A Phase II/III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Relaxin in Subjects with Acute Heart Failure

Phase 3

Completed

Conditions: acute decompensated heart failure
heart problems
10019280

Registration Number: NL-OMON36636

Lead Sponsor: Corthera Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 42

Inclusion Criteria

1. Able to provide written informed consent
2. Male or female >=18 years of age, with body weight <= 160 kg
3. Systolic blood pressure > 125 mmHg at the start of screening and at the end of screening
4. Hospitalized for AHF. AHF is defined as including all of the following measured at any time between presentation (including the emergency department [ED]) and the end of screening:
a. Dyspnea at rest or with minimal exertion
b. Pulmonary congestion on chest radiograph
c.BNP >= 350pg/mL or NT-pro-BNP >=1400 pg/mL
5. Able to be randomized within 16 hours from presentation to the hospital, including the ED
6. Received IV furosemide of at least 40 mg (or equivalent) at any time between admission to emergency services (either ambulance or hospital, including the ED) and the start of screening for the study
7. Impaired renal function defined as an estimated glomerular filtration rate (eGFR) on admission between 30-75 mL/min/1.73 m2, calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equation

Exclusion Criteria

1. Pregnant or breast-feeding women (women of child bearing potential must have the results of a negative pregnancy test recorded prior to study drug administration)
2. Administration of intravenous radiographic contrast agent within 72 hours prior to screening or acute contrast-induced nephropathy at the time of screening
3. Temperature >38°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment
4. Current (within 2 hours prior to screening) or planned (through the completion of study drug infusion) treatment with any IV therapies, including vasodilators (including nesiritide), positive inotropic agents and vasopressors, or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device), with the exception of IV nitrates at a dose of < 0.1 mg/kg/hr if the patient has a systolic BP > 150 mmHg at screening
5. Current or planned ultrafiltration, hemofiltration, or dialysis
6. Known significant pulmonary disease
7. Known significant valvular disease (including any of the following: severe aortic stenosis [AVA < 1.0 or mean gradient >50 on prior or current echocardiogram], severe aortic regurgitation, or severe mitral stenosis)
8. Any organ transplant recipient, or patient currently listed for transplant or admitted for any transplantation
9. Major surgery within 30 days
10. Hematocrit < 25% or blood transfusion in the prior 14 days or active, life-threatening GI bleeding or active menorrhagia or metrorrhagia
11. Major neurologic event, including cerebrovascular events, in the prior 60 days
12. Clinical diagnosis of acute coronary syndrome within 45 days prior to screening (including the present admission) as determined by both clinical and enzymatic criteria
13. Troponin >=3 times the upper limit of normal (including borderline/intermediate) between presentation and screening.
14. AHF due to significant arrhythmias (including any of the following: ventricular tachycardia, bradyarrhythmias with ventricular rate <45 beats per minute or any second or third degree AV block or atrial fibrillation/flutter with ventricular response of >120 beats per minute)
15. Acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (does not include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function)
16. Known hepatic impairment
17. Non-cardiac pulmonary edema, including suspected sepsis
18. Administration of an investigational drug or implantation of investigational device, or participation in another trial, within 30 days before screening or previous treatment with relaxin
19. Inability to follow instructions or comply with follow-up procedures
20. Known hypersensitivity to relaxin or similar substances or to any of the excipients

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The two primary efficacy endpoints for the Phase III RELAX-AHF are:<br /><br>1) Area Under the Curve (AUC) representing the change in patient-reported<br /><br>dyspnea from baseline measured by a 100-mm Visual Analog Scale (VAS) from<br /><br>baseline through Day 5<br /><br>2) Moderately or markedly better patient-reported dyspnea relative to the start<br /><br>of study drug on the 7-point Likert scale at 6, 12 and 24 hours (at all 3<br /><br>timepoints)<br /><br><br /><br>Safety will be assessed by comparing the relaxin group to the placebo group<br /><br>with regard to the frequency of adverse events, and changes in vital signs,<br /><br>physical examination findings, AHFrelated signs and symptoms, and clinical<br /><br>laboratory test results (chemistry, hematology, and<br /><br>urinalysis). Adverse Events (AEs) and Serious Adverse Events (SAEs) are<br /><br>assessed through Day 5 and Day 14, respectively. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The secondary efficacy endpoints for RELAX-AHF are:<br /><br>1) Days alive out of hospital through Day 60<br /><br>2) Cardiovascular death or rehospitalization due to heart failure or renal<br /><br>failure through Day 60 </p><br>