Clinical Trial Results:
Placebo-controlled, double-blind, randomized trial to assess the efficacy and safety of Adrecizumab against placebo in subjects with cardiogenic shock
Summary
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EudraCT number |
2018-002824-17 |
Trial protocol |
DE |
Global end of trial date |
24 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Oct 2022
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First version publication date |
22 Oct 2022
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Other versions |
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Summary report(s) |
Synopsis Clinical Study Report |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ACCOST-HH
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03989531 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
University Medical Center Hamburg-Eppendorf
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Sponsor organisation address |
Martinistrasse 52, Hamburg, Germany, 20246
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Public contact |
Mahir Karakas, University Medical Centre Hamburg-Eppendorf, 0049 40741057975, m.karakas@uke.de
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Scientific contact |
Mahir Karakas, University Medical Centre Hamburg-Eppendorf, 0049 40741057975, m.karakas@uke.de
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Jan 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
24 Apr 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
24 Apr 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
1) To assess safety and tolerability of Adrecizumab in patients with cardiogenic shock
2) To evaluate if improvement of vascular integrity with Adrecizumab is superior to placebo in reduction of morbidity endpoints in patients with cardiogenic shock
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Protection of trial subjects |
There is substantial need to improve therapeutic options in cardiogenic shock, and i.v. Adrecizumab appears a safe and promising approach for this condition. All necessary measures were taken to assure safety of the patients, e.g., by individualized treatment regime, application of investigational medicinal product (IMP) only on top of SOC, supervision, and timely study visits.
Adrecizumab emerged as a safe intervention with large impact on disease burden in cardiogenic shock. The risk for the participants in this trial was not beyond the usual risks associated with the natural course of the disease and were even lower, since a proven intervention scheme was used.
An emergency un-blinding procedure as well as a data monitoring and safety board (DSMB) was established to minimise the risk for the patients.
Patient insurance covered any damage resulting from patients’ participation in the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Mar 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 150
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Worldwide total number of subjects |
150
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EEA total number of subjects |
150
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
62
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From 65 to 84 years |
84
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85 years and over |
4
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Recruitment
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Recruitment details |
First patient first visit (FPFV) was performed on 05-APR-2019. In total, 150 patients have been enrolled at four study sites. Site 01: Universitätsklinikum Hamburg-Eppendorf: 108 patients, Site 02: Charité – Universitätsmedizin Berlin: 13 patients, Site 03: Universitätsklinikum Ulm: 23 patients, Site 04: Universitätsklinikum Mannheim: 6 patients | |||||||||
Pre-assignment
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Screening details |
• Hospitalization for cardiogenic shock Cardiogenic shock is usually defined as: - Systolic blood pressure < 90 mmHg > 30 min or inotropes required to maintain pressure > 90 mmHg during systole - Signs of left heart insufficiency and/or pulmonary congestion - Signs of impaired organ perfusion | |||||||||
Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor | |||||||||
Blinding implementation details |
Study sites had blinded staff members. All study related patient contact was through blinded staff members at the respective study sites.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Experimental intervention | |||||||||
Arm description |
Adrecizumab on top of standard of care | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Adrecizumab
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Investigational medicinal product code |
HAM8101
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Infusion , Intravenous use
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Dosage and administration details |
Patients randomized to Adrecizumab received a single dose of 8 mg/kg body weight on top of SOC. For drip infusion, it was diluted in 100 mL sterile 0.9% sodium chloride solution. Single infusion over 60 min.
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Arm title
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Control intervention | |||||||||
Arm description |
Placebo/ control substance (NaCl 0.9%) on top of standard of care | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Physiological saline (NaCl 0.9%)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Infusion , Intravenous use
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Dosage and administration details |
Administration of i.v. Placebo/ control substance (NaCl 0.9%) according to the dosing rules for Adrecizumab.
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Baseline characteristics reporting groups
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Reporting group title |
Experimental intervention
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Reporting group description |
Adrecizumab on top of standard of care | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control intervention
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Reporting group description |
Placebo/ control substance (NaCl 0.9%) on top of standard of care | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Experimental intervention
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Reporting group description |
Adrecizumab on top of standard of care | ||
Reporting group title |
Control intervention
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Reporting group description |
Placebo/ control substance (NaCl 0.9%) on top of standard of care |
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End point title |
Number of days through day 30 without need for cardiovascular organ support, including vasopressors, or mechanical support (VA-ECMO, Impella) | ||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
30 days
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Statistical analysis title |
Efficacy Data - Primary Endpoint | ||||||||||||
Statistical analysis description |
The primary endpoint, i.e. number of days within 30 days without need for ventilation, was analysed using an ANCOVA model with random group as factor and all stratification variables in the randomisation as covariates, namely age, sex, and type of underlying cardiogenic shock (acute myocardial infarction versus other entities). The treatment effect with corresponding 95% confidence interval and p-value will be presented.
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Comparison groups |
Experimental intervention v Control intervention
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Number of subjects included in analysis |
150
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.367 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
-1.69
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
-5.37 | ||||||||||||
upper limit |
2 |
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End point title |
Ventilation requirement | |||||||||
End point description |
Requirement and length of mechanical ventilation
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End point type |
Secondary
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End point timeframe |
90 days
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No statistical analyses for this end point |
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End point title |
All-cause death within 30 days | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days
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No statistical analyses for this end point |
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End point title |
Cardiovascular death within 30 days | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days
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No statistical analyses for this end point |
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End point title |
Length of stay at Intensive Care Unit/ Intermediate Care Unit/ Heart Failure Unit | ||||||||||||
End point description |
Length of stay at Intensive Care Unit/ Intermediate Care Unit/ Heart Failure Unit in hours after application of IMP up to a total of 30 days
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End point type |
Secondary
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End point timeframe |
30 days
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
90 days
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||
Dictionary version |
27
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Reporting groups
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Reporting group title |
Experimental intervention
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Reporting group description |
Adrecizumab on top of standard of care | ||||||||||||||||||||||||||||||
Reporting group title |
Control intervention
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Reporting group description |
Placebo/ control substance (NaCl 0.9%) on top of standard of care | ||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Apr 2021 |
The protocol was updated (Version 7.0, 22. JAN 2021):
• Synopsis
The information on the study duration has been adapted.
• Synopsis, 8.3 Secondary Endpoints
Four of the secondary endpoints are now defined as optional endpoints.
• Synopsis, 8.3 Secondary Endpoints
The synopsis was reconciled with the contents of the section Statistical Methods Planned in the Protocol and
Determination of Sample Size.
• Synopsis
Three notes have been added that describe in more detail the statistical analysis as defined in the Statistical
Analysis Plan.
• Synopsis, 9.7.2.1 Proposed Sample Size
The number of patients to be statistically evaluated was clarified. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |