Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43866   clinical trials with a EudraCT protocol, of which   7287   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    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
    EudraCT number
    		 2018-002824-17
    Trial protocol
    		 DE  
    Global end of trial date
    24 Apr 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Oct 2022
    First version publication date
    22 Oct 2022
    Other versions
    Summary report(s)
    		 Synopsis Clinical Study Report

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ACCOST-HH
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03989531
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    University Medical Center Hamburg-Eppendorf
    Sponsor organisation address
    Martinistrasse 52, Hamburg, Germany, 20246
    Public contact
    Mahir Karakas, University Medical Centre Hamburg-Eppendorf, 0049 40741057975, m.karakas@uke.de
    Scientific contact
    Mahir Karakas, University Medical Centre Hamburg-Eppendorf, 0049 40741057975, m.karakas@uke.de
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Jan 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Apr 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Apr 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    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
    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.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Mar 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 150
    Worldwide total number of subjects
    150
    EEA total number of subjects
    150
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    62
    From 65 to 84 years
    84
    85 years and over
    4

    Subject disposition

    		 Close Top of page
    Recruitment
    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
    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
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    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.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Experimental intervention
    Arm description
    		 Adrecizumab on top of standard of care
    Arm type
    		 Experimental

    Investigational medicinal product name
    Adrecizumab
    Investigational medicinal product code
    HAM8101
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion , Intravenous use
    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.

    Arm title
    		 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%)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Infusion , Intravenous use
    Dosage and administration details
    Administration of i.v. Placebo/ control substance (NaCl 0.9%) according to the dosing rules for Adrecizumab.

    Number of subjects in period 1
    		Experimental intervention Control intervention
    Started
    77
    73
    Completed
    77
    73

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Experimental intervention
    Reporting group description
    		 Adrecizumab on top of standard of care

    Reporting group title
    Control intervention
    Reporting group description
    		 Placebo/ control substance (NaCl 0.9%) on top of standard of care

    Reporting group values
    		 Experimental intervention Control intervention Total
    Number of subjects
    		 77 73 150
    Age categorical
    Units: Subjects
        Adults ≤ 65 years
    		 31 31 62
        Adults > 65 years
    		 46 42 88
    Gender categorical
    Units: Subjects
        Female
    		 17 14 31
        Male
    		 60 59 119
    Type of un-derlying cardio-genic shock
    Units: Subjects
        Acute Myocardial Infarction
    		 37 36 73
        other entities
    		 40 37 77

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Experimental intervention
    Reporting group description
    		 Adrecizumab on top of standard of care

    Reporting group title
    Control intervention
    Reporting group description
    		 Placebo/ control substance (NaCl 0.9%) on top of standard of care

    Primary: Number of days through day 30 without need for cardiovascular organ support, including vasopressors, or mechanical support (VA-ECMO, Impella)

    		 Close Top of page
    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
    End point type
    Primary
    End point timeframe
    30 days
    End point values
    		 Experimental intervention Control intervention
    Number of subjects analysed
    77
    73
    Units: Days
        number (not applicable)
    12.37
    14.05
    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.
    Comparison groups
    Experimental intervention v Control intervention
    Number of subjects included in analysis
    150
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.367
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.37
         upper limit
    		 2

    Secondary: Ventilation requirement

    		 Close Top of page
    End point title
    		 Ventilation requirement
    End point description
    Requirement and length of mechanical ventilation
    End point type
    Secondary
    End point timeframe
    90 days
    End point values
    		 Experimental intervention Control intervention
    Number of subjects analysed
    77
    73
    Units: Number of subjects
    62
    61
    No statistical analyses for this end point

    Secondary: All-cause death within 30 days

    		 Close Top of page
    End point title
    		 All-cause death within 30 days
    End point description
    End point type
    Secondary
    End point timeframe
    30 days
    End point values
    		 Experimental intervention Control intervention
    Number of subjects analysed
    77
    73
    Units: patients
    31
    29
    No statistical analyses for this end point

    Secondary: Cardiovascular death within 30 days

    		 Close Top of page
    End point title
    		 Cardiovascular death within 30 days
    End point description
    End point type
    Secondary
    End point timeframe
    30 days
    End point values
    		 Experimental intervention Control intervention
    Number of subjects analysed
    77
    73
    Units: patients
    25
    25
    No statistical analyses for this end point

    Secondary: Length of stay at Intensive Care Unit/ Intermediate Care Unit/ Heart Failure Unit

    		 Close Top of page
    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
    End point type
    Secondary
    End point timeframe
    30 days
    End point values
    		 Experimental intervention Control intervention
    Number of subjects analysed
    77
    73
    Units: Hours
        arithmetic mean (full range (min-max))
    14.79 (12.3 to 17.27)
    15.36 (12.83 to 17.90)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    90 days
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27
    Reporting groups
    Reporting group title
    Experimental intervention
    Reporting group description
    		 Adrecizumab on top of standard of care

    Reporting group title
    Control intervention
    Reporting group description
    		 Placebo/ control substance (NaCl 0.9%) on top of standard of care

    Serious adverse events
    		 Experimental intervention Control intervention
    Total subjects affected by serious adverse events
         subjects affected / exposed
    59 / 77 (76.62%)
    57 / 73 (78.08%)
         number of deaths (all causes)
    37
    31
         number of deaths resulting from adverse events
    Cardiac disorders
    Cardiogenic shock
         subjects affected / exposed
    53 / 77 (68.83%)
    47 / 73 (64.38%)
         occurrences causally related to treatment / all
    0 / 20
    0 / 21
         deaths causally related to treatment / all
    0 / 20
    0 / 21
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Experimental intervention Control intervention
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    72 / 77 (93.51%)
    71 / 73 (97.26%)
    Investigations
    decreased glomerular filtration rate (GFR)
         subjects affected / exposed
    72 / 77 (93.51%)
    71 / 73 (97.26%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    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.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Tue Apr 30 02:44:28 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA