Acute Kidney Injury
Conditions
Keywords
SA-AKI, Sepsis, AKI, Recombinant Alkaline Phosphatase, recAP
Brief summary
The purpose of this study is to determine whether recombinant Alkaline Phosphatase (recAP) is effective and save, and to determine the most effective dose, in the treatment of patients with acute kidney injury caused by sepsis.
Detailed description
Design: Adaptive trial with two stages and interim analysis * Stage 1: four arms; three dose groups and placebo. n=30/arm. (n=120) * Interim analysis based on 120 subjects, with continued recruitment, adding 11 subjects to Stage 1 safety population (n=131): to evaluate safety and select dose for stage 2 * Stage 2: one dose group and placebo. N=85/arm. (n=170) Total n in the study: 301. Primary objectives * To investigate the effect of recAP on renal function (measured creatinine clearance D1-D7 period, incidence and duration of renal replacement therapy (RRT) over 28 days, eGFR at D60 and D90) and related clinical parameters (ICU stay, Hospital stay, Mechanical ventilation over 28 days, SOFA and SAPS2 scores 28 days) in patients with SA-AKI. * To determine effective therapeutic dose(s) of recAP. Secondary objectives * To investigate the safety and tolerability of recAP in patients with SA AKI. (assessed by independent Data Monitoring Board, adverse events over 90 days study period, laboratory values, ECG, physical examniations, vital signs, Anti Drug Antibodies) * To investigate the pharmacokinetic profile (PK) of recAP in a subset of patients (part 1, n=120) with SA AKI. (Population PK; AUC D1-7, Cmax, Cmin, Tmax, terminal T1/2) * To investigate the immunogenic potential of recAP in patients with SA AKI. (anti-drug antibodies at D14, D28, D60 and D90) * To investigate the effect on quality of life (using the EuroQol, EQ-5D) following study inclusion, at ICU discharge, and Day 90. Other objectives • To evaluate whether specific patient groups can be identified that benefit most from recAP treatment or patient groups that are non-responders
Interventions
BIOLOGICALrecAP
One hour infusions once daily for three days
OTHERPlacebo
1 hour IV infusion once daily for 3 days
Sponsors
PPD Development, LP
AM-Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Signed Informed Consent Form (patient, legal representative or independent investigator) 2. Age 18 to 85 years, inclusive 3. Is admitted to the ICU or Intermediate Care Unit 4. Has diagnosis of sepsis (\< 96 hrs prior to first study drug), according to criteria defined by the American College of Chest Physicians/Society of Critical Care Medicine: 1. Has a proven or strongly suspected bacterial infection. 2. Has at least 2 of 4 SIRS criteria 72 hrs \< screening and 96 hrs \< first study drug 5. First diagnosis of AKI: AKI Stage 1 or greater, according to the AKIN criteria (time-window adjusted): 1. Increase in serum creatinine \> 26.2 µmol/L (0.30 mg/dL) in 48 hrs prior to screening, or 2. Increase in serum creatinine to \> 150% (\> 1.5-fold) from reference creatinine value in 48 hrs prior to screening 3. Urinary output \< 0.5 mL/kg/h for \> 6 hours following adequate fluid resuscitation 6. Continuing AKI needs to be confirmed by a confirmative fluid corrected serum creatinine measure, or 7. When the AKI diagnosis was made according to the AKIN urine output criteria (urinary output \< 0.5 mL/kg/h for \> 6 hours), the oliguria or anuria should still meet the AKIN urine output criteria prior to randomization.
