Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Safety, Tolerability, Efficacy and QoL Study of Human recAP in the Treatment of Patients With SA-AKI (STOP-AKI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02182440
Recruitment Status : Completed
First Posted : July 8, 2014
Results First Posted : March 23, 2020
Last Update Posted : March 23, 2020
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
AM-Pharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Acute Kidney Injury
Interventions Biological: recAP
Other: Placebo
Enrollment 301
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.
Arm/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Hide Arm/Group Description One hour IV infusion of Placebo once daily for three consecutive days One hour IV infusion of 0.4 mg/kg recAP once daily for three consecutive days One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days
Period Title: Overall Study
Started 116 39 35 111
ITTcombined [1] 116 31 32 111
ITTinterim [2] 30 31 32 29
Safety Population [3] 112 38 35 109
Completed 71 25 24 81
Not Completed 45 14 11 30
Reason Not Completed
Adverse Event             0             1             0             0
Death             31             8             5             16
Protocol Violation             0             1             0             0
Physician Decision             1             0             0             0
Withdrawal by Subject             1             1             3             4
different, e.g adm other hospital             12             3             3             10
[1]
Enrolled patients randomized to study drug, excl patients randomized during IA to 2 dropped doses
[2]
All randomized patients and included in the interim analysis (IA)
[3]
All randomized patients who received at least one dose of study drug
Arm/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP Total
Hide Arm/Group Description One hour IV infusion of placebo once daily for 3 consecutive days One hour IV infusions of 0.4 mg/kg recAP once daily for three consecutive days One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days Total of all reporting groups
Overall Number of Baseline Participants 116 31 32 111 290
Hide Baseline Analysis Population Description
ITT combined population
Age, Continuous  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
68.0
(61.0 to 75.0)
67.0
(61.0 to 72.0)
66.5
(62.5 to 72.0)
65.0
(57.0 to 73.0)
67.0
(59.0 to 73.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
Female
32
  27.6%
8
  25.8%
16
  50.0%
29
  26.1%
85
  29.3%
Male
84
  72.4%
23
  74.2%
16
  50.0%
82
  73.9%
205
  70.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
95
  81.9%
25
  80.6%
27
  84.4%
95
  85.6%
242
  83.4%
Black Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
4
   3.4%
0
   0.0%
0
   0.0%
1
   0.9%
5
   1.7%
Asian Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
1
   0.9%
2
   6.5%
0
   0.0%
1
   0.9%
4
   1.4%
Other Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
0
   0.0%
0
   0.0%
1
   3.1%
0
   0.0%
1
   0.3%
Not collected Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
16
  13.8%
4
  12.9%
4
  12.5%
14
  12.6%
38
  13.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Austria Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
11 2 2 11 26
Netherlands Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
28 8 7 28 71
Belgium Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
12 5 5 13 35
United States Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
14 1 1 11 27
Czechia Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
3 2 3 5 13
Ireland Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
1 0 0 0 1
Finland Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
6 1 3 6 16
United Kingdom Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
12 5 3 11 31
France Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
16 4 4 14 38
Spain Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
9 3 4 7 23
Germany Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
4 0 0 5 9
BMI   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Kg/m2
Number Analyzed 115 participants 30 participants 29 participants 110 participants 284 participants
26.3
(23.9 to 29.4)
25.8
(22.4 to 28.4)
27.4
(25.2 to 30.7)
26.8
(23.9 to 30.2)
26.6
(23.9 to 29.4)
[1]
Measure Analysis Population Description: BMI is composed of weight and height measurements. For some patients no Height was available
APACHE II   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 116 participants 31 participants 32 participants 110 participants 289 participants
26.0
(20.0 to 33.5)
30.0
(25.0 to 35.0)
26.0
(20.0 to 34.5)
25.0
(19.0 to 31.0)
26.0
(21.0 to 33.0)
[1]
