. Vital signs were assessed as min/max values within 24 hours except at screening and on the follow-up visit day 28. |
| Changes of Functional Parameter Creatinine During Stay at ICU | 28 days | Changes of creatinine. Measurement for baseline and Day 28 given. Creatinine was measured in the daily blood sample during ICU stay until discharge or Day 28 in a local laboratory assessment. |
| Changes of Functional Parameter Blood Lactate During Stay at ICU | 28 days | Changes of blood lactate from baseline to Day 28 or discharge. Blood lactate was measured in the daily blood sample from baseline to ICU discharge or until Day 28. |
| Changes of Functional Parameter Fluid Balance During Stay at ICU | 28 days | Changes of fluid balance - Last Observed Value. Percentage of Participants with low (\</=1000 mL) and high (\>1000 mL) Fluid balance at the last observed value. Daily fluid intake will be calculated as the sum of all intravenous and oral fluids. The daily fluid output will be calculated as the sum of the volume of urine output, ultrafiltration fluid, drain fluid, and estimated gastrointestinal losses (including stools only in the presence of profound diarrhea). Insensitive losses will not be taken into account because they are difficult to assess reliably. Daily fluid balance (according to baseline patient weight) will be calculated by subtracting the total fluid output from the total intake. |
| Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU | 28 days | Changes of Mid-Regional pro-Adrenomedullin (MR-proADM) between baseline and last observed value. MR-proADM was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). |
| Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU | 28 days | Changes of inflammatory marker Procalcitonine (PCT) between baseline and last observed value. PCT was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). |
| Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU | 28 days | Changes of inflammatory marker Interleukin-6 (IL-6) between baseline and last observed value. IL-6 was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). |
| Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU | 28 days | Changes of dipeptidyl peptidase 3 (DPP3) between baseline and last observed value. DPP3 was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). |
| Vasopressor Use (Drug, Highest Dose) | 28 days | Vasopressor use (drug, highest dose). Vasopressor use was recorded from admission to ICU at time point of diagnosis of septic shock and daily thereafter from day 1 through day 28 or discharge from ICU (whatever comes first). |
| Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | day 28 and day 90 | Patient reported outcomes: Quality of Life Form by EuroQoL Group, version Euro-QoL-5 (day 28 and day 90). Change 1 = Visual analog scale (VAS) at discharge - VAS at day 90. Change 2 = VAS at day 28 - VAS at day 90. Minimum value on the scale is 0, maximum value on the scale is 100. A lower score indicates a worse outcome. As the change between two scores is calculated, a negative number indicates a worsening. |
| Vital Signs | 7 days | Vital signs: heart rate (beat per minute) Change from baseline to Day 7. |
| Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up | day 28 | Penalized Sepsis Support Index (pSSI) at 28 day follow-up, is a version of the SSI where mortality is given extra weight: Patients being alive duringthe 14 days' follow up will have an SSI ranging up to 14 (as defined above), while patients who died within that period will be assigned a score of 14 plus the number of days not being alive. Thus the weighted SSI score may range between zero and 28. A higher score means a worse outcome. |
| Vasopressor Use (Drug, Duration) | 28 days | Vasopressor use (drug, duration). Vasopressor use was recorded from admission to ICU at time point of diagnosis of septic shock and daily thereafter from day 1 through day 28 or discharge from ICU (whatever comes first). |
| Change in Renal Function (penKid) | day 1, day 3 and day 7 | Change in renal function as change in penKid (day 3 - day 1, day 7 - day 1). penKid was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first). |
| Vital Signs - Blood Pressure | 7 days | Vital signs: blood pressure - mean arterial pressure (MAP) mmHg Change from baseline to Day 7. |
| Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU | 28 days | Changes of Partial Pressure of Oxygen in Arterial Blood (PaO2) / Fraction of inspired oxygen (FiO2) from baseline to the last observed value are measured. PaO2 and FiO2 was collected if an arterial line was in place. The arterial blood was assessed for PaO2 and FiO2. Both were measured in mmHg. |
| Efficacy to be Determined by Sepsis Support Index (SSI) | 14 days | The primary efficacy endpoint of this study is the Sepsis Support Index (SSI) defined as: days with organ support or dead within 14 day follow up More precisely: In the time frame of 14 day follow-up, each day on support with vasopressor, and/or mechanical ventilation, and/or renal dysfunction (defined as renal SOFA = 4), or not alive, is counted as 1. The sum over the follow up period is defined as SSI. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. |
| Sepsis Support Index (SSI) | 28 days | Sepsis Support Index (SSI) at 28 day follow-up Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. |
| Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up | day 14 | Penalized Sepsis Support Index (pSSI) at day 14, defined similar to the SSI with the exception that patients that die get penalized by assigning the maximum value, i.e. the pSSI is set to 14 or 28, respectively. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. |
| Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | day 14 and day 28 | Persistent organ dysfunction or death at 14 and 28 day follow-up. Count of participants with either persistent organ dysfunction or death at Day 14 and Day 28. Persistent Organ Dysfunction is defined as the persistence of organ dysfunction requiring supportive technologies during the convalescent phase of critical illness and it is present when a patient has an ongoing requirement for vasopressors, dialysis, or mechanical ventilation at the outcome assessments time points, as defined by Heyland et al.; Persistent organ dysfunction plus death: a novel,composite outcome measure for critical care trials. Critical Care 2011, 15. |
| Mortality Rate | day 28 | Day 28 mortality rate |
Other
| Measure | Time frame | Description |
|---|---|---|
| In Sub-study Key Pharmacokinetic Parameters Peak Plasma Concentrations (Cmax) Are to be Determined in 80 Patients | 28 days | peak plasma concentrations (Cmax). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. |
| In Sub-study Key Pharmacokinetic Parameter Elimination Half-life is to be Determined in 80 Patients | 28 days | elimination half-life (t½). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. |
| In Sub-study Key Pharmacokinetic Parameter Systemic Clearance is to be Determined in 80 Patients | 28 days | systemic clearance (CL). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. |
| In Sub-study Key Pharmacokinetic Parameter Volume of Distribution is to be Determined in 80 Patients | 28 days | volume of distribution (V). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. |
| In Sub-study Key Pharmacokinetic Parameter AUC is to be Determined in 80 Patients | 28 days | systemic exposure : Area under the plasma concentration versus time curve (AUC). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration. |
| In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 28 days | Time to Cmax (tmax) in hours (h) |
Countries
Belgium, France, Germany, Netherlands
Participant flow
Recruitment details
First patient enrolled: 08-Dec-2017 Last patient completed: 20-Dec-2019 Total study duration: 25 months
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm A Intravenous infusion over approximately 1 hour of single i.v. dose of 2 mg/kg Adrecizumab
Adrecizumab: Single i.v. dose of 2 mg/kg | 72 |
| Treatment Arm B Intravenous infusion over approximately 1 hour of single i.v. dose of 4 mg/kg Adrecizumab
Adrecizumab: Single i.v. dose of 4 mg/kg | 77 |
| Control Group Intravenous infusion over approximately 1 hour of single i.v. dose of Placebo of Adrecizumab
Placebo: Single i.v. dose of placebo | 152 |
| Total | 301 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 26 | 24 | 53 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 |
| Overall Study | Pt seen by doctor in digestive surgery | 0 | 1 | 0 |
| Overall Study | Refusal to recall it up to day 90 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | Treatment Arm A | Treatment Arm B | Control Group | Total |
|---|---|---|---|---|
| Age, Continuous | 66.2 years | 68.8 years | 69.3 years | 68.4 years |