Exclusion criteria
1. Woman of childbearing potential with a positive pregnancy test, pregnant, or breastfeeding. 2. Weighs more than 115 kg (253 lb). 3. Has life support limitations. 4. Is known to be human immunodeficiency virus positive. 5. Has urosepsis. 6. Is already on dialysis (RRT) or anticipated to receive RRT within 24 hours after study drug dosing due to the underlying disease. 7. Is receiving immunosuppressant treatment or is on chronic high doses of steroids equivalent to prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant patients. Patients with septic shock treated with hydrocortisone (e.g., 3 × 100 mg) can be included. 8. Is expected to have rapidly fatal outcome (within 24 hours). 9. Has known, confirmed fungal sepsis. 10. Has advanced chronic liver disease, confirmed by a Child-Pugh score of 10 to 15. 11. Has acute pancreatitis with no established source of infection. 12. Has participated in another investigational study within 30 days prior to enrollment. 13. Is not expected to survive for 28 days due to medical conditions other than SA AKI, including cancer, end-stage cardiac disease, cardiac arrest requiring cardiopulmonary resuscitation or with pulseless electrical activity or asystole within the past 30 days, end stage lung disease, and end stage liver disease. 14. Has known prior history of Chronic Kidney Disease with a documented estimated Glomerular Filtration Rate (eGFR) \< 60 mL/min by Modification of Diet in Renal Disease MDRD or CKD-EPI formula, known GFR \< 60 mL/min, or a known history of persistent creatinine level \> 150 µmol/L (1.70 mg/dL) for reasons other than the current sepsis condition. 15. Has diagnosis of malaria or other parasite infections. 16. Has burns on \> 20% of body surface. 17. Has had AKI diagnosis according to inclusion criteria \> 24 hours prior to study drug administration. 18. Is anticipated to be treated with non-continuous RRT from Day 1 to Day 7. 19. During Day 1 to Day 7 continuous RRT is anticipated to be started or stopped not according to per protocol criteria. 20. The AKI is most likely attributable to other causes than sepsis, such as nephrotoxic drugs and renal perfusion-related. 21. Improvement in serum creatinine of at least 0.30 mg/dL or (26.2 µmol/L) prior to administration of the study drug. 22. Patients who use nephrotoxic medication and who fulfill the SA-AKI inclusion criteria at screening are not eligible if the use of this nephrotoxic medication is to continue when alternative, medically appropriate, non-nephrotoxic medication is available. 23. Has a history of known IV drug abuse. 24. Is an employee or family member of the investigator or study site personnel. 25. Has active hematological malignancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | 7 days | Primary endpoint is calculated as the average of the standardized endogenous creatinine clearance values over the first seven days between the placebo and 1.6 mg/kg recAP arm. Standardized endogenous creatinine clearance is assessed on each days from D1 to Day 7 during a 6 +/- 1 hour period and calculated in mL/min as the mean creatinine clearance over the period. The study started with 4 treatment arms of which 0.4 mg/kg recAP and the 0.8 mg/kg recAP were dropped after the interim analysis. The number of the patients in the dropped arm are respectively 30 and 32. Therefore the statistical analysis has been performed only on the placebo and 1.6 mg/kg group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Had Renal Replacement Therapy (RRT) During the Period Day 1 to Day 28, Inclusive | 28 days | During the study the days on Renal Replacement Therapy (RRT) was recorded for each patients. During the first 7 days of the study (D1 to D7 included), patients were only allowed to receive continuous RRT, thereafter patients were also allowed to receive intermittent RRT. Standardization of RRT was attempted by providing guidelines to start and stop RRT (see protocol). Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study. |
Other
| Measure | Time frame | Description |
|---|---|---|
| All-cause Mortality at Day 28 | Day 28 | Number of patients in the ITT set, who died in the period between day 1 to day 28. Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study. |
| All-cause Mortality at Day 90 | Day 90 | Number of patients in the ITT set, who died in the period between Day 1 and Day 90 Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study. |
| Number of Participants Meeting at Least One MAKE 60 Criteria | Day 60 | Make 60 is composed of patients that meet at least one of the following criteria at day 60: 1. had eGFR \< 60 mL/min (calculated by using the CKD-EPI formula) or 2. became dialysis dependent up to Day 60 or 3. died prior to Day 60 Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study. |
| Number of Patients Who Meet at Least One of the MAKE 90 Criteria | Day 90 | Make 90 includes patients who meet at least one of the following parameters at Day 90: 1. had eGFR \<60 ml/min at Day 90, estimated by the CKD-EPI formula based on a serum creatinine or 2. was dialysis dependent up to Day 90 or 3. was hospitalized for a new episode of acute kidney injury prior to Day 90 or 4. died, prior to Day 90 Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study. |
Countries
Austria, Belgium, Czechia, Finland, France, Germany, Ireland, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
Patients suffering sepsis associated acute kidney injury and admitted to the ICU were recruited from December 2014 to May 2017 in 10 European countries and the USA.53 Sites recruited patients. Sepsis diagnosis was established following the Sepsis-2 criteria and AKI diagnosis was established following the AKIN criteria.
