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

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

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Systolic Heart Failure
• Intervention / Treatment: Drug: rhNRG-1; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Anzhen Hospital, Affiliate of Capital University of Medical Sciences
    • Beijing, Beijing, China
      • Beijing Chao Yang Hospital, Affiliate of Capital University of Medical Sciences
    • Beijing, Beijing, China
      • Cardiovascular Institute and Fuwai Hospital
    • Beijing, Beijing, China
      • General Hospital of Chinese People's Liberation Army

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age between 18 and 75, both sex.
2. Left ventricular ejection fraction (LVEF)≤40% (ECHO).
3. NYNA functional class II~III.
4. Definitely diagnosed with chronic systolic heart failure (including medical records, symptoms and physical signs)and clinical symptom is steadily in the latest 1 month.
5. 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.
6. Capable of signing the informed consent form.

Exclusion Criteria:

1. Patients with atrial fibrillation.
2. Patients with a pacemaker.
3. Patient with a metallic implant.
4. Patient with Claustrophobia.
5. Patients with acute myocardial infarction, Hypertrophic cardiomyopathy, constrictive pericarditis, significant valvular pathological change or congenital heart diseases, severe pulmonary artery hypertension.
6. Ischemic heart failure without recanalization or with recanalization in recent six months.
7. Cardiac surgery or cerebrovascular accident within recent six months.
8. Preparing for heart transplantation or has received CRT treatment.
9. Serious hepatic or renal dysfunction caused by organic pathological changes (Cr>2.0mg/dl, AST or ALT 5 times above the normal upper limit).
10. Patients need mechanical ventilation.
11. Systolic blood pressure <90mmHg or >160mmHg.
12. Patients with acute hemodynamic disorder or decompensation in the last 1 month.
13. Serious ventricular arrhythmia (multi-morphological premature ventricular contraction, frequent paroxysmal ventricular tachycardia).
14. Serum potassium <3.2 mmol/L or >5.5 mmol/L.
15. Pregnant or plan to pregnant.
16. Unmarried or married but not procreated women at child-bearing age.
17. Subject with a life expectancy less than 6 months as assessed by the investigator.
18. Patients who participated in any clinical trial in the recent three months.
19. History of any malignancy or suffering from cancer,or biopsy proven pre-malignant condition (eg DICS or cervical atypia).
20. 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.
21. Judging by the investigator, the patients could not complete the study or adhere to the study requirements (due to the management reasons or others).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Left Ventricular Ejection Fraction	30 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Zensun Sci. & Tech. Co., Ltd.

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: September 21, 2011
• First Submitted That Met QC Criteria: September 22, 2011
• First Posted (Estimate): September 23, 2011

Study Record Updates

• Last Update Posted (Actual): December 21, 2017
• Last Update Submitted That Met QC Criteria: December 19, 2017
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Chronic heart failure; rhNRG-1; Cardiac remodeling
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Murmurs; Heart Failure; Systolic Murmurs; Heart Failure, Systolic
• Other Study ID Numbers: ZS-01-303