Septic Shock
Conditions
Brief summary
The purpose of this trial is to investigate the potential of FE 202158 as a treatment which can stabilize blood pressure for treatment of patients in early septic shock.
Interventions
DRUGFE 202158
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form by the patient or a legal representative according to local regulations' * Man or women 18 years of age or older * Body weight below 115 kg for male patients and 100 kg for female patients * Proven or suspected infection * Septic shock, i.e. vasodilatory hypotension requiring vasopressor support * Willing to use an adequate barrier method or hormonal method of contraception, if not abstinent, from informed consent to one week after the end of infusion of study medication
Exclusion criteria
* Present or a history within the last 6 months of symptoms of acute coronary syndrome (myocardial infarction or unstable angina) * Known or suspected endocarditis * Hypovolaemia suspected on clinical grounds, e.g. cold extremities with delayed capillary filling, low cardiac filling pressure, marked systolic or pulse pressure variation or positive leg raising test * Known or suspected cardiac failure * Known or suspected infection with (HIV)-1, HIV-2, hepatitis B, or hepatitis C * Pregnancy or breastfeeding * Any cause of hypotension other than early septic shock * Use of vasopressin or terlipressin within 7 days prior to start of IMP infusion * Proven or suspected acute mesenteric ischemia, as judged by the investigator * Known episode of septic shock within 1 month prior to screening * Death anticipated within 24 hours, or due to the underlying disease within 3 months * Known past or current 2nd and 3rd degree AV-block without a well functioning pacemaker * Brain injury within current hospitalisation * Present hospitalisation with burn injury * Symptomatic peripheral vascular disease including Raynaud's syndrome * Previously included in this trial * Intake of an Investigational Medicinal Product (IMP) within the last 3 months (or longer if judged by the Investigator to possibly influence the outcome of the current study) * Known participation in another interventional clinical trial * Considered by the investigator to be unsuitable to participate in the trial for any other reason
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | Mean arterial pressure (MAP) was measured intra-arterially on a continuous basis. Success percentage of patients maintaining target/adequate MAP (\>60 mmHg) without norepinephrine is presented. |
| Cumulative Dose of FE 202158 | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | Cumulative dose of FE 202158 was calculated from Day 1 up to Day 7. |
| Infusion Rate of FE 202158 | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | Infusion rate of FE 202158 was presented from Day 1 up to Day 7. |
| Cumulative Dose of Norepinephrine | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Cumulative dose of norepinephrine was calculated from Day 1 up to Day 7. |
| Infusion Rate of Norepinephrine | Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Infusion rates and all changes in infusion rates of norepinephrine were recorded continuously during the 7 day maximum treatment period. |
| Time to Septic Shock Resolution | Day 1 up to Day 28 | The Kaplan-Meyer estimation of time to out of septic shock was estimated where time to (first) septic shock resolution was defined as time of end of infusion regimen. Intermittent off treatment periods were regarded as part of the shock duration. Time to all but one patient out of septic shock is presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Output | Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | The urinary output was recorded every 24 hours up to Day 7, or as long as the patient was in intensive care unit. |
| Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Day 1 up to Day 7, and at follow-up assessments performed 24-72 hours after end of IMP infusion | Significant changes for vital signs (blood pressure, heart rate, mean arterial pressure), electrocardiogram (ECG), and laboratory parameters (clinical chemistry, haematology, haemostasis, and urinary parameters). |
| Fluid Balance | Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points. | The fluid balance (accumulated input/output) was recorded in 24-hour collecting periods when the patient was in the intensive care unit and during the infusion of FE 202158. |
| Summary of Investigator Reported Outcomes | Day 1 up to Day 2 | Investigator reported outcome on FE 202158 performance. Answers were graded on a visual analogue scale (VAS) from 0 to 10, 0 being the worst and 10 being the best outcome. |
| Morbidity Assessment | Day 1 up to Day 28 | Percentage of all the Days alive and out/free of intensive care unit, hospital, dialysis, or ventilation within Day 28 were summarized. Patients dying before or at Day 28 were counted as zero. |
| Graded Morbidity | Day 1 up to Day 28 | Collection of data on graded morbidity was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital. |
| Mortality | Day 1 up to Day 28 | Collection of data on mortality was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital. |
Countries
Belgium, Denmark
Participant flow
Recruitment details
The patients were recruited at the respective intensive care units at four centers (3 in Belgium and 1 in Denmark) between 05 Jul 2012 to 15 Nov 2013.
Pre-assignment details
Of the 159 patients screened, 31 patients were randomised and 30 patients were dosed. One patient in the 3.75 ng/kg/min dose group did not receive any study treatment due to an adverse event (elevation of troponin) recorded prior to infusion.
Participants by arm
| Arm | Count |
|---|---|
| Infusion Regimen 1 FE 202158 0.1 mg/ml (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days. | 5 |
| Infusion Regimen 2 FE 202158 0.1 mg/ml (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5 ng/kg/min, adjustable up to 5.0 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days. | 7 |
| Infusion Regimen 3 FE 202158 0.1 mg/ml (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min adjustable up to a maximum of 7.5 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days. | 5 |
| Infusion Regimen 4 FE 202158 0.1 mg/ml (10 mM acetate buffer, pH 4) was administered at initial infusion rate of 2.5-3.75 ng/kg/min, allowed to be increased to a maximum of 7.5 ng/kg/min if needed, with a maximum duration of 1 hour, during the first 6 hours of infusion. After 1 hour, or beyond the initial 6 hours, the infusion rate could not exceed 3.75 ng/kg/min. Each patient received FE 202158 until recovered from the shock, however for not more than 7 days. | 13 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 1 | 3 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Infusion Regimen 1 | Infusion Regimen 2 | Infusion Regimen 3 | Infusion Regimen 4 | Total |
|---|---|---|---|---|---|
| Age, Continuous | 69.0 years STANDARD_DEVIATION 12.7 | 67.9 years STANDARD_DEVIATION 13.7 | 64.8 years STANDARD_DEVIATION 10.1 | 67.6 years STANDARD_DEVIATION 13.2 | 67.4 years STANDARD_DEVIATION 12.2 |
| Septic shock characteristic: Primary infection location Abdominal cavity | 1 patients | 5 patients | 3 patients | 6 patients | 15 patients |
| Septic shock characteristic: Primary infection location Lung | 1 patients | 1 patients | 0 patients | 1 patients | 3 patients |
| Septic shock characteristic: Primary infection location Other | 3 patients | 0 patients | 1 patients | 1 patients | 5 patients |
| Septic shock characteristic: Primary infection location Unknown | 0 patients | 0 patients | 0 patients | 1 patients | 1 patients |
| Septic shock characteristic: Primary infection location Urinary tract | 0 patients | 1 patients | 1 patients | 4 patients | 6 patients |
| Septic shock characteristic: Primary infection type Bacterial | 4 patients | 6 patients | 3 patients | 12 patients | 25 patients |
| Septic shock characteristic: Primary infection type Other | 1 patients | 0 patients | 1 patients | 0 patients | 2 patients |
| Septic shock characteristic: Primary infection type Unknown | 0 patients | 1 patients | 1 patients | 1 patients | 3 patients |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 2 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 3 Participants | 8 Participants | 20 Participants |
| Total Sequential Organ Failure Assessment Score | 11 Score on scale STANDARD_DEVIATION 3.32 | 10 Score on scale STANDARD_DEVIATION 2.31 | 8.8 Score on scale STANDARD_DEVIATION 3.19 | 9.31 Score on scale STANDARD_DEVIATION 3.01 | 9.67 Score on scale STANDARD_DEVIATION 2.88 |
| Weight | 66.6 kg STANDARD_DEVIATION 13.5 | 74.7 kg STANDARD_DEVIATION 17.7 | 81.3 kg STANDARD_DEVIATION 8 | 78.9 kg STANDARD_DEVIATION 15.3 | 76.3 kg STANDARD_DEVIATION 14.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 5 | 7 / 7 | 4 / 5 | 12 / 13 | 27 / 30 |
| serious Total, serious adverse events | 1 / 5 | 4 / 7 | 2 / 5 | 3 / 13 | 10 / 30 |
Outcome results
Primary
Cumulative Dose of FE 202158
Cumulative dose of FE 202158 was calculated from Day 1 up to Day 7.