Pre-assignment details
Patients should show a continuation of AKI measured by a confirmatory serum creatinine value, which did not decrease \> or = 0.3 mg/dL compared to the diagnostic serum creatinine value or by a continuation of urine output of \< 0.5 mg/kg/h for more than 6 hours.
Participants by arm
| Arm | Count |
|---|---|
| Placebo One hour IV infusion of placebo once daily for 3 consecutive days | 116 |
| 0.4 mg/kg (250 U/kg) recAP One hour IV infusions of 0.4 mg/kg recAP once daily for three consecutive days | 31 |
| 0.8 mg/kg (500 U/kg) recAP One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days | 32 |
| 1.6 mg/kg (1000 U/kg) recAP One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days | 111 |
| Total | 290 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 |
| Overall Study | Death | 31 | 8 | 5 | 16 |
| Overall Study | different, e.g adm other hospital | 12 | 3 | 3 | 10 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 3 | 4 |
Baseline characteristics
| Characteristic | Total | Placebo | 1.6 mg/kg (1000 U/kg) recAP | 0.8 mg/kg (500 U/kg) recAP | 0.4 mg/kg (250 U/kg) recAP |
|---|---|---|---|---|---|
| Age, Continuous | 67.0 years | 68.0 years | 65.0 years | 66.5 years | 67.0 years |
| AKI stage AKI Stage 1 | 217 Participants | 91 Participants | 81 Participants | 23 Participants | 22 Participants |
| AKI stage AKI Stage 2 | 43 Participants | 16 Participants | 17 Participants | 5 Participants | 5 Participants |
| AKI stage AKI Stage 3 | 24 Participants | 5 Participants | 11 Participants | 4 Participants | 4 Participants |
| APACHE II | 26.0 units on a scale | 26.0 units on a scale | 25.0 units on a scale | 26.0 units on a scale | 30.0 units on a scale |
| Bloodpressure Diastolic bloodpressure | 56.0 mmHg | 56.5 mmHg | 55.0 mmHg | 58.0 mmHg | 54.0 mmHg |
| Bloodpressure Systolic bloodpressure | 110 mmHg | 112.0 mmHg | 107.0 mmHg | 118.5 mmHg | 108.0 mmHg |
| BMI | 26.6 kg/m2 | 26.3 kg/m2 | 26.8 kg/m2 | 27.4 kg/m2 | 25.8 kg/m2 |
| Body temperature <36oC | 31 Participants | 11 Participants | 11 Participants | 5 Participants | 4 Participants |
| Body temperature >= 36oC and =< 38oC | 197 Participants | 76 Participants | 79 Participants | 22 Participants | 20 Participants |
| Body temperature >38oC | 57 Participants | 27 Participants | 18 Participants | 5 Participants | 7 Participants |
| eGFR | 31.8 mL/min | 37.5 mL/min | 29.7 mL/min | 25.6 mL/min | 27.2 mL/min |
| Endogenous Creatinine clearance Baseline | 27.9 mL/min | 31.8 mL/min | 24.1 mL/min | 26.0 mL/min | 14.4 mL/min |
| Endogenous Creatinine clearance Day 1 | 29.4 mL/min | 35.9 mL/min | 26.0 mL/min | 25.2 mL/min | 28.3 mL/min |
| Heart rate | 95.5 beats/min | 98.0 beats/min | 95.0 beats/min | 90.0 beats/min | 93.0 beats/min |
| Mechanical ventilation | 181 Participants | 68 Participants | 70 Participants | 20 Participants | 23 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not collected | 38 Participants | 16 Participants | 14 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 242 Participants | 95 Participants | 95 Participants | 27 Participants | 25 Participants |
| Region of Enrollment Austria | 26 participants | 11 participants | 11 participants | 2 participants | 2 participants |
| Region of Enrollment Belgium | 35 participants | 12 participants | 13 participants | 5 participants | 5 participants |
| Region of Enrollment Czechia | 13 participants | 3 participants | 5 participants | 3 participants | 2 participants |
| Region of Enrollment Finland | 16 participants | 6 participants | 6 participants | 3 participants | 1 participants |
| Region of Enrollment France | 38 participants | 16 participants | 14 participants | 4 participants | 4 participants |
| Region of Enrollment Germany | 9 participants | 4 participants | 5 participants | 0 participants | 0 participants |
| Region of Enrollment Ireland | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment Netherlands | 71 participants | 28 participants | 28 participants | 7 participants | 8 participants |
| Region of Enrollment Spain | 23 participants | 9 participants | 7 participants | 4 participants | 3 participants |