| Apache II Score | 31.4 units on a scale | 31.8 units on a scale | 31.5 units on a scale | 31.6 units on a scale |
| Bio-ADM | 284.30 pg/mL (local) | 305.15 pg/mL (local) | 755.92 pg/mL (local) | 527.80 pg/mL (local) |
| Blood lactate | 4.11 mmol/L | 4.19 mmol/L | 4.23 mmol/L | 4.19 mmol/L |
| Body Mass Index (BMI) | 26.41 kg/m^2 | 26.72 kg/m^2 | 27.78 kg/m^2 | 27.18 kg/m^2 |
| Body temperature | 37.06 degrees C | 36.97 degrees C | 37.08 degrees C | 37.05 degrees C |
| Creatinine | 189.649 μmol/L | 199.891 μmol/L | 192.801 μmol/L | 193.854 μmol/L |
| Heart rate | 104.38 bpm | 97.40 bpm | 96.37 bpm | 98.55 bpm |
| Location before ICU admission Home | 7 participants | 9 participants | 8 participants | 24 participants |
| Location before ICU admission Hospital | 65 participants | 68 participants | 144 participants | 277 participants |
| Mean arterial pressure | 73.18 mmHg | 71.35 mmHg | 72.49 mmHg | 72.36 mmHg |
| Origin of sepsis Bile duct infection | 4 participants | 5 participants | 6 participants | 15 participants |
| Origin of sepsis Blood stream | 4 participants | 5 participants | 6 participants | 15 participants |
| Origin of sepsis Catheter | 0 participants | 0 participants | 4 participants | 4 participants |
| Origin of sepsis Central nervous system | 1 participants | 1 participants | 1 participants | 3 participants |
| Origin of sepsis Lung | 14 participants | 17 participants | 32 participants | 63 participants |
| Origin of sepsis Other | 17 participants | 14 participants | 27 participants | 58 participants |
| Origin of sepsis Peritonitis | 12 participants | 17 participants | 36 participants | 65 participants |
| Origin of sepsis Skin and soft tissue | 2 participants | 8 participants | 14 participants | 24 participants |
| Origin of sepsis Urinary tract | 18 participants | 10 participants | 26 participants | 54 participants |
| Race/Ethnicity, Customized Asian | 1 participants | 1 participants | 3 participants | 5 participants |
| Race/Ethnicity, Customized Black | 1 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Caucasian | 56 participants | 58 participants | 107 participants | 221 participants |
| Race/Ethnicity, Customized Not reported | 13 participants | 17 participants | 41 participants | 71 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants | 2 participants |
| Region of Enrollment Belgium | 23 participants | 24 participants | 43 participants | 90 participants |
| Region of Enrollment France | 30 participants | 30 participants | 64 participants | 124 participants |
| Region of Enrollment Germany | 11 participants | 13 participants | 26 participants | 50 participants |
| Region of Enrollment Netherlands | 8 participants | 10 participants | 19 participants | 37 participants |
| Respiratory rate | 23.63 breaths/min | 21.90 breaths/min | 21.96 breaths/min | 22.34 breaths/min |
| Sequential Organ Failure Assessment (SOFA) Score | 10.1 units on a scale | 10.0 units on a scale | 9.6 units on a scale | 9.9 units on a scale |
| Sex: Female, Male Female | 27 Participants | 24 Participants | 66 Participants | 117 Participants |
| Sex: Female, Male Male | 45 Participants | 53 Participants | 86 Participants | 184 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 26 / 72 | 24 / 77 | 54 / 152 |
| other Total, other adverse events | 44 / 72 | 68 / 77 | 84 / 152 |
| serious Total, serious adverse events | 46 / 72 | 42 / 77 | 96 / 152 |
Outcome results
Primary
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs)
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group.
Time frame: 90 days
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm A | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs) | 68 Participants |
| Treatment Arm B | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs) | 74 Participants |
| Adrecizumab Overall | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs) | 142 Participants |
| Control Group | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Frequency of TEAEs) | 142 Participants |
Primary
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion)
The endpoints for the primary objective are to determine over the 90 days study period: Interruption of infusion due to intolerability of ADRECIZUMAB
Time frame: 90 days
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm A | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion) | 0 Interruptions |
| Treatment Arm B | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion) | 1 Interruptions |
| Adrecizumab Overall | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion) | 1 Interruptions |
| Control Group | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Interruption of Infusion) | 0 Interruptions |
Primary
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality)
The endpoints for the primary objective is mortality evaluated over the 90 days study period.
Time frame: 90 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality) | 63.1453 days | Standard Error 4.094 |
| Treatment Arm B | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality) | 63.1578 days | Standard Error 3.5967 |
| Adrecizumab Overall | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality) | 64.5744 days | Standard Error 2.7582 |
| Control Group | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Mortality) | 63.9809 days | Standard Error 2.9466 |
Primary
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with mild severity treatment emergent events.
Time frame: 90 days
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm A | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity | 39 Participants |
| Treatment Arm B | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity | 46 Participants |
| Adrecizumab Overall | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity | 85 Participants |
| Control Group | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Mild Severity | 82 Participants |
Primary
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with moderate severity treatment emergent events.
Time frame: 90 days
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm A | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity | 54 Participants |
| Treatment Arm B | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity | 60 Participants |
| Adrecizumab Overall | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity | 114 Participants |
| Control Group | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Moderate Severity | 109 Participants |
Primary
Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity
The endpoints for the primary objective are to determine over the 90 days study period. Number of participants with treatment-emergent adverse events per treatment group with severe severity treatment emergent events.
Time frame: 90 days
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm A | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity | 51 Participants |
| Treatment Arm B | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity | 54 Participants |
| Adrecizumab Overall | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity | 105 Participants |
| Control Group | Endpoints for Primary Objective (Safety and Tolerability of Adrecizumab: Severity and Frequency of TEAEs) - Severe Severity | 108 Participants |
Secondary
Change in Renal Function (Creatinine)
Change in renal function as change in creatinine (day 3 - day 1, day 7 - day 1)
Time frame: day 1, day 3 and day 7
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Change in Renal Function (Creatinine) | creatinine change baseline to day 3 | -27.9 μmol/L | Standard Deviation 85.65 |
| Treatment Arm A | Change in Renal Function (Creatinine) | creatinine change baseline to day 7 | -46.6 μmol/L | Standard Deviation 140.38 |
| Treatment Arm B | Change in Renal Function (Creatinine) | creatinine change baseline to day 7 | -44.9 μmol/L | Standard Deviation 98.44 |
| Treatment Arm B | Change in Renal Function (Creatinine) | creatinine change baseline to day 3 | -11.7 μmol/L | Standard Deviation 77.99 |
| Adrecizumab Overall | Change in Renal Function (Creatinine) | creatinine change baseline to day 3 | -27.9 μmol/L | Standard Deviation 85.65 |
| Adrecizumab Overall | Change in Renal Function (Creatinine) | creatinine change baseline to day 7 | -45.7 μmol/L | Standard Deviation 120.1 |
| Control Group | Change in Renal Function (Creatinine) | creatinine change baseline to day 3 | -25.6 μmol/L | Standard Deviation 109.12 |
| Control Group | Change in Renal Function (Creatinine) | creatinine change baseline to day 7 | -50.5 μmol/L | Standard Deviation 125.35 |
Secondary
Change in Renal Function (penKid)
Change in renal function as change in penKid (day 3 - day 1, day 7 - day 1). penKid was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first).