Measure Description: Acute Physiology and Chronic Health Evaluation II score (APACHE II) is a severity-of-disease used in adults upon admission to the ICU. A score of 0 to 71 is calculated based on 12 routine measurements and the higher scores corresponds to a more severe disease state and a higher risk of mortality. Parameters included in the score are the patient's age, AaDO2 or PaO2 (depending on FiO2), temperature (rectal), Mean arterial pressure, pH arterial, Heart rate, Respiratory rate, Sodium (serum), Potassium (serum), Creatinine, Hematocrit, White blood cell count and Glasgow Coma Scale
[2]
Measure Analysis Population Description: One patient did not have an APACHE score at baseline
SOFA score   [1] [2] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 113 participants 29 participants 32 participants 108 participants 282 participants
10.0
(8.0 to 12.0)
10.0
(8.0 to 13.0)
9.0
(8.0 to 11.0)
10.0
(8.0 to 12.0)
10.0
(8.0 to 12.0)
[1]
Measure Description: Sequential Organ Failure Assessment score (SOFA score) is used to track a person's status during the stay in an intensive care unit (ICU) to determine the extent of a person's organ function or rate of failure. The SOFA score is composed of six different sub-scores, concerning respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. Each of the six subscores can have a maximal score of 4. The higher the score the more severe the organ dysfunction is (SOFA score ranges theoretically from 0-30).
[2]
Measure Analysis Population Description: Not all patients in ITT did had a baseline SOAFA score
Mechanical ventilation  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
68
  58.6%
23
  74.2%
20
  62.5%
70
  63.1%
181
  62.4%
Vasopressor/ionotropic therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
103
  88.8%
28
  90.3%
30
  93.8%
102
  91.9%
263
  90.7%
Heart rate  
Median (Inter-Quartile Range)
Unit of measure:  Beats/min
Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
98.0
(85.0 to 111.0)
93.0
(77.0 to 115.0)
90.0
(75.5 to 107.5)
95.0
(83.0 to 110.0)
95.5
(81.0 to 110.0)
Bloodpressure   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mmHg
Systolic bloodpressure Number Analyzed 116 participants 31 participants 32 participants 110 participants 289 participants
112.0
(101.5 to 131.5)
108.0
(100.0 to 119.0)
118.5
(96.0 to 131.0)
107.0
(95.0 to 119.0)
110
(98.0 to 123.0)
Diastolic bloodpressure Number Analyzed 116 participants 31 participants 32 participants 111 participants 290 participants
56.5
(51.0 to 63.5)
54.0
(49.0 to 62.0)
58.0
(54.0 to 62.0)
55.0
(49.0 to 62.0)
56.0
(50.0 to 62.0)
[1]
Measure Analysis Population Description: Lacking blood pressure results
Body temperature   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 114 participants 31 participants 32 participants 108 participants 285 participants
<36oC
11
   9.6%
4
  12.9%
5
  15.6%
11
  10.2%
31
  10.9%
>= 36oC and =< 38oC
76
  66.7%
20
  64.5%
22
  68.8%
79
  73.1%
197
  69.1%
>38oC
27
  23.7%
7
  22.6%
5
  15.6%
18
  16.7%
57
  20.0%
[1]
Measure Analysis Population Description: Missing data
eGFR   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mL/min
Number Analyzed 102 participants 27 participants 28 participants 98 participants 255 participants
37.5
(23.9 to 50.8)
27.2
(20.0 to 42.4)
25.6
(20.4 to 40.7)
29.7
(20.5 to 46.5)
31.8
(21.0 to 47.8)
[1]
Measure Analysis Population Description: Missing data
Endogenous Creatinine clearance   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mL/min
Baseline Number Analyzed 49 participants 10 participants 12 participants 46 participants 117 participants
31.8
(14.7 to 62.5)
14.4
(8.8 to 58.0)
26.0
(5.4 to 30.6)
24.1
(10.5 to 54.9)
27.9
(9.3 to 58.0)
Day 1 Number Analyzed 103 participants 30 participants 31 participants 102 participants 266 participants
35.9
(12.2 to 82.9)
28.3
(4.3 to 64.4)
25.2
(9.4 to 61.0)
26.0
(8.8 to 59.5)
29.4
(10.0 to 67.9)
[1]
Measure Analysis Population Description: Missing data
AKI stage   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
AKI Stage 1 Number Analyzed 112 participants 31 participants 32 participants 109 participants 284 participants
91
  81.3%
22
  71.0%
23
  71.9%
81
  74.3%
217
  76.4%
AKI Stage 2 Number Analyzed 112 participants 31 participants 32 participants 109 participants 284 participants
16
  14.3%
5
  16.1%
5
  15.6%
17
  15.6%
43
  15.1%
AKI Stage 3 Number Analyzed 112 participants 31 participants 32 participants 109 participants 284 participants
5
   4.5%
4
  12.9%
4
  12.5%
11
  10.1%
24
   8.5%
[1]
Measure Description: AKI stage defined 3 stages based on serum Creatinine measurements or urine output and provide a classification of the severity of the acute kidney injury (see KDIGO guidelines 2012 for more details). AKI Stage 3 being the most severe stage of kidney injury.
[2]
Measure Analysis Population Description: Missing data
Urine output   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mL/h
Number Analyzed 53 participants 13 participants 14 participants 50 participants 130 participants
60.0
(21.8 to 99.3)
50.0
(21.7 to 101.7)
27.4
(16.4 to 50.0)
39.1
(10.9 to 85.7)
46.3
(16.7 to 91.7)
[1]
Measure Analysis Population Description: Missing data
Serum Creatinine   [1] 
Median (Inter-Quartile Range)
Unit of measure:  mg/dL
Number Analyzed 113 participants 29 participants 32 participants 110 participants 284 participants
1.8
(1.3 to 2.4)
2.3
(1.5 to 2.8)
1.9
(1.5 to 2.8)
2.0
(1.4 to 2.8)
1.9
(1.4 to 2.6)
[1]
Measure Analysis Population Description: Missing data
1.Primary Outcome
Title Area Under the Time Corrected Endogenous Creatinine Clearance From Day 1 to Day 7 (AUC1-7)
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Hide Arm/Group Description:
One hour IV infusion of Placebo once daily for three consecutive days
One hour IV infusions of 0.4 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days
Overall Number of Participants Analyzed 106 30 32 108
Median (Inter-Quartile Range)
Unit of Measure: mL/min
Part 1 Number Analyzed 28 participants 29 participants 30 participants 29 participants
41.35
(19.00 to 130.15)
43.30
(16.40 to 93.30)
64.25
(14.20 to 104.00)
61.10
(6.80 to 93.50)
Part 2 Number Analyzed 77 participants 0 participants 0 participants 80 participants
44.51
(17.71 to 108.51)
51.76
(17.61 to 94.58)
Part 1 + Part 2 Number Analyzed 106 participants 30 participants 32 participants 108 participants
45.6
(17.7 to 112.4)
46.95
(6.58 to 88.40)
63.54
(8.07 to 96.77)
55.1
(15.0 to 93.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 1.6 mg/kg (1000 U/kg) recAP
Comments Analysis for Part 1
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.949
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -16.53
Confidence Interval (2-Sided) 95%
-62.57 to 29.50
Parameter Dispersion
Type: Standard Error of the Mean
Value: 19.243
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, 1.6 mg/kg (1000 U/kg) recAP
Comments Analysis for Part 2
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.691
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value -4.65
Confidence Interval (2-Sided) 95%
-23.09 to 13.80
Parameter Dispersion
Type: Standard Error of the Mean
Value: 9.305
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, 1.6 mg/kg (1000 U/kg) recAP
Comments Combination of analysis results from Part 1 (see statistical Analysis 1) and Part 2 (see Statistical analysis 2)
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.896
Comments [Not Specified]
Method Inverse normal method
Comments [Not Specified]
Method of Estimation Estimation Parameter Combined p-value
Estimated Value 0.896
Estimation Comments The p-values from Part 1 (see Statistical Analysis 1) and Part 2 (see Statistical Analysis 2) were combined to an overall p-value using the inverse normal method.
2.Secondary Outcome
Title Number of Participants Who Had Renal Replacement Therapy (RRT) During the Period Day 1 to Day 28, Inclusive
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT combined
Arm/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Hide Arm/Group Description:
One hour IV infusion of Placebo once daily for three consecutive days
One hour IV infusions of 0.4 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days
Overall Number of Participants Analyzed 116 31 32 111
Measure Type: Count of Participants
Unit of Measure: Participants
34
  29.3%
11
  35.5%
7
  21.9%
40
  36.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 1.6 mg/kg (1000 U/kg) recAP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.28
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
0.8 to 2.4
Estimation Comments [Not Specified]
3.Other Pre-specified Outcome
Title All-cause Mortality at Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT set
Arm/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Hide Arm/Group Description:
One hour IV infusion of placebo once daily for three consecutive days
One hour IV infusions of 0.4 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days
Overall Number of Participants Analyzed 116 31 32 111
Measure Type: Count of Participants
Unit of Measure: Participants
31
  26.7%
8
  25.8%
4
  12.5%
16
  14.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 1.6 mg/kg (1000 U/kg) recAP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
0.02 to 0.23
Estimation Comments [Not Specified]
4.Other Pre-specified Outcome
Title All-cause Mortality at Day 90
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Hide Arm/Group Description:
One hour IV infusion of Placebo once daily for three consecutive days
One hour IV infusions of 0.4 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days
Overall Number of Participants Analyzed 116 31 32 111
Measure Type: Count of Participants
Unit of Measure: Participants
34
  29.3%
9
  29.0%
6
  18.8%
19
  17.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 1.6 mg/kg (1000 U/kg) recAP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
0.01 to 0.23
Estimation Comments [Not Specified]
5.Other Pre-specified Outcome
Title Number of Participants Meeting at Least One MAKE 60 Criteria
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Hide Arm/Group Description:
One hour IV infusion of Placebo once daily for three consecutive days
One hour IV infusions of 0.4 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days
Overall Number of Participants Analyzed 116 31 32 111
Measure Type: Count of Participants
Unit of Measure: Participants
46
  39.7%
13
  41.9%
11
  34.4%
30
  27.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 1.6 mg/kg (1000 U/kg) recAP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
1.0 to 3.1
Estimation Comments [Not Specified]
6.Other Pre-specified Outcome
Title Number of Patients Who Meet at Least One of the MAKE 90 Criteria
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Hide Arm/Group Description:
One hour IV infusion of Placebo once daily for three consecutive days
One hour IV infusions of 0.4 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days
One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days
Overall Number of Participants Analyzed 116 31 32 111
Measure Type: Count of Participants
Unit of Measure: Participants
46
  39.7%
13
  41.9%
10
  31.3%
29
  26.1%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, 1.6 mg/kg (1000 U/kg) recAP
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.03
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.85
Confidence Interval (2-Sided) 95%
1.06 to 3.26
Estimation Comments [Not Specified]
Time Frame Adverse events were collected from the time the patient signed the informed consent form until Day 28