| Region of Enrollment United Kingdom | 31 participants | 12 participants | 11 participants | 3 participants | 5 participants |
| Region of Enrollment United States | 27 participants | 14 participants | 11 participants | 1 participants | 1 participants |
| Serum Creatinine | 1.9 mg/dL | 1.8 mg/dL | 2.0 mg/dL | 1.9 mg/dL | 2.3 mg/dL |
| Sex: Female, Male Female | 85 Participants | 32 Participants | 29 Participants | 16 Participants | 8 Participants |
| Sex: Female, Male Male | 205 Participants | 84 Participants | 82 Participants | 16 Participants | 23 Participants |
| SOFA score | 10.0 units on a scale | 10.0 units on a scale | 10.0 units on a scale | 9.0 units on a scale | 10.0 units on a scale |
| Urine output | 46.3 mL/h | 60.0 mL/h | 39.1 mL/h | 27.4 mL/h | 50.0 mL/h |
| Vasopressor/ionotropic therapy | 263 Participants | 103 Participants | 102 Participants | 30 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 33 / 112 | 10 / 38 | 6 / 35 | 19 / 109 |
| other Total, other adverse events | 111 / 112 | 35 / 38 | 31 / 35 | 103 / 109 |
| serious Total, serious adverse events | 56 / 112 | 18 / 38 | 11 / 35 | 47 / 109 |
Outcome results
Primary
Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7)
Primary endpoint is calculated as the average of the standardized endogenous creatinine clearance values over the first seven days between the placebo and 1.6 mg/kg recAP arm. Standardized endogenous creatinine clearance is assessed on each days from D1 to Day 7 during a 6 +/- 1 hour period and calculated in mL/min as the mean creatinine clearance over the period. The study started with 4 treatment arms of which 0.4 mg/kg recAP and the 0.8 mg/kg recAP were dropped after the interim analysis. The number of the patients in the dropped arm are respectively 30 and 32. Therefore the statistical analysis has been performed only on the placebo and 1.6 mg/kg group.
Time frame: 7 days
Population: ITT combined includes all patients randomized in part 1 and part 2 of the study, excluding patients recruited whilst the interim analysis is performed to treatment arms not selected for Part 2. Some values were discarded by the adjudication committee.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 1 + Part 2 | 45.6 mL/min |
| Placebo | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 2 | 44.51 mL/min |
| Placebo | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 1 | 41.35 mL/min |
| 0.4 mg/kg (250 U/kg) recAP | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 1 | 43.30 mL/min |
| 0.4 mg/kg (250 U/kg) recAP | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 1 + Part 2 | 46.95 mL/min |
| 0.8 mg/kg (500 U/kg) recAP | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 1 | 64.25 mL/min |
| 0.8 mg/kg (500 U/kg) recAP | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 1 + Part 2 | 63.54 mL/min |
| 1.6 mg/kg (1000 U/kg) recAP | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 1 + Part 2 | 55.1 mL/min |
| 1.6 mg/kg (1000 U/kg) recAP | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 1 | 61.10 mL/min |
| 1.6 mg/kg (1000 U/kg) recAP | Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7) | Part 2 | 51.76 mL/min |
Comparison: Analysis for Part 1p-value: 0.94995% CI: [-62.57, 29.5]ANOVA
Comparison: Analysis for Part 2p-value: 0.69195% CI: [-23.09, 13.8]ANOVA
Comparison: Combination of analysis results from Part 1 (see statistical Analysis 1) and Part 2 (see Statistical analysis 2)p-value: 0.896Inverse normal method
Secondary
Number of Participants Who Had Renal Replacement Therapy (RRT) During the Period Day 1 to Day 28, Inclusive
During the study the days on Renal Replacement Therapy (RRT) was recorded for each patients. During the first 7 days of the study (D1 to D7 included), patients were only allowed to receive continuous RRT, thereafter patients were also allowed to receive intermittent RRT. Standardization of RRT was attempted by providing guidelines to start and stop RRT (see protocol). Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study.