Time frame: day 1, day 3 and day 7
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Change in Renal Function (penKid) | PenKid change baseline to day 3 | -28.3 pmol/L | Standard Deviation 57.25 |
| Treatment Arm A | Change in Renal Function (penKid) | PenKid change baseline to day 7 | -19.5 pmol/L | Standard Deviation 83.88 |
| Treatment Arm B | Change in Renal Function (penKid) | PenKid change baseline to day 7 | -19.7 pmol/L | Standard Deviation 70.8 |
| Treatment Arm B | Change in Renal Function (penKid) | PenKid change baseline to day 3 | -21.4 pmol/L | Standard Deviation 59.07 |
| Adrecizumab Overall | Change in Renal Function (penKid) | PenKid change baseline to day 7 | -19.6 pmol/L | Standard Deviation 77.11 |
| Adrecizumab Overall | Change in Renal Function (penKid) | PenKid change baseline to day 3 | -24.8 pmol/L | Standard Deviation 58.1 |
| Control Group | Change in Renal Function (penKid) | PenKid change baseline to day 3 | -34.8 pmol/L | Standard Deviation 63.91 |
| Control Group | Change in Renal Function (penKid) | PenKid change baseline to day 7 | -29.8 pmol/L | Standard Deviation 83.27 |
Secondary
Changes of Functional Parameter Blood Lactate During Stay at ICU
Changes of blood lactate from baseline to Day 28 or discharge. Blood lactate was measured in the daily blood sample from baseline to ICU discharge or until Day 28.
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Blood Lactate During Stay at ICU | -1.94 mmol/L | Standard Deviation 3.133 |
| Treatment Arm B | Changes of Functional Parameter Blood Lactate During Stay at ICU | -1.54 mmol/L | Standard Deviation 5.247 |
| Adrecizumab Overall | Changes of Functional Parameter Blood Lactate During Stay at ICU | -1.74 mmol/L | Standard Deviation 4.34 |
| Control Group | Changes of Functional Parameter Blood Lactate During Stay at ICU | -1.49 mmol/L | Standard Deviation 7.158 |
Secondary
Changes of Functional Parameter Creatinine During Stay at ICU
Changes of creatinine. Measurement for baseline and Day 28 given. Creatinine was measured in the daily blood sample during ICU stay until discharge or Day 28 in a local laboratory assessment.
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Creatinine During Stay at ICU | Baseline | 189.649 μmol/L | Standard Deviation 116.1689 |
| Treatment Arm A | Changes of Functional Parameter Creatinine During Stay at ICU | Day 28 | 84.217 μmol/L | Standard Deviation 88.1051 |
| Treatment Arm B | Changes of Functional Parameter Creatinine During Stay at ICU | Day 28 | 79.488 μmol/L | Standard Deviation 65.9763 |
| Treatment Arm B | Changes of Functional Parameter Creatinine During Stay at ICU | Baseline | 199.891 μmol/L | Standard Deviation 130.9752 |
| Adrecizumab Overall | Changes of Functional Parameter Creatinine During Stay at ICU | Baseline | 194.944 μmol/L | Standard Deviation 123.7293 |
| Adrecizumab Overall | Changes of Functional Parameter Creatinine During Stay at ICU | Day 28 | 81.380 μmol/L | Standard Deviation 73.3867 |
| Control Group | Changes of Functional Parameter Creatinine During Stay at ICU | Baseline | 192.801 μmol/L | Standard Deviation 131.6193 |
| Control Group | Changes of Functional Parameter Creatinine During Stay at ICU | Day 28 | 153.072 μmol/L | Standard Deviation 120.3464 |
Secondary
Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU
Changes of dipeptidyl peptidase 3 (DPP3) between baseline and last observed value. DPP3 was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first).
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU | -11.56 ng/mL | Standard Deviation 53.03 |
| Treatment Arm B | Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU | -12.47 ng/mL | Standard Deviation 42.27 |
| Adrecizumab Overall | Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU | -12.03 ng/mL | Standard Deviation 47.596 |
| Control Group | Changes of Functional Parameter Dipeptidyl Peptidase 3 (DPP3) During Stay at ICU | -9.38 ng/mL | Standard Deviation 122.031 |
Secondary
Changes of Functional Parameter Fluid Balance During Stay at ICU
Changes of fluid balance - Last Observed Value. Percentage of Participants with low (\</=1000 mL) and high (\>1000 mL) Fluid balance at the last observed value. Daily fluid intake will be calculated as the sum of all intravenous and oral fluids. The daily fluid output will be calculated as the sum of the volume of urine output, ultrafiltration fluid, drain fluid, and estimated gastrointestinal losses (including stools only in the presence of profound diarrhea). Insensitive losses will not be taken into account because they are difficult to assess reliably. Daily fluid balance (according to baseline patient weight) will be calculated by subtracting the total fluid output from the total intake.
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Fluid Balance During Stay at ICU | Low | 80.6 percentage of participants |
| Treatment Arm A | Changes of Functional Parameter Fluid Balance During Stay at ICU | High | 19.4 percentage of participants |
| Treatment Arm B | Changes of Functional Parameter Fluid Balance During Stay at ICU | High | 15.6 percentage of participants |
| Treatment Arm B | Changes of Functional Parameter Fluid Balance During Stay at ICU | Low | 84.4 percentage of participants |
| Adrecizumab Overall | Changes of Functional Parameter Fluid Balance During Stay at ICU | Low | 82.6 percentage of participants |
| Adrecizumab Overall | Changes of Functional Parameter Fluid Balance During Stay at ICU | High | 17.4 percentage of participants |
| Control Group | Changes of Functional Parameter Fluid Balance During Stay at ICU | Low | 80.9 percentage of participants |
| Control Group | Changes of Functional Parameter Fluid Balance During Stay at ICU | High | 18.4 percentage of participants |
Secondary
Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU
Changes of inflammatory marker Interleukin-6 (IL-6) between baseline and last observed value. IL-6 was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first).
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU | -27648.3 pg/mL | Standard Deviation 72859.19 |
| Treatment Arm B | Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU | -37780.4 pg/mL | Standard Deviation 119945.41 |
| Adrecizumab Overall | Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU | -32872.7 pg/mL | Standard Deviation 99694.28 |
| Control Group | Changes of Functional Parameter Inflammatory Marker Interleukin-6 (IL-6) During Stay at ICU | -26236.2 pg/mL | Standard Deviation 70315.5 |
Secondary
Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU
Changes of inflammatory marker Procalcitonine (PCT) between baseline and last observed value. PCT was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first).
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU | -41.402 ng/mL | Standard Deviation 125.0852 |
| Treatment Arm B | Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU | -52.661 ng/mL | Standard Deviation 78.1064 |
| Adrecizumab Overall | Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU | -47.208 ng/mL | Standard Deviation 103.2929 |
| Control Group | Changes of Functional Parameter Inflammatory Marker Procalcitonine (PCT) During Stay at ICU | -37.219 ng/mL | Standard Deviation 78.3425 |
Secondary
Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU
Changes of Mean Arterial Pressure (MAP). Change from baseline to day 28/last day in ICU was calculated (value at day 28 or last collected value minus value at baseline). MAP was collected at screening and daily from day 1 to day 28 or discharge as well as on the follow-up visit day 28. Vital signs were assessed as min/max values within 24 hours except at screening and on the follow-up visit day 28.
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Change from Baseline (minimum) | -7.2 mmHg | Standard Deviation 21.36 |
| Treatment Arm A | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Change from Baseline (maximum) | 18.9 mmHg | Standard Deviation 23.64 |
| Treatment Arm B | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Change from Baseline (maximum) | 17.9 mmHg | Standard Deviation 19.73 |
| Treatment Arm B | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Change from Baseline (minimum) | -6.2 mmHg | Standard Deviation 18.44 |
| Adrecizumab Overall | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Change from Baseline (minimum) | -6.7 mmHg | Standard Deviation 19.84 |
| Adrecizumab Overall | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Change from Baseline (maximum) | 18.4 mmHg | Standard Deviation 21.64 |
| Control Group | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Change from Baseline (minimum) | -6.4 mmHg | Standard Deviation 23.52 |
| Control Group | Changes of Functional Parameter Mean Arterial Pressure During Stay at ICU | Change from Baseline (maximum) | 20.2 mmHg | Standard Deviation 21.26 |
Secondary
Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU
Changes of Mid-Regional pro-Adrenomedullin (MR-proADM) between baseline and last observed value. MR-proADM was measured in the blood samples taken during the ICU stay prior to start of IMP infusion (day 1) and within the time frame of 24 hours (+/- 10 hours) after end of IMP infusion (day 2), at 48 hours, 96 hours and 144 hours after end of infusion (+/- 10 hours) or between scheduled assessments, if discharged earlier from ICU (whatever comes first).
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU | -5.029 mmol/L | Standard Deviation 5.2829 |
| Treatment Arm B | Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU | -4.608 mmol/L | Standard Deviation 4.9512 |
| Adrecizumab Overall | Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU | -4.815 mmol/L | Standard Deviation 5.1006 |
| Control Group | Changes of Functional Parameter Mid-Regional Pro-Adrenomedullin (MR-proADM) During Stay at ICU | -4.030 mmol/L | Standard Deviation 5.2887 |
Secondary
Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU
Changes of Partial Pressure of Oxygen in Arterial Blood (PaO2) / Fraction of inspired oxygen (FiO2) from baseline to the last observed value are measured. PaO2 and FiO2 was collected if an arterial line was in place. The arterial blood was assessed for PaO2 and FiO2. Both were measured in mmHg.
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU | 39.83 ratio | Standard Deviation 155.237 |
| Treatment Arm B | Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU | 63.80 ratio | Standard Deviation 156.771 |
| Adrecizumab Overall | Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU | 52.08 ratio | Standard Deviation 155.896 |
| Control Group | Changes of Functional Parameter Partial Pressure of Oxygen in Arterial Blood(PaO2) / Fraction of Inspired Oxygen (FiO2) During Stay at ICU | 15.91 ratio | Standard Deviation 164.238 |
Secondary
Duration of Stay at ICU/ Hospital
Duration of stay at ICU / hospital. The number of participants analyzed differs per row due to missing data.
Time frame: 90 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Duration of Stay at ICU/ Hospital | Duration of hospital stay | 12.3 days | Standard Deviation 11.87 |
| Treatment Arm A | Duration of Stay at ICU/ Hospital | Duration of ICU stay | 9.6 days | Standard Deviation 6.27 |
| Treatment Arm B | Duration of Stay at ICU/ Hospital | Duration of ICU stay | 11.0 days | Standard Deviation 7.26 |
| Treatment Arm B | Duration of Stay at ICU/ Hospital | Duration of hospital stay | 13.4 days | Standard Deviation 7.71 |
| Adrecizumab Overall | Duration of Stay at ICU/ Hospital | Duration of hospital stay | 12.8 days | Standard Deviation 10.2 |
| Adrecizumab Overall | Duration of Stay at ICU/ Hospital | Duration of ICU stay | 10.3 days | Standard Deviation 6.77 |
| Control Group | Duration of Stay at ICU/ Hospital | Duration of hospital stay | 11.2 days | Standard Deviation 7.72 |
| Control Group | Duration of Stay at ICU/ Hospital | Duration of ICU stay | 9.3 days | Standard Deviation 7.23 |
Secondary
Efficacy to be Determined by Sepsis Support Index (SSI)
The primary efficacy endpoint of this study is the Sepsis Support Index (SSI) defined as: days with organ support or dead within 14 day follow up More precisely: In the time frame of 14 day follow-up, each day on support with vasopressor, and/or mechanical ventilation, and/or renal dysfunction (defined as renal SOFA = 4), or not alive, is counted as 1. The sum over the follow up period is defined as SSI. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome.
Time frame: 14 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Efficacy to be Determined by Sepsis Support Index (SSI) | 8.4 score on a scale | Standard Deviation 5.16 |
| Treatment Arm B | Efficacy to be Determined by Sepsis Support Index (SSI) | 9.1 score on a scale | Standard Deviation 5.2 |
| Adrecizumab Overall | Efficacy to be Determined by Sepsis Support Index (SSI) | 8.8 score on a scale | Standard Deviation 5.18 |
| Control Group | Efficacy to be Determined by Sepsis Support Index (SSI) | 8.1 score on a scale | Standard Deviation 5.41 |
Secondary
Individual Sepsis Support Index Components
Individual Sepsis Support Index (SSI) components (hemodynamic, respiratory and renal failure) with and without mortality. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome. The number of participants analyzed differs per row due to missing data.
Time frame: day 14 and day 28
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Individual Sepsis Support Index Components | SSI renal failure component day 14 | 1.3 score on a scale | Standard Deviation 3.55 |
| Treatment Arm A | Individual Sepsis Support Index Components | SSI cardiac component day 14 | 4.0 score on a scale | Standard Deviation 2.95 |
| Treatment Arm A | Individual Sepsis Support Index Components | SSI respiratory component day 14 | 5.4 score on a scale | Standard Deviation 5.41 |
| Treatment Arm A | Individual Sepsis Support Index Components | SSI death component day 28 | 4.9 score on a scale | Standard Deviation 9.23 |
| Treatment Arm A | Individual Sepsis Support Index Components | SSI cardiac component day 28 | 4.8 score on a scale | Standard Deviation 5.03 |
| Treatment Arm A | Individual Sepsis Support Index Components | SSI renal failure component day 28 | 1.9 score on a scale | Standard Deviation 5.3 |
| Treatment Arm A | Individual Sepsis Support Index Components | SSI respiratory component day 28 | 6.9 score on a scale | Standard Deviation 9.14 |
| Treatment Arm A | Individual Sepsis Support Index Components | SSI death component day 14 | 1.7 score on a scale | Standard Deviation 3.86 |
| Treatment Arm B | Individual Sepsis Support Index Components | SSI respiratory component day 28 | 9.6 score on a scale | Standard Deviation 9.85 |
| Treatment Arm B | Individual Sepsis Support Index Components | SSI renal failure component day 14 | 1.5 score on a scale | Standard Deviation 3.27 |
| Treatment Arm B | Individual Sepsis Support Index Components | SSI cardiac component day 28 | 5.8 score on a scale | Standard Deviation 5.61 |
| Treatment Arm B | Individual Sepsis Support Index Components | SSI renal failure component day 28 | 1.9 score on a scale | Standard Deviation 4.63 |
| Treatment Arm B | Individual Sepsis Support Index Components | SSI death component day 14 | 1.6 score on a scale | Standard Deviation 4.02 |
| Treatment Arm B | Individual Sepsis Support Index Components | SSI respiratory component day 14 | 7.3 score on a scale | Standard Deviation 5.98 |
| Treatment Arm B | Individual Sepsis Support Index Components | SSI cardiac component day 14 | 5.4 score on a scale | Standard Deviation 4.01 |
| Treatment Arm B | Individual Sepsis Support Index Components | SSI death component day 28 | 4.5 score on a scale | Standard Deviation 9.07 |
| Adrecizumab Overall | Individual Sepsis Support Index Components | SSI respiratory component day 14 | 6.4 score on a scale | Standard Deviation 5.78 |
| Adrecizumab Overall | Individual Sepsis Support Index Components | SSI death component day 14 | 1.6 score on a scale | Standard Deviation 3.93 |
| Adrecizumab Overall | Individual Sepsis Support Index Components | SSI death component day 28 | 4.7 score on a scale | Standard Deviation 9.12 |
| Adrecizumab Overall | Individual Sepsis Support Index Components | SSI cardiac component day 28 | 5.3 score on a scale | Standard Deviation 5.35 |
| Adrecizumab Overall | Individual Sepsis Support Index Components | SSI renal failure component day 28 | 1.9 score on a scale | Standard Deviation 4.93 |
| Adrecizumab Overall | Individual Sepsis Support Index Components | SSI respiratory component day 28 | 8.3 score on a scale | Standard Deviation 9.57 |
| Adrecizumab Overall | Individual Sepsis Support Index Components | SSI cardiac component day 14 | 4.7 score on a scale | Standard Deviation 3.6 |
| Adrecizumab Overall | Individual Sepsis Support Index Components | SSI renal failure component day 14 | 1.4 score on a scale | Standard Deviation 3.39 |
| Control Group | Individual Sepsis Support Index Components | SSI death component day 28 | 5.5 score on a scale | Standard Deviation 9.81 |
| Control Group | Individual Sepsis Support Index Components | SSI cardiac component day 14 | 4.6 score on a scale | Standard Deviation 3.84 |
| Control Group | Individual Sepsis Support Index Components | SSI cardiac component day 28 | 4.7 score on a scale | Standard Deviation 4.55 |
| Control Group | Individual Sepsis Support Index Components | SSI respiratory component day 14 | 5.1 score on a scale | Standard Deviation 5.57 |
| Control Group | Individual Sepsis Support Index Components | SSI respiratory component day 28 | 5.8 score on a scale | Standard Deviation 8.08 |
| Control Group | Individual Sepsis Support Index Components | SSI renal failure component day 14 | 1.4 score on a scale | Standard Deviation 3.37 |
| Control Group | Individual Sepsis Support Index Components | SSI renal failure component day 28 | 1.4 score on a scale | Standard Deviation 3.79 |
| Control Group | Individual Sepsis Support Index Components | SSI death component day 14 | 2.0 score on a scale | Standard Deviation 4.34 |
Secondary
Mortality Rate
Day 28 mortality rate
Time frame: day 28
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Mortality Rate | 20.3484 days | Standard Error 0.8694 |
| Treatment Arm B | Mortality Rate | 17.5630 days | Standard Error 0.6592 |
| Adrecizumab Overall | Mortality Rate | 20.5162 days | Standard Error 0.5903 |
| Control Group | Mortality Rate | 22.8783 days | Standard Error 0.7627 |
Secondary
Patient Reported Outcomes : Quality of Life by Euro-QoL-5
Patient reported outcomes: Quality of Life Form by EuroQoL Group, version Euro-QoL-5 (day 28 and day 90). Change 1 = Visual analog scale (VAS) at discharge - VAS at day 90. Change 2 = VAS at day 28 - VAS at day 90. Minimum value on the scale is 0, maximum value on the scale is 100. A lower score indicates a worse outcome. As the change between two scores is calculated, a negative number indicates a worsening.
Time frame: day 28 and day 90
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Change 1 | -13.4 score on a scale | Standard Deviation 22.11 |
| Treatment Arm A | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Change 2 | -11.8 score on a scale | Standard Deviation 16.21 |
| Treatment Arm B | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Change 2 | -10.2 score on a scale | Standard Deviation 19.4 |
| Treatment Arm B | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Change 1 | -19.3 score on a scale | Standard Deviation 22.76 |
| Adrecizumab Overall | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Change 1 | -16.5 score on a scale | Standard Deviation 22.45 |
| Adrecizumab Overall | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Change 2 | -11.0 score on a scale | Standard Deviation 17.83 |
| Control Group | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Change 1 | -7.6 score on a scale | Standard Deviation 27.49 |
| Control Group | Patient Reported Outcomes : Quality of Life by Euro-QoL-5 | Change 2 | -5.9 score on a scale | Standard Deviation 21.5 |
Secondary
Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up
Penalized Sepsis Support Index (pSSI) at day 14, defined similar to the SSI with the exception that patients that die get penalized by assigning the maximum value, i.e. the pSSI is set to 14 or 28, respectively. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome.
Time frame: day 14
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up | 8.5 score on a scale | Standard Deviation 5.26 |
| Treatment Arm B | Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up | 9.1 score on a scale | Standard Deviation 5.2 |
| Adrecizumab Overall | Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up | 8.8 score on a scale | Standard Deviation 5.22 |
| Control Group | Penalized Sepsis Support Index (pSSI) at 14 Day Follow-up | 8.1 score on a scale | Standard Deviation 5.42 |
Secondary
Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up
Penalized Sepsis Support Index (pSSI) at 28 day follow-up, is a version of the SSI where mortality is given extra weight: Patients being alive duringthe 14 days' follow up will have an SSI ranging up to 14 (as defined above), while patients who died within that period will be assigned a score of 14 plus the number of days not being alive. Thus the weighted SSI score may range between zero and 28. A higher score means a worse outcome.
Time frame: day 28
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up | 13.8 score on a scale | Standard Deviation 11.34 |
| Treatment Arm B | Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up | 14.8 score on a scale | Standard Deviation 10.87 |
| Adrecizumab Overall | Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up | 14.3 score on a scale | Standard Deviation 11.07 |
| Control Group | Penalized Sepsis Support Index (pSSI) at 28 Day Follow-up | 13.2 score on a scale | Standard Deviation 11.36 |
Secondary
Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up
Persistent organ dysfunction or death at 14 and 28 day follow-up. Count of participants with either persistent organ dysfunction or death at Day 14 and Day 28. Persistent Organ Dysfunction is defined as the persistence of organ dysfunction requiring supportive technologies during the convalescent phase of critical illness and it is present when a patient has an ongoing requirement for vasopressors, dialysis, or mechanical ventilation at the outcome assessments time points, as defined by Heyland et al.; Persistent organ dysfunction plus death: a novel,composite outcome measure for critical care trials. Critical Care 2011, 15.
Time frame: day 14 and day 28
Population: Full Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm A | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Day 14 | 29 Participants |
| Treatment Arm A | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Day 28 | 25 Participants |
| Treatment Arm B | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Day 28 | 25 Participants |
| Treatment Arm B | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Day 14 | 37 Participants |
| Adrecizumab Overall | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Day 28 | 50 Participants |
| Adrecizumab Overall | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Day 14 | 66 Participants |
| Control Group | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Day 14 | 63 Participants |
| Control Group | Persistent Organ Dysfunction or Death at 14 and 28 Day Follow-up | Day 28 | 49 Participants |
Secondary
Sepsis Support Index (SSI)
Sepsis Support Index (SSI) at 28 day follow-up Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome.
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | Sepsis Support Index (SSI) | 13.3 score on a scale | Standard Deviation 10.91 |
| Treatment Arm B | Sepsis Support Index (SSI) | 14.6 score on a scale | Standard Deviation 10.76 |
| Adrecizumab Overall | Sepsis Support Index (SSI) | 14.0 score on a scale | Standard Deviation 10.82 |
| Control Group | Sepsis Support Index (SSI) | 12.8 score on a scale | Standard Deviation 11.14 |
Secondary
Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time
Sequential Organ Failure Assessment (SOFA) Score: SOFA score change at Day 3 - baseline, delta = difference between maximum and minimum score during ICU stay, mean/maximum/total daily score during ICU stay, SOFA-3 (score limited to cardiovascular, respiratory and renal function). Measured at baseline and Day 3. SOFA score: Minimum possible score is 0, maximum is 24. A higher score meas a worse outcome. Measured at baseline, Day 2 to Day 28. SOFA-3 score: Minimum possible score is 0, maximum is 12. A higher score meas a worse outcome. Measured at baseline, Day 2 to Day 28.
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA change | -0.9 score on a scale | Standard Deviation 4.77 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 maximum score | 7.2 score on a scale | Standard Deviation 2.14 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 change | -1.7 score on a scale | Standard Deviation 2.77 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 Delta score | 3.5 score on a scale | Standard Deviation 1.96 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA Delta score | 4.2 score on a scale | Standard Deviation 2.5 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA maximum score | 10.2 score on a scale | Standard Deviation 3.77 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 total score | 44.2 score on a scale | Standard Deviation 42.36 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA mean score | 7.957 score on a scale | Standard Deviation 3.7546 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 mean score | 8.909 score on a scale | Standard Deviation 6.5681 |
| Treatment Arm A | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA total score | 38.9 score on a scale | Standard Deviation 33.69 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA maximum score | 10.8 score on a scale | Standard Deviation 4.46 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA mean score | 8.319 score on a scale | Standard Deviation 3.8129 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 maximum score | 7.2 score on a scale | Standard Deviation 2.6 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 change | -0.9 score on a scale | Standard Deviation 2.81 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA total score | 54.9 score on a scale | Standard Deviation 55.56 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 Delta score | 3.5 score on a scale | Standard Deviation 2.26 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA Delta score | 4.8 score on a scale | Standard Deviation 3.8 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 mean score | 9.336 score on a scale | Standard Deviation 7.2622 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 total score | 56.4 score on a scale | Standard Deviation 51.13 |
| Treatment Arm B | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA change | -0.2 score on a scale | Standard Deviation 4.87 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA total score | 47.1 score on a scale | Standard Deviation 46.78 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 mean score | 9.129 score on a scale | Standard Deviation 6.9118 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA change | -0.5 score on a scale | Standard Deviation 4.87 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA Delta score | 4.5 score on a scale | Standard Deviation 3.24 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA maximum score | 10.5 score on a scale | Standard Deviation 4.13 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA mean score | 8.143 score on a scale | Standard Deviation 3.7751 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 change | -1.3 score on a scale | Standard Deviation 2.8 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 Delta score | 3.5 score on a scale | Standard Deviation 2.11 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 maximum score | 7.2 score on a scale | Standard Deviation 2.38 |
| Adrecizumab Overall | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 total score | 50.6 score on a scale | Standard Deviation 47.4 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA total score | 44.1 score on a scale | Standard Deviation 48.59 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA mean score | 7.644 score on a scale | Standard Deviation 3.5105 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 total score | 44.3 score on a scale | Standard Deviation 46.45 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 maximum score | 6.8 score on a scale | Standard Deviation 2.61 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA maximum score | 9.7 score on a scale | Standard Deviation 3.94 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 mean score | 8.311 score on a scale | Standard Deviation 8.0551 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA Delta score | 3.8 score on a scale | Standard Deviation 3.16 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 change | -0.9 score on a scale | Standard Deviation 2.92 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA change | 0.3 score on a scale | Standard Deviation 5.33 |
| Control Group | Sequential Organ Failure Assessment (SOFA) Score : Composite Measure: SOFA Score and Its Changes Over Time | SOFA-3 Delta score | 3.1 score on a scale | Standard Deviation 2.5 |
Secondary
SSI and pSSI Excluding the Renal Component
Sepsis Support Index (SSI) and penalized Sepsis Support Index (pSSI) excluding the renal component. pSSI is a version of the SSI where mortality is given extra weight: Patients being alive during the 14 days' follow up will have an SSI ranging up to 14, while patients who died within that period will be assigned a score of 14 plus the number of days not being alive. Thus the SSI and pSSI score may range between zero and 28. A higher score means a worse outcome. The number of participants analyzed differs per row due to missing data.
Time frame: day 14 and day 28
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | SSI and pSSI Excluding the Renal Component | SSI Day 14 | 8.0 score on a scale | Standard Deviation 5.21 |
| Treatment Arm A | SSI and pSSI Excluding the Renal Component | pSSI Day 14 | 8.1 score on a scale | Standard Deviation 5.32 |
| Treatment Arm A | SSI and pSSI Excluding the Renal Component | pSSI Day 28 | 13.4 score on a scale | Standard Deviation 11.47 |
| Treatment Arm A | SSI and pSSI Excluding the Renal Component | SSI Day 28 | 12.9 score on a scale | Standard Deviation 11.03 |
| Treatment Arm B | SSI and pSSI Excluding the Renal Component | pSSI Day 28 | 14.5 score on a scale | Standard Deviation 10.92 |
| Treatment Arm B | SSI and pSSI Excluding the Renal Component | SSI Day 14 | 9.0 score on a scale | Standard Deviation 5.24 |
| Treatment Arm B | SSI and pSSI Excluding the Renal Component | SSI Day 28 | 14.3 score on a scale | Standard Deviation 10.8 |
| Treatment Arm B | SSI and pSSI Excluding the Renal Component | pSSI Day 14 | 9.0 score on a scale | Standard Deviation 5.24 |
| Adrecizumab Overall | SSI and pSSI Excluding the Renal Component | pSSI Day 28 | 14.0 score on a scale | Standard Deviation 11.17 |
| Adrecizumab Overall | SSI and pSSI Excluding the Renal Component | pSSI Day 14 | 8.6 score on a scale | Standard Deviation 5.28 |
| Adrecizumab Overall | SSI and pSSI Excluding the Renal Component | SSI Day 14 | 8.5 score on a scale | Standard Deviation 5.24 |
| Adrecizumab Overall | SSI and pSSI Excluding the Renal Component | SSI Day 28 | 13.6 score on a scale | Standard Deviation 10.9 |
| Control Group | SSI and pSSI Excluding the Renal Component | SSI Day 14 | 7.9 score on a scale | Standard Deviation 5.42 |
| Control Group | SSI and pSSI Excluding the Renal Component | SSI Day 28 | 12.6 score on a scale | Standard Deviation 11.17 |
| Control Group | SSI and pSSI Excluding the Renal Component | pSSI Day 14 | 7.9 score on a scale | Standard Deviation 5.43 |
| Control Group | SSI and pSSI Excluding the Renal Component | pSSI Day 28 | 12.9 score on a scale | Standard Deviation 11.39 |
Secondary
SSI Weighted for Mortality
Sepsis Support Index (SSI) Weighted for Mortality. Minimum value possible is 0, maximum value is 14. A higher score means a worse outcome.
Time frame: day 14
Population: Full Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | SSI Weighted for Mortality | 10.2 score on a scale | Standard Deviation 7.76 |
| Treatment Arm B | SSI Weighted for Mortality | 10.7 score on a scale | Standard Deviation 7.65 |
| Adrecizumab Overall | SSI Weighted for Mortality | 10.5 score on a scale | Standard Deviation 7.68 |
| Control Group | SSI Weighted for Mortality | 9.9 score on a scale | Standard Deviation 8.41 |
Secondary
Vasopressor Use (Drug, Duration)
Vasopressor use (drug, duration). Vasopressor use was recorded from admission to ICU at time point of diagnosis of septic shock and daily thereafter from day 1 through day 28 or discharge from ICU (whatever comes first).
