Study of Efficacy on Cardiac Remodeling of Recombinant Human Neuregulin-1 in Stable Chronic Systolic Heart Failure Patients

Study Overview
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Brief Summary
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This is a multi-center, randomized, double-blind , placebo parallel controlled, standard therapy based phase III clinical trial, to evaluate the efficacy of recombinant human neuregulin-1 on cardiac remodeling, as well as safety in patients with chronic heart failure.

Detailed Description
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RhNRG-1(recombinant human neuregulin-1)directly works on the cardiomyocytes and restored the normal structure and function of it.Both the preclinical trial and phase II clinical trail have confirmed that rhNRG-1 effectively improved the heart function, and is tolerated in the effective dosage groups. The aim of this phase III trial is to further confirm in large population that rhRNG-1 administration can effectively improve the cardiac remodeling and is tolerated in patients with chronic heart failure.

Official Title
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A Phase III, Multi-center,Randomized, Double-blind, Based on Standard Therapy, Placebo-controlled Study of the Efficacy/Safety of Recombinant Human Neuregulin-1β in Patients With Chronic Systolic Heart Failure

Conditions
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Chronic Systolic Heart Failure

Intervention / Treatment
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* Drug: rhNRG-1
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 75, both sex. Left ventricular ejection fraction (LVEF)≤40% (ECHO). NYNA functional class II III. Definitely diagnosed with chronic systolic heart failure (including medical records, symptoms and physical signs)and clinical symptom is steadily in the latest 1 month. Receiving standard basic treatment of heart failure, has reached the objective dosage or the highest tolerated dosage for at least 1 month, or the dosage has not been changed for at least 1 month. Capable of signing the informed consent form. Exclusion Criteria: Patients with atrial fibrillation. Patients with a pacemaker. Patient with a metallic implant. Patient with Claustrophobia. Patients with acute myocardial infarction, Hypertrophic cardiomyopathy, constrictive pericarditis, significant valvular pathological change or congenital heart diseases, severe pulmonary artery hypertension. Ischemic heart failure without recanalization or with recanalization in recent six months. Cardiac surgery or cerebrovascular accident within recent six months. Preparing for heart transplantation or has received CRT treatment. Serious hepatic or renal dysfunction caused by organic pathological changes (Cr>2.0mg/dl, AST or ALT 5 times above the normal upper limit). Patients need mechanical ventilation. Systolic blood pressure <90mmHg or >160mmHg. Patients with acute hemodynamic disorder or decompensation in the last 1 month. Serious ventricular arrhythmia (multi-morphological premature ventricular contraction, frequent paroxysmal ventricular tachycardia). Serum potassium <3.2 mmol/L or >5.5 mmol/L. Pregnant or plan to pregnant. Unmarried or married but not procreated women at child-bearing age. Subject with a life expectancy less than 6 months as assessed by the investigator. Patients who participated in any clinical trial in the recent three months. History of any malignancy or suffering from cancer,or biopsy proven pre-malignant condition (eg DICS or cervical atypia). Evidence (physical examination,CXR,ECHO or other tests) shows some active malignancy or adenoidal hypertrophy or neoplasm has effect on heart function or endocrine system, eg pheochromocytoma or hyperthyroidism. Judging by the investigator, the patients could not complete the study or adhere to the study requirements (due to the management reasons or others).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: rhNRG-1<br>Recombinant human neuregulin-1 administration in addition to basic therapy of chronic heart failure | Drug: rhNRG-1<br>* day1 day10:0.6ug/kg/day,10hours per day for vein infusion<br>|
| Placebo Comparator: Placebo<br>Excipient placebo in addition to basic therapy of chronic heart failure | Drug: Placebo<br>* day1 day10:0.6ug/kg/day,10hours per day for vein infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Ejection Fraction |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Ejection Fraction |  | 90 days | 
| N-terminal pro-BNP |  | 30 days and 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic heart failure, rhNRG-1, Cardiac remodeling