4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Adrecizumab in Cardiogenic Shock (ACCOST-HH)

Adrecizumab in Cardiogenic Shock (ACCOST-HH)

Study Description
Brief 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.

Condition or disease Intervention/treatment Phase
Cardiogenic Shock Endothelial Dysfunction Biological: Adrecizumab Drug: Placebo Phase 2 Phase 3

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
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : April 4, 2019
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : June 2020
Arms and Interventions
Arm Intervention/treatment
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 Name: Saline
Outcome Measures
Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 30-day-Mortality [ Time Frame: 30 days ]
    All-cause mortality


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Mahir Karakas, MD, MBA +4915222817493 m.karakas@uke.de

Locations
Layout table for location information
Germany
University of Berlin, Campus Benjamin-Franklin Not yet recruiting
Berlin, Germany, 12203
Contact: Carsten Skurk, MD         
University Heart Center Hamburg Recruiting
Hamburg, Germany, 20246
Contact: Mahir Karakas, MD, MBA    +4915222817493    m.karakas@uke.de   
University of Ulm Recruiting
Ulm, Germany, 89081
Contact: Mirjam Kessler, MD         
Sponsors and Collaborators
Dr. med. Mahir Karakas
Investigators
Layout table for investigator information
Principal Investigator: Mahir Karakas, MD, MBA University Heart Center Hamburg
Tracking Information
First Submitted Date  ICMJE June 17, 2019
First Posted Date  ICMJE June 18, 2019
Last Update Posted Date June 19, 2019
Actual Study Start Date  ICMJE April 4, 2019
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2019) 		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)
Original Primary Outcome Measures  ICMJE
 (submitted: June 17, 2019) 		Cardiovascular organ support [ Time Frame: 30 days ]
Number of days through day 30 without need for cardiovascular organ support, including vasopressors, or mechanical support (VA-ECMO, Impella)
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2019) 		30-day-Mortality [ Time Frame: 30 days ]
All-cause mortality
Original Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2019) 		Mortality [ Time Frame: 30 days ]
All-cause mortality
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Adrecizumab in Cardiogenic Shock
Official Title  ICMJE Investigator-initiated, Placebo-controlled, Double-blind, Multi-center, Randomized Trial to Assess the Efficacy and Safety of Adrecizumab in Subjects With Cardiogenic Shock
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Cardiogenic Shock
  • Endothelial Dysfunction
Intervention  ICMJE
  • Biological: Adrecizumab
    Drip infusion over 60 minutes
  • Drug: Placebo
    Drip infusion over 60 minutes
    Other Name: Saline
Study Arms  ICMJE
  • 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
    Intervention: Biological: Adrecizumab
  • Placebo Comparator: Placebo on top of standard of care
    100 mL saline as single dose infusion
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: June 17, 2019) 		150
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03989531
Other Study ID Numbers  ICMJE Accost
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Dr. med. Mahir Karakas, Universitätsklinikum Hamburg-Eppendorf
Study Sponsor  ICMJE Dr. med. Mahir Karakas
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mahir Karakas, MD, MBA University Heart Center Hamburg
PRS Account Universitätsklinikum Hamburg-Eppendorf
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