Cardiogenic ShockPhase 2/3ACCOST-HHNCT03989531
Adrecizumab in Cardiogenic Shock
A Phase 2/3 study testing Adrecizumab in people with Cardiogenic Shock and Endothelial Dysfunction, run by Dr. med. Mahir Karakas at 3 sites in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiogenic Shock, Endothelial Dysfunction
- What is being tested?
- Adrecizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 3 sitesGermany
- Study dates
- 4 Apr 2019to 26 Apr 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- -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
Show all 12Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Germany3 sites
University of Berlin, Campus Benjamin-Franklin
Berlin, 12203
University Heart Center Hamburg
Hamburg, 20246
University of Ulm
Ulm, 89081
About this study
Official title: 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.
Read the 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.
- Conditions
- Cardiogenic Shock, Endothelial Dysfunction
- Being tested
- Adrecizumab, Placebo
- Keywords
- Cardiogenic Shock, Adrecizumab, Vascular integrity, Endothelial dysfunction
- Medical subject headings
- Shock, Cardiogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdrecizumabBiological
Drip infusion over 60 minutes
PlaceboDrug
Also called Saline
Drip infusion over 60 minutes
| Study group | Role | What they receive |
|---|---|---|
| Adrecizumab on top of standard of care | Experimental | 8 mg/kg body weight Adrecizumab diluted in up to 100 mL saline as single dose infusion Receives: Biological: Adrecizumab |
| Placebo on top of standard of care | Placebo comparator | 100 mL saline as single dose infusion Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Need of cardiovascular organ support within the first 30 days
Number of days through day 30 without need for cardiovascular organ support, including vasopressors, or mechanical support (VA-ECMO, Impella)
Measured: 30 days
Secondary outcomes (1)
30-day-Mortality
All-cause mortality
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2019
- Study start4 Apr 2019
- Primary completion26 Apr 2021
- Study completion26 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiogenic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. med. Mahir Karakas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr. med. Mahir Karakas, Universitätsklinikum Hamburg-Eppendorf
- Investigators
- Mahir Karakas, MD, MBA, Principal investigator, University Heart Center Hamburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03989531
- Sponsor's protocol ID
- Accost
- Acronym
- ACCOST-HH
- Status last verified
- Oct 2021
- First submitted
- 17 Jun 2019
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Karakas M, Akin I, Burdelski C, Clemmensen P, Grahn H, Jarczak D, Kessler M, Kirchhof P, Landmesser U, Lezius S, Lindner D, Mebazaa A, Nierhaus A, Ocak A, Rottbauer W, Sinning C, Skurk C, Soffker G, Westermann D, Zapf A, Zengin E, Zeller T, Kluge S. Single-dose of adrecizumab versus placebo in acute cardiogenic shock (ACCOST-HH): an investigator-initiated, randomised, double-blinded, placebo-controlled, multicentre trial. Lancet Respir Med. 2022 Mar;10(3):247-254. doi: 10.1016/S2213-2600(21)00439-2. Epub 2021 Dec 8.
PubMed 34895483
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigator-initiated, Placebo-controlled, Double-blind, Multi-center, Randomized Trial to Assess the Efficacy and Safety of Adrecizumab in Subjects With Cardiogenic Shock
- ClinicalTrials.gov ID
- NCT03989531
- Acronym / sponsor ID
- ACCOST-HH / Accost
- Conditions
- Cardiogenic Shock, Endothelial Dysfunction
- Keywords
- Cardiogenic Shock, Adrecizumab, Vascular integrity, Endothelial dysfunction
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Dr. med. Mahir KarakasUniversity, hospital or other
- Study start
- 4 Apr 2019 (actual)
- Primary completion
- 26 Apr 2021 (actual)
- Study completion
- 26 Apr 2021 (actual)
- First posted
- 18 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adrecizumab on top of standard of care | Experimental | Biological: Adrecizumab8 mg/kg body weight Adrecizumab diluted in up to 100 mL saline as single dose infusion |
| Placebo on top of standard of care | Placebo comparator | Drug: Placebo100 mL saline as single dose infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- -Hospitalization for Cardiogenic shock (at the discretion of the local investigator)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdrecizumabDrip infusion over 60 minutes | Biological | Adrecizumab on top of standard of care |
| PlaceboAlso: SalineDrip infusion over 60 minutes | Drug | Placebo on top of standard of care |
Primary outcome
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)
1 secondary outcome
30-day-Mortality
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Derived from this study: PubMed 34895483Karakas M, Akin I, Burdelski C, Clemmensen P, Grahn H, Jarczak D, Kessler M, Kirchhof P, Landmesser U, Lezius S, Lindner D, Mebazaa A, Nierhaus A, Ocak A, Rottbauer W, Sinning C, Skurk C, Soffker G, Westermann D, Zapf A, Zengin E, Zeller T, Kluge S. Single-dose of adrecizumab versus placebo in acute cardiogenic shock (ACCOST-HH): an investigator-initiated, randomised, double-blinded, placebo-controlled, multicentre trial. Lancet Respir Med. 2022 Mar;10(3):247-254. doi: 10.1016/S2213-2600(21)00439-2. Epub 2021 Dec 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mahir Karakas, MD, MBA principal investigator
University Heart Center Hamburg
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Adrecizumab in people with Cardiogenic Shock and Endothelial Dysfunction, run by Dr. med. Mahir Karakas at 3 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Need of cardiovascular organ support within the first 30 days (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03989531, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021.