Cardiogenic shock MedDRA version: 20.0 Level: PT Classification code 10007625 Term: Cardiogenic shock System Organ Class: 10007541 - Cardiac disorders
Conditions
Interventions
Product Name: Adrecizumab
Product Code: HAM8101
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenou
Sponsors
University Medical Centre Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Hospitalization for Cardiogenic shock (at the discretion of the local investigator) Cardiogenic shock is usually defined as: 1.1 Systolic blood pressure 30 min or inotropes re-quired to maintain pressure > 90 mmHg during systole 1.2 Signs of left heart insufficiency and/ or pulmonary congestion 1.3 Signs of impaired organ perfusion with at least one of the fol-lowing: 1.3.1 Altered mental status 1.3.2 Cold, clammy skin 1.3.3 Urine output 2mmol/l 2. Age above 18 years at time of screening 3. Body weight below 150 kg at time of screening 4. Females/Males who agree to comply with the applicable contraceptive requirements of the protocol Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Cardiogenic shock due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate 160 beats per mi-nute 2. Cardiogenic shock due to left ventricular outflow obstruction, ob-structive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area 50 mmHg on prior or current echocardiogram), and severe mitral stenosis 3. Cardiogenic shock due to mechanical cause or severe bleeding 4. Cardiogenic shock due to untreated clinically significant CAD requiring revascularization 5. Resuscitation > 60 minutes 6. Severe pre-existing hepatic disease unrelated to cardiogenic shock 7. Severe pre-existing renal disease (dialysis) unrelated to cardiogenic shock etiology 8. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past year with a life expectancy less than 6 months 9. History of severe asthma, eczema, or atopic allergy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 ;Secondary Objective: not applicable;Primary end point(s): Primary safety endpoints • Rate of SAEs/ AEs/SUSARs in both arms (deemed to be related to IMP) • Mortality related to Adrecizumab • Interruption of infusion due to intolerability to Adrecizumab • New treatment-emergent adverse events (and changes in severity and frequency in these) related to Adrecizumab Primary efficacy endpoint: • Number of days through day 30 without need for cardiovascular organ support, including vasopressors, or mechanical support (VA-ECMO, Impella) ;Timepoint(s) of evaluation of this end point: Primary safety endpoints: Day 90 Primary efficacy endpoint: Day 30 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Requirement and length of mechanical ventilation 2. All-cause death within 30 days, and end of follow-up (90 days) 3. Cardiovascular death within 30 days, and end of follow-up (90 days) 4. 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 5. Worsening clinical condition 6. Peak and change (fold induction) in cardio-renal biomarkers from baseline to day 3 (including bioADM, MR-proADM, troponin, CRP, PenKid, NTproBNP, Lactate, DPP3) 7. Patient´s Global Assessment Questionnaire (PGA), Mini-Mental state exam questionnaire (MMSE) and Euroqol 5D questionnaire (EQ-5D) at discharge, day 30 and day 90 8. 6-minute walking test at days 30 and 90 9. Cumulative burden of arrhythmia until discharge 10. Rehospitalisation within 30 days and 90 days 11. Rehospitalisation for heart failure within 30 days and 90 days 12. An expanded safety composite event including death, MI, stroke, recurrent hospitalization, acute kidney injury, and gastrointestinal disorders will be collected, analysed and reported. The following secondary endpoints will only be assessed if the primary efficacy endpoint is met: a. Diuresis and natriuresis during and after administration of study drug b. Time to improvement in dyspnea by Likert scale c. Use of loopdiuretic and vasoactive agents d. Health economical calculation of disease-related costs during index hospitalization;Timepoint(s) of evaluation of this end point: 1., 5., 6., 9., 12., a., b., c., d. Day 90 2., 3., 7., 8., 10., 11. Baseline to day 30, baseline to day 90 4. Baseline to day 30 | — |
Countries
Germany
Contacts
Public ContactMahir Karakas
University Medical Centre Hamburg-Eppendorf
Outcome results
None listed