Time frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 5 (Post 120 h) | 4523.9 ng/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 4 (Post 96 h) | 4523.9 ng/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 7 (Post 168 h) | 4523.9 ng/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 2 (Post 48 h) | 4523.9 ng/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 2 (Post 36 h) | 4463.9 ng/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 1 (Post 24 h) | 4217.4 ng/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 6 (Post 144 h) | 4523.9 ng/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 3 (Post 72 h) | 4523.9 ng/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 1 (Post 12 h) | 2451 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 3 (Post 72 h) | 11511.4 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 5 (Post 120 h) | 12865.3 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 4 (Post 96 h) | 12204.6 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 1 (Post 24 h) | 5502.2 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 1 (Post 12 h) | 3276.3 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 2 (Post 36 h) | 7535.9 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 7 (Post 168 h) | 13543.7 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 6 (Post 144 h) | 13543.7 ng/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of FE 202158 | Day 2 (Post 48 h) | 9185 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 3 (Post 72 h) | 7902 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 1 (Post 12 h) | 2946 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 1 (Post 24 h) | 4927.3 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 2 (Post 36 h) | 5842 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 2 (Post 48 h) | 6716 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 4 (Post 96 h) | 7999.8 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 5 (Post 120 h) | 7999.8 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 6 (Post 144 h) | 7999.8 ng/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of FE 202158 | Day 7 (Post 168 h) | 7999.8 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 5 (Post 120 h) | 6621.8 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 2 (Post 48 h) | 5225 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 2 (Post 36 h) | 4619.2 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 7 (Post 168 h) | 7003.7 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 6 (Post 144 h) | 6696.5 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 1 (Post 24 h) | 3818.8 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 4 (Post 96 h) | 6298.6 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 3 (Post 72 h) | 5860.1 ng/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of FE 202158 | Day 1 (Post 12 h) | 2377 ng/kg |
Primary
Cumulative Dose of Norepinephrine
Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Cumulative dose of norepinephrine was calculated from Day 1 up to Day 7.
Time frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed. One patient in the 7.5 ng/kg/min group started the vasopressor support without prior administration of norepinephrine, and MAP was adequately controlled as needed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 5 (Post 120 h) | 720.8 µg/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 4 (Post 96 h) | 720.8 µg/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 7 (Post 168 h) | 720.8 µg/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 2 (Post 48 h) | 720.8 µg/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 2 (Post 36 h) | 720.8 µg/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 1 (Post 24 h) | 720.8 µg/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 6 (Post 144 h) | 720.8 µg/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 3 (Post 72 h) | 720.8 µg/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 1 (Post 12 h) | 358.1 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 3 (Post 72 h) | 669.0 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 5 (Post 120 h) | 1039.5 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 4 (Post 96 h) | 829.6 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 1 (Post 24 h) | 338.0 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 1 (Post 12 h) | 172.1 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 2 (Post 36 h) | 406.2 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 7 (Post 168 h) | 1152.0 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 6 (Post 144 h) | 1152.0 µg/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 2 (Post 48 h) | 495.5 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 3 (Post 72 h) | 778.4 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 1 (Post 12 h) | 118.0 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 1 (Post 24 h) | 357.5 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 2 (Post 36 h) | 778.2 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 2 (Post 48 h) | 778.4 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 4 (Post 96 h) | 778.4 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 5 (Post 120 h) | 778.4 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 6 (Post 144 h) | 778.4 µg/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 7 (Post 168 h) | 778.4 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 5 (Post 120 h) | 307.8 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 2 (Post 48 h) | 232.8 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 2 (Post 36 h) | 197.8 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 7 (Post 168 h) | 311.1 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 6 (Post 144 h) | 307.8 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 1 (Post 24 h) | 149.5 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 4 (Post 96 h) | 303.1 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 3 (Post 72 h) | 279.1 µg/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Cumulative Dose of Norepinephrine | Day 1 (Post 12 h) | 73.1 µg/kg |
Primary
Infusion Rate of FE 202158
Infusion rate of FE 202158 was presented from Day 1 up to Day 7.