Time frame: 28 days
Population: ITT combined
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Who Had Renal Replacement Therapy (RRT) During the Period Day 1 to Day 28, Inclusive | 34 Participants |
| 0.4 mg/kg (250 U/kg) recAP | Number of Participants Who Had Renal Replacement Therapy (RRT) During the Period Day 1 to Day 28, Inclusive | 11 Participants |
| 0.8 mg/kg (500 U/kg) recAP | Number of Participants Who Had Renal Replacement Therapy (RRT) During the Period Day 1 to Day 28, Inclusive | 7 Participants |
| 1.6 mg/kg (1000 U/kg) recAP | Number of Participants Who Had Renal Replacement Therapy (RRT) During the Period Day 1 to Day 28, Inclusive | 40 Participants |
p-value: 0.2895% CI: [0.8, 2.4]Chi-squared
Other Pre-specified
All-cause Mortality at Day 28
Number of patients in the ITT set, who died in the period between day 1 to day 28. Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study.
Time frame: Day 28
Population: ITT set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | All-cause Mortality at Day 28 | 31 Participants |
| 0.4 mg/kg (250 U/kg) recAP | All-cause Mortality at Day 28 | 8 Participants |
| 0.8 mg/kg (500 U/kg) recAP | All-cause Mortality at Day 28 | 4 Participants |
| 1.6 mg/kg (1000 U/kg) recAP | All-cause Mortality at Day 28 | 16 Participants |
p-value: 0.0295% CI: [0.02, 0.23]Cochran-Mantel-Haenszel
Other Pre-specified
All-cause Mortality at Day 90
Number of patients in the ITT set, who died in the period between Day 1 and Day 90 Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study.
Time frame: Day 90
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | All-cause Mortality at Day 90 | 34 Participants |
| 0.4 mg/kg (250 U/kg) recAP | All-cause Mortality at Day 90 | 9 Participants |
| 0.8 mg/kg (500 U/kg) recAP | All-cause Mortality at Day 90 | 6 Participants |
| 1.6 mg/kg (1000 U/kg) recAP | All-cause Mortality at Day 90 | 19 Participants |
p-value: 0.0395% CI: [0.01, 0.23]Cochran-Mantel-Haenszel
Other Pre-specified
Number of Participants Meeting at Least One MAKE 60 Criteria
Make 60 is composed of patients that meet at least one of the following criteria at day 60: 1. had eGFR \< 60 mL/min (calculated by using the CKD-EPI formula) or 2. became dialysis dependent up to Day 60 or 3. died prior to Day 60 Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study.
Time frame: Day 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants Meeting at Least One MAKE 60 Criteria | 46 Participants |
| 0.4 mg/kg (250 U/kg) recAP | Number of Participants Meeting at Least One MAKE 60 Criteria | 13 Participants |
| 0.8 mg/kg (500 U/kg) recAP | Number of Participants Meeting at Least One MAKE 60 Criteria | 11 Participants |
| 1.6 mg/kg (1000 U/kg) recAP | Number of Participants Meeting at Least One MAKE 60 Criteria | 30 Participants |
p-value: 0.04595% CI: [1, 3.1]Regression, Logistic
Other Pre-specified
Number of Patients Who Meet at Least One of the MAKE 90 Criteria
Make 90 includes patients who meet at least one of the following parameters at Day 90: 1. had eGFR \<60 ml/min at Day 90, estimated by the CKD-EPI formula based on a serum creatinine or 2. was dialysis dependent up to Day 90 or 3. was hospitalized for a new episode of acute kidney injury prior to Day 90 or 4. died, prior to Day 90 Statistical analysis was only performed on the placebo and 1.6 mg/kg recAP arm due to the small number of patients treated with the doses of 0.4 mg/kg and 0.8 mg/kg recAP. Those two doses were dropped in part 2 of the study.
Time frame: Day 90
Population: ITT
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Patients Who Meet at Least One of the MAKE 90 Criteria | 46 Participants |
| 0.4 mg/kg (250 U/kg) recAP | Number of Patients Who Meet at Least One of the MAKE 90 Criteria | 13 Participants |
| 0.8 mg/kg (500 U/kg) recAP | Number of Patients Who Meet at Least One of the MAKE 90 Criteria | 10 Participants |
| 1.6 mg/kg (1000 U/kg) recAP | Number of Patients Who Meet at Least One of the MAKE 90 Criteria | 29 Participants |
p-value: 0.0395% CI: [1.06, 3.26]Regression, Logistic