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Hide Arm/Group Description One hour IV infusion of Placebo once daily for three consecutive days One hour IV infusion of 0.4 mg/kg recAP once daily for three consecutive days One hour IV infusions of 0.8 mg/kg recAP once daily for three consecutive days One hour IV infusions of 1.6 mg/kg recAP once daily for three consecutive days
All-Cause Mortality
Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   33/112 (29.46%)   10/38 (26.32%)   6/35 (17.14%)   19/109 (17.43%) 
Hide Serious Adverse Events
Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   56/112 (50.00%)   18/38 (47.37%)   11/35 (31.43%)   47/109 (43.12%) 
Blood and lymphatic system disorders         
Anaemia * 1  2/112 (1.79%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Disseminated intravascular coagulation * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Thrombocytopenia * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  2/109 (1.83%) 
Cardiac disorders         
Acute myocardial infarction * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Arterial fibrillation * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Cardiac arrest * 1  4/112 (3.57%)  0/38 (0.00%)  1/35 (2.86%)  4/109 (3.67%) 
Cardiac failure * 1  2/112 (1.79%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Cardiac failure acute * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Cardio-respiratory arrest * 1  0/112 (0.00%)  0/38 (0.00%)  1/35 (2.86%)  0/109 (0.00%) 
Cardiogenic shock * 1  2/112 (1.79%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Cardiovascular insufficiency * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Myocardiac infarction * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  2/109 (1.83%) 
Supraventricular tachycardia * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Ventricular fibrillation * 1  0/112 (0.00%)  0/38 (0.00%)  1/35 (2.86%)  0/109 (0.00%) 
Ventricular tachycardia * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Ear and labyrinth disorders         
Deafness unilateral * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Gastrointestinal disorders         
Acute abdomen * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Ascites * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Colonic pseudo-obstruction * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Duodenal perforation * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Gastric fistula * 1  0/112 (0.00%)  0/38 (0.00%)  1/35 (2.86%)  0/109 (0.00%) 
Gastric ulcer haemorrhage * 1  2/112 (1.79%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Gastrointestinal haemorrage * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  1/109 (0.92%) 
Ileus * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Incarcerated inguinal hernia * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Intestinal infarction * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Intestinal ischaemia * 1  2/112 (1.79%)  0/38 (0.00%)  1/35 (2.86%)  1/109 (0.92%) 
Intestinal obstruction * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Intestinal perforation * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  2/109 (1.83%) 
Intral abdominal haemorrhage * 1  0/112 (0.00%)  0/38 (0.00%)  1/35 (2.86%)  0/109 (0.00%) 
Ischemia enteritis * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Large intestinal haemorrhage * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Large intestine perforation * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Mesenteric vein thrombosis * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Rectal Haemorrhage * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Upper gastrointestinal haemorrhage * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
General disorders         
Astenia * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
General physical health deterioration * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Multiple organ dysfunction syndrome * 1  7/112 (6.25%)  2/38 (5.26%)  0/35 (0.00%)  5/109 (4.59%) 
Hepatobiliary disorders         
Cholestasis * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Gallbladder perforation * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Hepatic failure * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Hepatic haematoma * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Hepatorenal syndrome * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Infections and infestations         
Abdominal abscess * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Abdominal sepsis * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Abscess intestinal * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Bronchopulmonary aspergillosis * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Candida infection * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Cholecystitis infective * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Clostridium Difficile infection * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Gastroenteritis * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Iatrogenic infection * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Infectious pleural effusion * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Lower respiratory tract infection * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Lung abscess * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  2/109 (1.83%) 
Necrotising fasciitis * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  1/109 (0.92%) 
Necrotising soft tissue infection * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Peritoneal abscess * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Peritonitis * 1  1/112 (0.89%)  0/38 (0.00%)  1/35 (2.86%)  1/109 (0.92%) 
Pharyngeal abscess * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Pneumonia * 1  3/112 (2.68%)  0/38 (0.00%)  2/35 (5.71%)  4/109 (3.67%) 
Pneumonia herpes viral * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Postoperative wound infection * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Septic shock * 1  11/112 (9.82%)  2/38 (5.26%)  4/35 (11.43%)  3/109 (2.75%) 
Soft tissue infection * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Injury, poisoning and procedural complications         
Abdominal wound dehiscence * 1  1/112 (0.89%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Anastomic leak * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Intestinal anastomosis complication * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Post procedural haemorrhage * 1  0/112 (0.00%)  1/38 (2.63%)  1/35 (2.86%)  0/109 (0.00%) 
Procedural complication * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Wound necrosis * 1  0/112 (0.00%)  0/38 (0.00%)  1/35 (2.86%)  0/109 (0.00%) 
Investigations         
Electrocardiogram QT prolonged * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
General physical condition abnormal * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Metabolism and nutrition disorders         
Caxhexia * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Musculoskeletal and connective tissue disorders         
Connective tissue disorders fasciitis * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Nervous system disorders         
Cerebral haemorrhage * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Cerebrovascular accident * 1  0/112 (0.00%)  0/38 (0.00%)  1/35 (2.86%)  0/109 (0.00%) 
Depressed level of consciousness * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Haemorrhage intracranial * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Ischaemic stroke * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  1/109 (0.92%) 
Metabolic encepalopathy * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Neuromyopathy * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Sedation * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Subarachnoid haemorrhage * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Psychiatric disorders         
Confusional state * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Renal and urinary disorders         
Acute kidney injury * 1  1/112 (0.89%)  1/38 (2.63%)  0/35 (0.00%)  1/109 (0.92%) 
Renal failure * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Acute lung injury * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Acute pulmonary oedema * 1  0/112 (0.00%)  0/38 (0.00%)  1/35 (2.86%)  0/109 (0.00%) 
Acute respiratory distress syndrome * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Acute respiratory failure * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Chronic obstructive pulmonary disease * 1  0/112 (0.00%)  0/38 (0.00%)  1/35 (2.86%)  0/109 (0.00%) 
Epistaxis * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Hypoxia * 1  1/112 (0.89%)  2/38 (5.26%)  0/35 (0.00%)  0/109 (0.00%) 
Pulmonary congestion * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Pulmonary embolism * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Pulmonary haemorrhage * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Pulmonary oedema * 1  2/112 (1.79%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Respiratory arrest * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Respiratory distress * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Respiratory failure * 1  10/112 (8.93%)  4/38 (10.53%)  1/35 (2.86%)  4/109 (3.67%) 
Skin and subcutaneous tissue disorders         
Skin necrosis * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Vascular disorders         
Arterial haemorrhage * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Arterial insufficiency * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Capillary disorder * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  0/109 (0.00%) 
Circulatory collapse * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Peripheral artery thrombosis * 1  0/112 (0.00%)  1/38 (2.63%)  0/35 (0.00%)  0/109 (0.00%) 
Peripheral ischemia * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  2/109 (1.83%) 
Shock * 1  2/112 (1.79%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
Shock haemorrhage * 1  1/112 (0.89%)  0/38 (0.00%)  0/35 (0.00%)  1/109 (0.92%) 
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo 0.4 mg/kg (250 U/kg) recAP 0.8 mg/kg (500 U/kg) recAP 1.6 mg/kg (1000 U/kg) recAP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   111/112 (99.11%)   35/38 (92.11%)   31/35 (88.57%)   103/109 (94.50%) 
Blood and lymphatic system disorders         
Thrombocytosis * 1  1/112 (0.89%)  0/38 (0.00%)  3/35 (8.57%)  3/109 (2.75%) 
Cardiac disorders         
Arterial flutter * 1  1/112 (0.89%)  2/38 (5.26%)  2/35 (5.71%)  3/109 (2.75%) 
Bradycardia * 1  3/112 (2.68%)  2/38 (5.26%)  0/35 (0.00%)  1/109 (0.92%) 
Sinus tachycardia * 1  5/112 (4.46%)  1/38 (2.63%)  0/35 (0.00%)  7/109 (6.42%) 
Gastrointestinal disorders         
Abdominal Pain * 1  9/112 (8.04%)  0/38 (0.00%)  3/35 (8.57%)  3/109 (2.75%) 
Constipation * 1  13/112 (11.61%)  1/38 (2.63%)  3/35 (8.57%)  12/109 (11.01%) 
Diarrhoea * 1  12/112 (10.71%)  2/38 (5.26%)  3/35 (8.57%)  16/109 (14.68%) 
Ileus apralytic * 1  0/112 (0.00%)  0/38 (0.00%)  0/35 (0.00%)  7/109 (6.42%) 
Impaired gastric emptying * 1  8/112 (7.14%)  1/38 (2.63%)  2/35 (5.71%)  8/109 (7.34%) 
Nausea * 1  14/112 (12.50%)  4/38 (10.53%)  3/35 (8.57%)  13/109 (11.93%) 
Vomiting * 1  5/112 (4.46%)  3/38 (7.89%)  1/35 (2.86%)  6/109 (5.50%) 
Abdominal distension * 1  4/112 (3.57%)  2/38 (5.26%)  2/35 (5.71%)  4/109 (3.67%) 
General disorders         
Generalised oedemia * 1  5/112 (4.46%)  3/38 (7.89%)  2/35 (5.71%)  9/109 (8.26%) 
Multiple organ dysfunction syndrome * 1  7/112 (6.25%)  2/38 (5.26%)  0/35 (0.00%)  5/109 (4.59%) 
Oedema peripheral * 1  17/112 (15.18%)  4/38 (10.53%)  5/35 (14.29%)  21/109 (19.27%) 
Pain * 1  5/112 (4.46%)  0/38 (0.00%)  2/35 (5.71%)  1/109 (0.92%) 
Pyrexia * 1  7/112 (6.25%)  2/38 (5.26%)  3/35 (8.57%)  10/109 (9.17%) 
Infections and infestations         