Time frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 4 (Post 96 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 6 (Post 144 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 5 (Post 120 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 2 (Post 48 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 7 (Post 168 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 2 (Post 36 h) | 0.23 ng/kg/min | Standard Deviation 0.47 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 1 (Post 24 h) | 0.94 ng/kg/min | Standard Deviation 1.88 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 3 (Post 72 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 1 (Post 12 h) | 3.25 ng/kg/min | Standard Deviation 1.29 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 3 (Post 72 h) | 0.82 ng/kg/min | Standard Deviation 2.02 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 7 (Post 168 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 4 (Post 96 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 6 (Post 144 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 5 (Post 120 h) | 0.99 ng/kg/min | Standard Deviation 2.21 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 2 (Post 36 h) | 2.66 ng/kg/min | Standard Deviation 2.27 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 1 (Post 12 h) | 4.13 ng/kg/min | Standard Deviation 2.09 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 2 (Post 48 h) | 2.51 ng/kg/min | Standard Deviation 2.29 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of FE 202158 | Day 1 (Post 24 h) | 3.39 ng/kg/min | Standard Deviation 2.37 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 5 (Post 120 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 6 (Post 144 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 7 (Post 168 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 2 (Post 36 h) | 2.08 ng/kg/min | Standard Deviation 2.77 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 2 (Post 48 h) | 1.79 ng/kg/min | Standard Deviation 3.57 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 3 (Post 72 h) | 0.61 ng/kg/min | Standard Deviation 1.22 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 1 (Post 24 h) | 1.59 ng/kg/min | Standard Deviation 2.19 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 4 (Post 96 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of FE 202158 | Day 1 (Post 12 h) | 3.08 ng/kg/min | Standard Deviation 2.56 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 7 (Post 168 h) | 0.33 ng/kg/min | Standard Deviation 1.08 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 1 (Post 12 h) | 2.43 ng/kg/min | Standard Deviation 1.41 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 1 (Post 24 h) | 1.39 ng/kg/min | Standard Deviation 1.65 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 2 (Post 36 h) | 1.25 ng/kg/min | Standard Deviation 1.76 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 2 (Post 48 h) | 0.69 ng/kg/min | Standard Deviation 1.28 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 4 (Post 96 h) | 0.33 ng/kg/min | Standard Deviation 1.08 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 3 (Post 72 h) | 0.39 ng/kg/min | Standard Deviation 1.08 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 5 (Post 120 h) | 0.00 ng/kg/min | Standard Deviation 0 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of FE 202158 | Day 6 (Post 144 h) | 0.00 ng/kg/min | Standard Deviation 0 |
Primary
Infusion Rate of Norepinephrine
Norepinephrine was infused as required to maintain the target mean arterial pressure, if the highest infusion rate allowed of experimental drug FE 202158 did not provide adequate vasopressor support. Infusion rates and all changes in infusion rates of norepinephrine were recorded continuously during the 7 day maximum treatment period.
Time frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed. One patient in the 7.5 ng/kg/min group started the vasopressor support without prior administration of norepinephrine, and MAP was adequately controlled as needed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 5 (Post 120 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 4 (Post 96 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 7 (Post 168 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 2 (Post 48 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 2 (Post 36 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 1 (Post 24 h) | 0.010 µg/kg/min | Standard Deviation 0.02 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 6 (144 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 3 (Post 72 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 1 (Post 12 h) | 0.341 µg/kg/min | Standard Deviation 0.691 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 3 (Post 72 h) | 0.120 µg/kg/min | Standard Deviation 0.27 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 5 (Post 120 h) | 0.172 µg/kg/min | Standard Deviation 0.385 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 4 (Post 96 h) | 0.184 µg/kg/min | Standard Deviation 0.411 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 1 (Post 24 h) | 0.222 µg/kg/min | Standard Deviation 0.402 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 1 (Post 12 h) | 0.281 µg/kg/min | Standard Deviation 0.444 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 2 (Post 36 h) | 0.049 µg/kg/min | Standard Deviation 0.101 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 7 (Post 168 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 6 (144 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Infusion Rate of Norepinephrine | Day 2 (Post 48 h) | 0.105 µg/kg/min | Standard Deviation 0.215 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 3 (Post 72 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 1 (Post 12 h) | 0.215 µg/kg/min | Standard Deviation 0.405 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 1 (Post 24 h) | 0.639 µg/kg/min | Standard Deviation 1.28 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 2 (Post 36 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 2 (Post 48 h) | 0.004 µg/kg/min | Standard Deviation 0.008 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 4 (Post 96 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 5 (Post 120 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 6 (144 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Infusion Rate of Norepinephrine | Day 7 (Post 168 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 5 (Post 120 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 2 (Post 48 h) | 0.057 µg/kg/min | Standard Deviation 0.188 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 2 (Post 36 h) | 0.061 µg/kg/min | Standard Deviation 0.171 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 7 (Post 168 h) | 0.006 µg/kg/min | Standard Deviation 0.021 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 6 (144 h) | 0.000 µg/kg/min | Standard Deviation 0 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 1 (Post 24 h) | 0.089 µg/kg/min | Standard Deviation 0.188 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 4 (Post 96 h) | 0.005 µg/kg/min | Standard Deviation 0.016 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 3 (Post 72 h) | 0.024 µg/kg/min | Standard Deviation 0.079 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Infusion Rate of Norepinephrine | Day 1 (Post 12 h) | 0.111 µg/kg/min | Standard Deviation 0.197 |
Primary
Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine
Mean arterial pressure (MAP) was measured intra-arterially on a continuous basis. Success percentage of patients maintaining target/adequate MAP (\>60 mmHg) without norepinephrine is presented.
Time frame: Day 1 up to Day 7 post-infusion (Data collected at Day 1 at 1, 2, 3, 4, 5, 6, 9, 12, 15, 18 and 24 h, Day 2 at 36 and 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 1 h) | 20.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 3 h) | 20.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 6 h) | 25.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 12 h) | 60.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 18 h) | 60.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 24 h) | 80.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 2 (Post 36 h) | 80.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 2 (Post 48 h) | 80.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 3 (Post 72 h) | 80.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 4 (Post 96 h) | 80.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 5 (Post 120 h) | 80.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 6 (Post 144 h) | 80.0 Percentage of patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 7 (Post 168 h) | 80.0 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 12 h) | 28.6 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 7 (Post 168 h) | 80.0 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 5 (Post 120 h) | 80.0 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 2 (Post 48 h) | 50.0 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 6 h) | 14.3 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 1 h) | 42.9 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 4 (Post 96 h) | 80.0 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 3 (Post 72 h) | 66.7 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 24 h) | 42.9 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 18 h) | 42.9 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 3 h) | 14.3 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 6 (Post 144 h) | 80.0 Percentage of patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 2 (Post 36 h) | 66.7 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 5 (Post 120 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 12 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 18 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 7 (Post 168 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 24 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 2 (Post 36 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 6 (Post 144 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 2 (Post 48 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 3 (Post 72 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 4 (Post 96 h) | 80.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 1 h) | 60.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 3 h) | 60.0 Percentage of patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 6 h) | 80.0 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 4 (Post 96 h) | 76.9 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 2 (Post 48 h) | 76.9 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 12 h) | 53.8 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 1 h) | 7.7 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 2 (Post 36 h) | 61.5 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 24 h) | 61.5 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 6 h) | 76.9 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 3 h) | 53.8 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 1 (Post 18 h) | 66.7 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 3 (Post 72 h) | 69.2 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 7 (Post 168 h) | 76.9 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 6 (Post 144 h) | 84.6 Percentage of patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Percentage of Patients Maintaining Target/Adequate Mean Arterial Pressure (MAP>60 mmHg) Without Norepinephrine | Day 5 (Post 120 h) | 84.6 Percentage of patients |
Primary
Time to Septic Shock Resolution
The Kaplan-Meyer estimation of time to out of septic shock was estimated where time to (first) septic shock resolution was defined as time of end of infusion regimen. Intermittent off treatment periods were regarded as part of the shock duration. Time to all but one patient out of septic shock is presented.
Time frame: Day 1 up to Day 28
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Time to Septic Shock Resolution | 3.75 ng/kg/min (n=5) | 23 Hours |
| Infusion Regimen 1: 3.75 ng/kg/Min | Time to Septic Shock Resolution | 5.0 ng/kg/min (n=7) | 75 Hours |
| Infusion Regimen 1: 3.75 ng/kg/Min | Time to Septic Shock Resolution | 7.5 ng/kg/min (n=5) | 37 Hours |
| Infusion Regimen 1: 3.75 ng/kg/Min | Time to Septic Shock Resolution | Modified 3.75 ng/kg/min (n=13) | 89 Hours |
Secondary
Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram
Significant changes for vital signs (blood pressure, heart rate, mean arterial pressure), electrocardiogram (ECG), and laboratory parameters (clinical chemistry, haematology, haemostasis, and urinary parameters).
Time frame: Day 1 up to Day 7, and at follow-up assessments performed 24-72 hours after end of IMP infusion
Population: The safety analysis set comprised of all allocated and dosed patients and were analyzed according to the actual dosing regimen received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on electrocardiogram | 0 patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on vital signs | 0 patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on lab parameters | 0 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on electrocardiogram | 0 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on vital signs | 0 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on lab parameters | 0 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on lab parameters | 0 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on vital signs | 0 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on electrocardiogram | 0 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on electrocardiogram | 0 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on vital signs | 0 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Adverse Effects on Lab Parameters, Vital Signs and Electrocardiogram | Patients with adverse effects on lab parameters | 0 patients |
Secondary
Fluid Balance
The fluid balance (accumulated input/output) was recorded in 24-hour collecting periods when the patient was in the intensive care unit and during the infusion of FE 202158.
Time frame: Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Fluid Balance | Day 6 (Post 144 h) | 84 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Fluid Balance | Day 7 (Post 168 h) | 90 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Fluid Balance | Day 3 (Post 72 h) | 75 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Fluid Balance | Day 4 (Post 96 h) | 76 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Fluid Balance | Day 1 (Post 24 h) | 50 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Fluid Balance | Day 5 (Post 120 h) | 80 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Fluid Balance | Day 2 (Post 48 h) | 69 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Fluid Balance | Day 2 (Post 48 h) | 128 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Fluid Balance | Day 1 (Post 24 h) | 72 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Fluid Balance | Day 5 (Post 120 h) | 209 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Fluid Balance | Day 3 (Post 72 h) | 173 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Fluid Balance | Day 4 (Post 96 h) | 189 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Fluid Balance | Day 6 (Post 144 h) | 209 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Fluid Balance | Day 7 (Post 168 h) | 220 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Fluid Balance | Day 2 (Post 48 h) | 96 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Fluid Balance | Day 7 (Post 168 h) | 98 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Fluid Balance | Day 6 (Post 144 h) | 88 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Fluid Balance | Day 4 (Post 96 h) | 107 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Fluid Balance | Day 3 (Post 72 h) | 115 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Fluid Balance | Day 1 (Post 24 h) | 62 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Fluid Balance | Day 5 (Post 120 h) | 90 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Fluid Balance | Day 7 (Post 168 h) | 78 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Fluid Balance | Day 1 (Post 24 h) | 61 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Fluid Balance | Day 2 (Post 48 h) | 75 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Fluid Balance | Day 3 (Post 72 h) | 72 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Fluid Balance | Day 4 (Post 96 h) | 68 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Fluid Balance | Day 5 (Post 120 h) | 69 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Fluid Balance | Day 6 (Post 144 h) | 76 mL/kg |
Secondary
Graded Morbidity
Collection of data on graded morbidity was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital.
Time frame: Day 1 up to Day 28
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Graded Morbidity | Alive and out of hospital | 2 patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Graded Morbidity | In hospital (not intensive care unit) | 1 patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Graded Morbidity | In intensive care unit | 1 patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Graded Morbidity | Dead | 1 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Graded Morbidity | In hospital (not intensive care unit) | 2 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Graded Morbidity | In intensive care unit | 1 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Graded Morbidity | Dead | 2 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Graded Morbidity | Alive and out of hospital | 0 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Graded Morbidity | In intensive care unit | 0 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Graded Morbidity | In hospital (not intensive care unit) | 2 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Graded Morbidity | Dead | 1 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Graded Morbidity | Alive and out of hospital | 2 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Graded Morbidity | Dead | 3 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Graded Morbidity | In hospital (not intensive care unit) | 4 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Graded Morbidity | Alive and out of hospital | 6 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Graded Morbidity | In intensive care unit | 0 patients |
Secondary
Morbidity Assessment
Percentage of all the Days alive and out/free of intensive care unit, hospital, dialysis, or ventilation within Day 28 were summarized. Patients dying before or at Day 28 were counted as zero.
Time frame: Day 1 up to Day 28
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Morbidity Assessment | Days alive and out of intensive care unit | 51.6 percentage of days within 28 days |
| Infusion Regimen 1: 3.75 ng/kg/Min | Morbidity Assessment | Days alive and out of hospital | 12.8 percentage of days within 28 days |
| Infusion Regimen 1: 3.75 ng/kg/Min | Morbidity Assessment | Days alive and free of dialysis | 60 percentage of days within 28 days |
| Infusion Regimen 1: 3.75 ng/kg/Min | Morbidity Assessment | Days alive and free of ventilation | 58.8 percentage of days within 28 days |
| Infusion Regimen 2: 5.0 ng/kg/Min | Morbidity Assessment | Days alive and out of hospital | 3.6 percentage of days within 28 days |
| Infusion Regimen 2: 5.0 ng/kg/Min | Morbidity Assessment | Days alive and free of dialysis | 38.6 percentage of days within 28 days |
| Infusion Regimen 2: 5.0 ng/kg/Min | Morbidity Assessment | Days alive and free of ventilation | 39.6 percentage of days within 28 days |
| Infusion Regimen 2: 5.0 ng/kg/Min | Morbidity Assessment | Days alive and out of intensive care unit | 31.4 percentage of days within 28 days |
| Infusion Regimen 3: 7.5 ng/kg/Min | Morbidity Assessment | Days alive and free of dialysis | 80 percentage of days within 28 days |
| Infusion Regimen 3: 7.5 ng/kg/Min | Morbidity Assessment | Days alive and out of hospital | 17.8 percentage of days within 28 days |
| Infusion Regimen 3: 7.5 ng/kg/Min | Morbidity Assessment | Days alive and free of ventilation | 75.6 percentage of days within 28 days |
| Infusion Regimen 3: 7.5 ng/kg/Min | Morbidity Assessment | Days alive and out of intensive care unit | 61.2 percentage of days within 28 days |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Morbidity Assessment | Days alive and free of ventilation | 73.9 percentage of days within 28 days |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Morbidity Assessment | Days alive and out of hospital | 26.2 percentage of days within 28 days |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Morbidity Assessment | Days alive and out of intensive care unit | 58.8 percentage of days within 28 days |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Morbidity Assessment | Days alive and free of dialysis | 76.7 percentage of days within 28 days |
Secondary
Mortality
Collection of data on mortality was performed on Day 28 in addition to the collection of data on time of stay in intensive care unit and hospital.
Time frame: Day 1 up to Day 28
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Mortality | Alive | 4 patients |
| Infusion Regimen 1: 3.75 ng/kg/Min | Mortality | Dead | 1 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Mortality | Dead | 2 patients |
| Infusion Regimen 2: 5.0 ng/kg/Min | Mortality | Alive | 3 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Mortality | Alive | 4 patients |
| Infusion Regimen 3: 7.5 ng/kg/Min | Mortality | Dead | 1 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Mortality | Alive | 10 patients |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Mortality | Dead | 3 patients |
Secondary
Summary of Investigator Reported Outcomes
Investigator reported outcome on FE 202158 performance. Answers were graded on a visual analogue scale (VAS) from 0 to 10, 0 being the worst and 10 being the best outcome.
