Adrecizumab in Cardiogenic Shock (ACCOST-HH)

October 7, 2021 updated by: Dr. med. Mahir Karakas

Investigator-initiated, Placebo-controlled, Double-blind, Multi-center, Randomized Trial to Assess the Efficacy and Safety of Adrecizumab in Subjects With Cardiogenic Shock

Cardiogenic shock is a serious medical condition with high mortality and morbidity. This trial assesses safety, tolerability and efficacy of Adrecizumab on top of standard of care in patients with cardiogenic shock.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Despite optimal treatment the mortality in patients with cardiogenic shock still exceeds 50% and surviving patients mostly suffer from severe heart failure due to an impaired cardiac function.It is hypothesized, that Adrenomedullin is a key player in the (dys)-regulation of vascular integrity. Adrecizumab is the first-in-class humanized monoclonal anti-Adrenomedullin antibody, and acts as a long-lasting plasma Adrenomedullin enhancer stabilizing barrier function at a reasonable safety profile.When the anti-Adrenomedullin antibody Adrecizumab is administered in the blood circulation at high concentrations by far exceeding those of plasma Adrenomedullin, the compartmental distribution of Adrenomedullin is altered. Adrecizumab, an IgG with a molecular weight of more than 150 kDa, is too large to freely diffuse from the blood circulation to the interstitium. With its fast association kinetics Adrecizumab quickly binds to Adrenomedullin in the blood circulation and "pulls" Adrenomedullin, which has been initially located in the interstitium, from this compartment to the blood circulation. The more Adrecizumab is applied, the stronger is the "pulling" effect and the higher the resulting concentrations of Adrecizumab-bound Adrenomedullin in the blood circulation. The increase of Adrecizumab-bound Adrenomedullin in the blood circulation occurs within 5-15 minutes after administration of Adrecizumab, since it induces a translocation of preformed Adrenomedullin. As a consequence of this redistribution, the Adrenomedullin concentration in the interstitium decreases, and less Adrenomedullin is able to act on smooth muscle cells to exert its vasodilatative activity. In the progression to cardiogenic shock, when it comes to excessive vasodilation and hypotension, administration of Adrecizumab thus can reduce vasodilation by substracting excessive levels of interstitially located Adrenomedullin.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
150

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 12203
        • University of Berlin, Campus Benjamin-Franklin
      • Hamburg, Germany, 20246
        • University Heart Center Hamburg
      • Ulm, Germany, 89081
        • University of Ulm

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

-Hospitalization for Cardiogenic shock (at the discretion of the local investigator)

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 with at least one of the following:
  • Altered mental status
  • Cold, clammy skin
  • Urine output <30 ml/h

  • Serum lactate >2mmol/l

    • Age above 18 years at time of screening
    • Body weight below 150 kg at time of screening
    • Females/Males who agree to comply with the applicable contraceptive requirements of the protocol

Exclusion Criteria:

  • Cardiogenic shock due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate <35 beats per minute, or atrial fibrillation/ flutter with sustained ventricular response of >160 beats per minute
  • Cardiogenic shock due to left ventricular outflow obstruction, obstructive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area <0.8 cm2 or mean gradient >50 mmHg on prior or current echocardiogram), and severe mitral stenosis
  • Cardiogenic shock due to mechanical cause or severe bleeding
  • Cardiogenic shock due to untreated clinically significant CAD requiring revascularization
  • Resuscitation > 60 minutes
  • Severe pre-existing hepatic disease unrelated to cardiogenic shock
  • Severe pre-existing renal disease (dialysis) unrelated to cardiogenic shock etiology

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Adrecizumab on top of standard of care
8 mg/kg body weight Adrecizumab diluted in up to 100 mL saline as single dose infusion
Biological: Adrecizumab
Drip infusion over 60 minutes
PLACEBO_COMPARATOR: Placebo on top of standard of care
100 mL saline as single dose infusion
Drug: Placebo
Drip infusion over 60 minutes
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Need of cardiovascular organ support within the first 30 days
Time Frame: 30 days
Number of days through day 30 without need for cardiovascular organ support, including vasopressors, or mechanical support (VA-ECMO, Impella)
30 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
30-day-Mortality
Time Frame: 30 days
All-cause mortality
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Dr. med. Mahir Karakas

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 4, 2019

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 26, 2021

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 26, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 17, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 17, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 8, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 7, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Accost

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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