Cellulitis * 1  1/112 (0.89%)  2/38 (5.26%)  0/35 (0.00%)  0/109 (0.00%) 
Fungal infection * 1  3/112 (2.68%)  2/38 (5.26%)  0/35 (0.00%)  1/109 (0.92%) 
Herpes simplex * 1  1/112 (0.89%)  3/38 (7.89%)  0/35 (0.00%)  1/109 (0.92%) 
Oral herpes * 1  1/112 (0.89%)  1/38 (2.63%)  2/35 (5.71%)  3/109 (2.75%) 
Injury, poisoning and procedural complications         
Wound dehiscence * 1  0/112 (0.00%)  0/38 (0.00%)  2/35 (5.71%)  3/109 (2.75%) 
Investigations         
Blood phosphorus decreased * 1  2/112 (1.79%)  2/38 (5.26%)  1/35 (2.86%)  3/109 (2.75%) 
Breath sound abnormal * 1  0/112 (0.00%)  1/38 (2.63%)  2/35 (5.71%)  1/109 (0.92%) 
Cardiac murmur * 1  1/112 (0.89%)  0/38 (0.00%)  2/35 (5.71%)  0/109 (0.00%) 
Haemoglobin decreased * 1  9/112 (8.04%)  2/38 (5.26%)  1/35 (2.86%)  8/109 (7.34%) 
Blood potassium decreased * 1  2/112 (1.79%)  0/38 (0.00%)  2/35 (5.71%)  2/109 (1.83%) 
Metabolism and nutrition disorders         
Hyperglycemia * 1  3/112 (2.68%)  2/38 (5.26%)  1/35 (2.86%)  7/109 (6.42%) 
Hyperkalaemia * 1  5/112 (4.46%)  2/38 (5.26%)  0/35 (0.00%)  6/109 (5.50%) 
Hypernatraemia * 1  10/112 (8.93%)  0/38 (0.00%)  1/35 (2.86%)  6/109 (5.50%) 
Hypoglycaemia * 1  1/112 (0.89%)  3/38 (7.89%)  3/35 (8.57%)  9/109 (8.26%) 
Hypokalaemia * 1  17/112 (15.18%)  5/38 (13.16%)  3/35 (8.57%)  14/109 (12.84%) 
Hypomagnesaemia * 1  4/112 (3.57%)  2/38 (5.26%)  0/35 (0.00%)  2/109 (1.83%) 
Hypophosphataemia * 1  4/112 (3.57%)  2/38 (5.26%)  1/35 (2.86%)  6/109 (5.50%) 
Metabolic acidosis * 1  3/112 (2.68%)  0/38 (0.00%)  2/35 (5.71%)  3/109 (2.75%) 
Metabolic alkalosis * 1  3/112 (2.68%)  0/38 (0.00%)  2/35 (5.71%)  3/109 (2.75%) 
Nervous system disorders         
Intensive care unit acquired weakness * 1  4/112 (3.57%)  1/38 (2.63%)  2/35 (5.71%)  5/109 (4.59%) 
Psychiatric disorders         
Agitation * 1  6/112 (5.36%)  2/38 (5.26%)  2/35 (5.71%)  13/109 (11.93%) 
Anxiety * 1  3/112 (2.68%)  3/38 (7.89%)  2/35 (5.71%)  3/109 (2.75%) 
Delirium * 1  20/112 (17.86%)  5/38 (13.16%)  5/35 (14.29%)  14/109 (12.84%) 
Insomnia * 1  10/112 (8.93%)  2/38 (5.26%)  2/35 (5.71%)  13/109 (11.93%) 
Disorientation * 1  0/112 (0.00%)  3/38 (7.89%)  1/35 (2.86%)  2/109 (1.83%) 
Respiratory, thoracic and mediastinal disorders         
Atelectasis * 1  5/112 (4.46%)  1/38 (2.63%)  1/35 (2.86%)  6/109 (5.50%) 
Dyspnoea * 1  8/112 (7.14%)  0/38 (0.00%)  1/35 (2.86%)  1/109 (0.92%) 
Hypoxia * 1  1/112 (0.89%)  3/38 (7.89%)  1/35 (2.86%)  1/109 (0.92%) 
Lung infiltration * 1  0/112 (0.00%)  0/38 (0.00%)  2/35 (5.71%)  0/109 (0.00%) 
Pleural effusion * 1  11/112 (9.82%)  3/38 (7.89%)  4/35 (11.43%)  14/109 (12.84%) 
Tachypnoea * 1  0/112 (0.00%)  2/38 (5.26%)  0/35 (0.00%)  0/109 (0.00%) 
Wheezing * 1  0/112 (0.00%)  0/38 (0.00%)  2/35 (5.71%)  0/109 (0.00%) 
Skin and subcutaneous tissue disorders         
Decubitus ulcer * 1  2/112 (1.79%)  1/38 (2.63%)  1/35 (2.86%)  9/109 (8.26%) 
Erythema * 1  3/112 (2.68%)  2/38 (5.26%)  2/35 (5.71%)  1/109 (0.92%) 
Skin discolouration * 1  0/112 (0.00%)  2/38 (5.26%)  0/35 (0.00%)  0/109 (0.00%) 
Vascular disorders         
Hypertension * 1  10/112 (8.93%)  2/38 (5.26%)  6/35 (17.14%)  14/109 (12.84%) 
Hypotension * 1  10/112 (8.93%)  5/38 (13.16%)  2/35 (5.71%)  6/109 (5.50%) 
Phlebitis * 1  2/112 (1.79%)  1/38 (2.63%)  2/35 (5.71%)  2/109 (1.83%) 
Haematoma * 1  5/112 (4.46%)  1/38 (2.63%)  2/35 (5.71%)  2/109 (1.83%) 
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: JAcques Arend MD, DiMD, Chief Medical Officer
Organization: AM-Pharma B.V.
Phone: +31302598836
EMail: j.arend@am-pharma.com
Layout table for additonal information
Responsible Party: AM-Pharma
ClinicalTrials.gov Identifier: NCT02182440    
Other Study ID Numbers: AP-recAP-AKI-02-01
2014-000761-40 ( EudraCT Number )
First Submitted: June 27, 2014
First Posted: July 8, 2014
Results First Submitted: November 5, 2018
Results First Posted: March 23, 2020
Last Update Posted: March 23, 2020