Time frame: Day 1 up to Day 2
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Summary of Investigator Reported Outcomes | Onset of action adequate to reach target MAP | 4.4 Score on scale | Standard Deviation 3.78 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Summary of Investigator Reported Outcomes | MAP maintained within desired boundaries (Day 1) | 6.8 Score on scale | Standard Deviation 2.77 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Summary of Investigator Reported Outcomes | MAP maintained within desired boundaries (Day 2) | 10 Score on scale | Standard Deviation 0 |
| Infusion Regimen 1: 3.75 ng/kg/Min | Summary of Investigator Reported Outcomes | Confidence to use FE 202158 as primary treatment | 6.5 Score on scale | Standard Deviation 1.91 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Summary of Investigator Reported Outcomes | MAP maintained within desired boundaries (Day 1) | 3.86 Score on scale | Standard Deviation 2.67 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Summary of Investigator Reported Outcomes | MAP maintained within desired boundaries (Day 2) | 4 Score on scale | Standard Deviation 2.35 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Summary of Investigator Reported Outcomes | Confidence to use FE 202158 as primary treatment | 5.5 Score on scale | Standard Deviation 2.43 |
| Infusion Regimen 2: 5.0 ng/kg/Min | Summary of Investigator Reported Outcomes | Onset of action adequate to reach target MAP | 3.57 Score on scale | Standard Deviation 2.51 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Summary of Investigator Reported Outcomes | MAP maintained within desired boundaries (Day 2) | 8.75 Score on scale | Standard Deviation 1.26 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Summary of Investigator Reported Outcomes | MAP maintained within desired boundaries (Day 1) | 9 Score on scale | Standard Deviation 1.22 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Summary of Investigator Reported Outcomes | Confidence to use FE 202158 as primary treatment | 9.5 Score on scale | Standard Deviation 0.577 |
| Infusion Regimen 3: 7.5 ng/kg/Min | Summary of Investigator Reported Outcomes | Onset of action adequate to reach target MAP | 9.0 Score on scale | Standard Deviation 1.22 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Summary of Investigator Reported Outcomes | Confidence to use FE 202158 as primary treatment | 8.18 Score on scale | Standard Deviation 2.44 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Summary of Investigator Reported Outcomes | MAP maintained within desired boundaries (Day 1) | 7.69 Score on scale | Standard Deviation 3.66 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Summary of Investigator Reported Outcomes | Onset of action adequate to reach target MAP | 7.85 Score on scale | Standard Deviation 2.54 |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Summary of Investigator Reported Outcomes | MAP maintained within desired boundaries (Day 2) | 6.71 Score on scale | Standard Deviation 3.77 |
Secondary
Urinary Output
The urinary output was recorded every 24 hours up to Day 7, or as long as the patient was in intensive care unit.
Time frame: Day 1 up to Day 7 post-infusion (Data collected on Day 1 at 24 h, Day 2 at 48 h, Day 3 at 72 h, Day 4 at 96 h, Day 5 at 120 h, Day 6 at 144 h, and Day 7 at 168 h). Data is presented for specific time points.
Population: Full analysis set (FAS) was the primary dataset of interest. FAS comprised of all patients who were dosed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Infusion Regimen 1: 3.75 ng/kg/Min | Urinary Output | Day 1 (Post 24 h) | 24.9 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Urinary Output | Day 6 (Post 144 h) | 81.8 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Urinary Output | Day 5 (Post 120 h) | 74.3 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Urinary Output | Day 2 (Post 48 h) | 42.9 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Urinary Output | Day 7 (Post 168 h) | 82.0 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Urinary Output | Day 3 (Post 72 h) | 57.3 mL/kg |
| Infusion Regimen 1: 3.75 ng/kg/Min | Urinary Output | Day 4 (Post 96 h) | 68.0 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Urinary Output | Day 6 (Post 144 h) | 85.9 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Urinary Output | Day 4 (Post 96 h) | 58.8 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Urinary Output | Day 3 (Post 72 h) | 43.2 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Urinary Output | Day 5 (Post 120 h) | 73.3 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Urinary Output | Day 7 (Post 168 h) | 96.1 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Urinary Output | Day 2 (Post 48 h) | 31.0 mL/kg |
| Infusion Regimen 2: 5.0 ng/kg/Min | Urinary Output | Day 1 (Post 24 h) | 21.8 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Urinary Output | Day 4 (Post 96 h) | 100.5 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Urinary Output | Day 1 (Post 24 h) | 36.0 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Urinary Output | Day 2 (Post 48 h) | 55.9 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Urinary Output | Day 3 (Post 72 h) | 79.2 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Urinary Output | Day 5 (Post 120 h) | 125.2 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Urinary Output | Day 6 (Post 144 h) | 139.8 mL/kg |
| Infusion Regimen 3: 7.5 ng/kg/Min | Urinary Output | Day 7 (Post 168 h) | 144.7 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Urinary Output | Day 3 (Post 72 h) | 72.3 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Urinary Output | Day 7 (Post 168 h) | 115.1 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Urinary Output | Day 6 (Post 144 h) | 111.9 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Urinary Output | Day 2 (Post 48 h) | 48.1 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Urinary Output | Day 1 (Post 24 h) | 24.1 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Urinary Output | Day 5 (Post 120 h) | 106.2 mL/kg |
| Infusion Regimen 4: Modified 3.75 ng/kg/Min | Urinary Output | Day 4 (Post 96 h) | 94.0 mL/kg |