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS | 0 days | Standard Deviation 0 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS EXCL. ANTIGLAUCOMA PREPARATIONS | 0 days | Standard Deviation 0 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS, COMBINATIONS EXCL. CORTICOSTEROIDS | 0 days | Standard Deviation 0 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS, PLAIN | 1.67 days | Standard Deviation 1.658 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | VASOPRESSIN AND ANALOGUES | 1.75 days | Standard Deviation 0.5 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | LOCAL HEMOSTATICS | 1.67 days | Standard Deviation 1.658 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | OTHER AGENTS FOR LOCAL ORAL TREATMENT | 1.67 days | Standard Deviation 1.658 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS IN GLAUCOMA THERAPY | 1.67 days | Standard Deviation 1.658 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | R03CA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.67 days | Standard Deviation 1.658 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | ADRENERGIC AND DOPAMINERGIC AGENTS | 3.00 days | Standard Deviation 1.767 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | HOMEOPATHIC PREPARATION | 1.67 days | Standard Deviation 1.658 |
| Treatment Arm A | Vasopressor Use (Drug, Duration) | R03AA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.67 days | Standard Deviation 1.658 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | R03CA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.50 days | Standard Deviation 0.837 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | OTHER AGENTS FOR LOCAL ORAL TREATMENT | 1.50 days | Standard Deviation 0.837 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | LOCAL HEMOSTATICS | 1.50 days | Standard Deviation 0.837 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | ADRENERGIC AND DOPAMINERGIC AGENTS | 3.18 days | Standard Deviation 2.183 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | PHOSPHODIESTERASE INHIBITORS | 0 days | Standard Deviation 0 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | VASOPRESSIN AND ANALOGUES | 3.00 days | Standard Deviation 1.673 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS, PLAIN | 1.50 days | Standard Deviation 0.837 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | R03AA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.50 days | Standard Deviation 0.837 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS IN GLAUCOMA THERAPY | 1.50 days | Standard Deviation 0.837 |
| Treatment Arm B | Vasopressor Use (Drug, Duration) | HOMEOPATHIC PREPARATION | 1.50 days | Standard Deviation 0.837 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | OTHER AGENTS FOR LOCAL ORAL TREATMENT | 1.60 days | Standard Deviation 1.352 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS, PLAIN | 1.60 days | Standard Deviation 1.352 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | PHOSPHODIESTERASE INHIBITORS | 0 days | Standard Deviation 0 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS, COMBINATIONS EXCL. CORTICOSTEROIDS | 0 days | Standard Deviation 0 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS | 0 days | Standard Deviation 0 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | ADRENERGIC AND DOPAMINERGIC AGENTS | 3.10 days | Standard Deviation 1.994 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | R03AA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.60 days | Standard Deviation 1.352 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | R03CA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.60 days | Standard Deviation 1.352 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | LOCAL HEMOSTATICS | 1.60 days | Standard Deviation 1.352 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | HOMEOPATHIC PREPARATION | 1.60 days | Standard Deviation 1.352 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS IN GLAUCOMA THERAPY | 1.60 days | Standard Deviation 1.352 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS EXCL. ANTIGLAUCOMA PREPARATIONS | 0 days | Standard Deviation 0 |
| Adrecizumab Overall | Vasopressor Use (Drug, Duration) | VASOPRESSIN AND ANALOGUES | 2.50 days | Standard Deviation 1.434 |
| Control Group | Vasopressor Use (Drug, Duration) | LOCAL HEMOSTATICS | 1.78 days | Standard Deviation 1.641 |
| Control Group | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS EXCL. ANTIGLAUCOMA PREPARATIONS | 0 days | Standard Deviation 0 |
| Control Group | Vasopressor Use (Drug, Duration) | R03CA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.78 days | Standard Deviation 1.641 |
| Control Group | Vasopressor Use (Drug, Duration) | AGENTS FOR TREATMENT OF HEMORRHOIDS AND ANAL FISSURES FOR TOPICAL USE | 0 days | Standard Deviation 0 |
| Control Group | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS, PLAIN | 1.70 days | Standard Deviation 1.567 |
| Control Group | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS USED AS DECONGESTANTS | 0 days | Standard Deviation 0 |
| Control Group | Vasopressor Use (Drug, Duration) | PHOSPHODIESTERASE INHIBITORS | 4.00 days | Standard Deviation 1.732 |
| Control Group | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS, COMBINATIONS EXCL. CORTICOSTEROIDS | 0 days | Standard Deviation 0 |
| Control Group | Vasopressor Use (Drug, Duration) | ADRENERGIC AND DOPAMINERGIC AGENTS | 3.34 days | Standard Deviation 2.512 |
| Control Group | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS IN GLAUCOMA THERAPY | 1.78 days | Standard Deviation 1.641 |
| Control Group | Vasopressor Use (Drug, Duration) | SYMPATHOMIMETICS | 0 days | Standard Deviation 0 |
| Control Group | Vasopressor Use (Drug, Duration) | OTHER AGENTS FOR LOCAL ORAL TREATMENT | 1.78 days | Standard Deviation 1.641 |
| Control Group | Vasopressor Use (Drug, Duration) | HOMEOPATHIC PREPARATION | 1.78 days | Standard Deviation 1.641 |
| Control Group | Vasopressor Use (Drug, Duration) | VASOPRESSIN AND ANALOGUES | 2.21 days | Standard Deviation 1.701 |
| Control Group | Vasopressor Use (Drug, Duration) | R03AA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.78 days | Standard Deviation 1.641 |
Secondary
Vasopressor Use (Drug, Highest Dose)
Vasopressor use (drug, highest dose). Vasopressor use was recorded from admission to ICU at time point of diagnosis of septic shock and daily thereafter from day 1 through day 28 or discharge from ICU (whatever comes first).
Time frame: 28 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | VASOPRESSIN AND ANALOGUES | 0.0324 μg/kg/min | Standard Deviation 0.02597 |
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | SYMPATHOMIMETICS, PLAIN | 1.1236 μg/kg/min | Standard Deviation 1.4476 |
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | R03AA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.1236 μg/kg/min | Standard Deviation 1.4476 |
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | R03CA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.1236 μg/kg/min | Standard Deviation 1.4476 |
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | SYMPATHOMIMETICS IN GLAUCOMA THERAPY | 1.1236 μg/kg/min | Standard Deviation 1.4476 |
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | HOMEOPATHIC PREPARATION | 1.1236 μg/kg/min | Standard Deviation 1.4476 |
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | OTHER AGENTS FOR LOCAL ORAL TREATMENT | 1.1236 μg/kg/min | Standard Deviation 1.4476 |
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | LOCAL HEMOSTATICS | 1.1236 μg/kg/min | Standard Deviation 1.4476 |
| Treatment Arm A | Vasopressor Use (Drug, Highest Dose) | ADRENERGIC AND DOPAMINERGIC AGENTS | 3.1414 μg/kg/min | Standard Deviation 7.89069 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | PHOSPHODIESTERASE INHIBITORS | 0 μg/kg/min | Standard Deviation 0 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | HOMEOPATHIC PREPARATION | 2.1319 μg/kg/min | Standard Deviation 1.53579 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | R03AA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 2.1319 μg/kg/min | Standard Deviation 1.53579 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | OTHER AGENTS FOR LOCAL ORAL TREATMENT | 2.1319 μg/kg/min | Standard Deviation 1.53579 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | LOCAL HEMOSTATICS | 2.1319 μg/kg/min | Standard Deviation 1.53579 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | ADRENERGIC AND DOPAMINERGIC AGENTS | 1.7307 μg/kg/min | Standard Deviation 2.03233 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | SYMPATHOMIMETICS, PLAIN | 2.1319 μg/kg/min | Standard Deviation 1.53579 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | SYMPATHOMIMETICS IN GLAUCOMA THERAPY | 2.1319 μg/kg/min | Standard Deviation 1.53579 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | R03CA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 2.1319 μg/kg/min | Standard Deviation 1.53579 |
| Treatment Arm B | Vasopressor Use (Drug, Highest Dose) | VASOPRESSIN AND ANALOGUES | 0 μg/kg/min | Standard Deviation 0 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | PHOSPHODIESTERASE INHIBITORS | 0 μg/kg/min | Standard Deviation 0 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | ADRENERGIC AND DOPAMINERGIC AGENTS | 2.4124 μg/kg/min | Standard Deviation 5.70006 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | R03CA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.5018 μg/kg/min | Standard Deviation 1.51582 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | SYMPATHOMIMETICS IN GLAUCOMA THERAPY | 1.5018 μg/kg/min | Standard Deviation 1.51582 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | HOMEOPATHIC PREPARATION | 1.5018 μg/kg/min | Standard Deviation 1.51582 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | R03AA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.5018 μg/kg/min | Standard Deviation 1.51582 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | OTHER AGENTS FOR LOCAL ORAL TREATMENT | 1.5018 μg/kg/min | Standard Deviation 1.51582 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | LOCAL HEMOSTATICS | 1.5018 μg/kg/min | Standard Deviation 1.51582 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | VASOPRESSIN AND ANALOGUES | 0.0289 μg/kg/min | Standard Deviation 0.02265 |
| Adrecizumab Overall | Vasopressor Use (Drug, Highest Dose) | SYMPATHOMIMETICS, PLAIN | 1.5018 μg/kg/min | Standard Deviation 1.51582 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | SYMPATHOMIMETICS, PLAIN | 1.9888 μg/kg/min | Standard Deviation 2.60114 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | LOCAL HEMOSTATICS | 1.9888 μg/kg/min | Standard Deviation 2.60114 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | R03CA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.9888 μg/kg/min | Standard Deviation 2.60114 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | VASOPRESSIN AND ANALOGUES | 0.0343 μg/kg/min | Standard Deviation 0.02434 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | SYMPATHOMIMETICS IN GLAUCOMA THERAPY | 1.9888 μg/kg/min | Standard Deviation 2.60114 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | ADRENERGIC AND DOPAMINERGIC AGENTS | 1.8276 μg/kg/min | Standard Deviation 4.8611 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | HOMEOPATHIC PREPARATION | 1.9888 μg/kg/min | Standard Deviation 2.60114 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | R03AA ALPHA- AND BETA-ADRENORECEPTOR AGONISTS | 1.9888 μg/kg/min | Standard Deviation 2.60114 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | OTHER AGENTS FOR LOCAL ORAL TREATMENT | 1.9888 μg/kg/min | Standard Deviation 2.60114 |
| Control Group | Vasopressor Use (Drug, Highest Dose) | PHOSPHODIESTERASE INHIBITORS | 3.7763 μg/kg/min | Standard Deviation 1.05962 |
Secondary
Vital Signs
Vital signs: heart rate (beat per minute) Change from baseline to Day 7.
Time frame: 7 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Vital Signs | Heart Rate Change Day 7 (Maximum) | 5.6 beats per minute | Standard Deviation 33.24 |
| Treatment Arm A | Vital Signs | Heart Rate Change Day 7 (Minimum) | -27.2 beats per minute | Standard Deviation 22.91 |
| Treatment Arm B | Vital Signs | Heart Rate Change Day 7 (Maximum) | 4.3 beats per minute | Standard Deviation 21.85 |
| Treatment Arm B | Vital Signs | Heart Rate Change Day 7 (Minimum) | -18.5 beats per minute | Standard Deviation 20.53 |
| Adrecizumab Overall | Vital Signs | Heart Rate Change Day 7 (Minimum) | -22.4 beats per minute | Standard Deviation 21.96 |
| Adrecizumab Overall | Vital Signs | Heart Rate Change Day 7 (Maximum) | 4.9 beats per minute | Standard Deviation 27.46 |
| Control Group | Vital Signs | Heart Rate Change Day 7 (Minimum) | -18.1 beats per minute | Standard Deviation 24.49 |
| Control Group | Vital Signs | Heart Rate Change Day 7 (Maximum) | 13.5 beats per minute | Standard Deviation 28.25 |
Secondary
Vital Signs - Blood Pressure
Vital signs: blood pressure - mean arterial pressure (MAP) mmHg Change from baseline to Day 7.
Time frame: 7 days
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm A | Vital Signs - Blood Pressure | MAP Change Day 7 (Maximum) | 29.5 mmHg | Standard Deviation 22.26 |
| Treatment Arm A | Vital Signs - Blood Pressure | MAP Change Day 7 (Minimum) | -9.6 mmHg | Standard Deviation 17.2 |
| Treatment Arm B | Vital Signs - Blood Pressure | MAP Change Day 7 (Minimum) | -6.5 mmHg | Standard Deviation 11.51 |
| Treatment Arm B | Vital Signs - Blood Pressure | MAP Change Day 7 (Maximum) | 28.2 mmHg | Standard Deviation 16.29 |
| Adrecizumab Overall | Vital Signs - Blood Pressure | MAP Change Day 7 (Maximum) | 28.8 mmHg | Standard Deviation 19.13 |
| Adrecizumab Overall | Vital Signs - Blood Pressure | MAP Change Day 7 (Minimum) | -7.9 mmHg | Standard Deviation 14.37 |
| Control Group | Vital Signs - Blood Pressure | MAP Change Day 7 (Maximum) | 31.7 mmHg | Standard Deviation 21.09 |
| Control Group | Vital Signs - Blood Pressure | MAP Change Day 7 (Minimum) | -8.7 mmHg | Standard Deviation 18.97 |
Other Pre-specified
In Sub-study Key Pharmacokinetic Parameter AUC is to be Determined in 80 Patients
systemic exposure : Area under the plasma concentration versus time curve (AUC). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration.
Time frame: 28 days
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameter AUC is to be Determined in 80 Patients | 4910.33 h*μg/mL | Standard Deviation 1222.414 |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameter AUC is to be Determined in 80 Patients | 11245.28 h*μg/mL | Standard Deviation 3462.585 |
Other Pre-specified
In Sub-study Key Pharmacokinetic Parameter Elimination Half-life is to be Determined in 80 Patients
elimination half-life (t½). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration.
Time frame: 28 days
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameter Elimination Half-life is to be Determined in 80 Patients | 206.48 h | Standard Deviation 43.809 |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameter Elimination Half-life is to be Determined in 80 Patients | 177.90 h | Standard Deviation 44.25 |
Other Pre-specified
In Sub-study Key Pharmacokinetic Parameters Peak Plasma Concentrations (Cmax) Are to be Determined in 80 Patients
peak plasma concentrations (Cmax). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration.
Time frame: 28 days
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Peak Plasma Concentrations (Cmax) Are to be Determined in 80 Patients | 38.193 μg/mL | Standard Deviation 10.3942 |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Peak Plasma Concentrations (Cmax) Are to be Determined in 80 Patients | 86.854 μg/mL | Standard Deviation 22.2438 |
Other Pre-specified
In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients
Time to Cmax (tmax) in hours (h)
Time frame: 28 days
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.42 h | 2 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.45 h | 0 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.25 h | 0 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.37 h | 1 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.47 h | 0 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.5 h | 17 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.57 h | 1 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.58 h | 2 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.67 h | 1 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.73 h | 0 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 2.5 h | 0 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 21.97 h | 0 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 24.75 h | 1 Participants |
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 25.12 h | 1 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 2.5 h | 1 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.42 h | 1 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.58 h | 2 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 24.75 h | 0 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.25 h | 1 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.67 h | 2 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.37 h | 0 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.45 h | 1 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 21.97 h | 1 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.47 h | 2 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.73 h | 1 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.5 h | 18 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 25.12 h | 0 Participants |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameters Time to Cmax (Tmax) Are to be Determined in 80 Patients | 0.57 h | 0 Participants |
Other Pre-specified
In Sub-study Key Pharmacokinetic Parameter Systemic Clearance is to be Determined in 80 Patients
systemic clearance (CL). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration.
Time frame: 28 days
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameter Systemic Clearance is to be Determined in 80 Patients | 0.0286 L/h | Standard Deviation 0.0079 |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameter Systemic Clearance is to be Determined in 80 Patients | 0.0280 L/h | Standard Deviation 0.00826 |
Other Pre-specified
In Sub-study Key Pharmacokinetic Parameter Volume of Distribution is to be Determined in 80 Patients
volume of distribution (V). Time points at which blood samples were taken prior IMP administration, at 30 min, 24 hrs, 48 hrs , 96 hrs, 144 hrs, 648 hrs after IMP administration.
Time frame: 28 days
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment Arm A | In Sub-study Key Pharmacokinetic Parameter Volume of Distribution is to be Determined in 80 Patients | 4.277 L | Standard Deviation 1.922 |
| Treatment Arm B | In Sub-study Key Pharmacokinetic Parameter Volume of Distribution is to be Determined in 80 Patients | 3.737 L | Standard Deviation 0.9427 |