Study of Efficacy on NT-proBNP of Recombinant Human Neuregulin-1 in Chronic 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

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 serum NT-proBNP, as well as safety in patients with chronic heart failure.

Study Overview

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

Detailed Description

N-terminal proNBP (NT-proBNP) has been proved to be an independent prognostic factor for the long-term prognosis of chronic heart failure patients.RhNRG-1(recombinant human neuregulin-1)directly works on the cardiomyocytes and restored the normal structure and function of it. It has been found that rhNRG-1 effectively decreased the serum level of NT-proBNP,and is tolerated in the effective dosages groups.The aim of this phase III trial is to further confirm in large population that rhRNG-1 administration can effectively decrease the serum level of NT-proBNP and is tolerated in patients with chronic heart failure.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Cardiovascular Institute and Fuwai Hospital
  • Hebei
    • Shijiazhuang, Hebei, China
      • Bethune Peace Hospital
    • Tianjin, Hebei, China
      • TEDA International Cardiovascular Hospital
  • Heilongjiang
    • Daqing, Heilongjiang, China
      • Daqing Oilfield General Hospital
    • Haerbin, Heilongjiang, China
      • The First Hospital of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Hunan
    • Changsha, Hunan, China
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • Chengdu, Jiangsu, China
      • Sichuan Provincial People's Hospital
    • Suzhou, Jiangsu, China
      • The Second Hospital Affiliated To Suzhou University
    • Yangzhou, Jiangsu, China
      • North Jiangsu People's Hospital
    • Zhenjiang, Jiangsu, China
      • The Affiliate Hospital of Jiangsu University
  • Jilin
    • Changchun, Jilin, China
      • The Second Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China
      • The First Hospital affiliated to Dalian Medical University
    • Jinzhou, Liaoning, China
      • The first affiliated hospital of Liaoning medical college
    • Shenyang, Liaoning, China
      • Shengjing Hospital of China Medical University
    • Shenyang, Liaoning, China
      • Liaoning Provincial People's Hospital
  • Shandong
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai Sixth People's Hospital
    • Shanghai, Shanghai, China
      • Shanghai First People's Hospital
  • Sichuan
    • Chongqing, Sichuan, China
      • The Xinqiao Hospital of Third Military Medical University
  • Yunnan
    • Kunming, Yunnan, China
      • Kunming General Hospital of Chengdu Military Region

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 acute myocardial infarction, Hypertrophic cardiomyopathy, constrictive pericarditis, significant valvular pathological change or congenital heart diseases, severe pulmonary artery hypertension.
2. Ischemic heart failure without recanalization or with recanalization in recent six months.
3. Cardiac surgery or cerebrovascular accident within recent six months.
4. Preparing for heart transplantation or has received CRT treatment.
5. Serious hepatic or renal dysfunction caused by organic pathological changes (Cr>2.0mg/dl, AST or ALT 5 times above the normal upper limit).
6. Patients need mechanical ventilation.
7. Systolic blood pressure <90mmHg or >160mmHg.
8. Patients with acute hemodynamic disorder or decompensation in the last 1 month.
9. Serious ventricular arrhythmia (multi-morphological premature ventricular contraction, frequent paroxysmal ventricular tachycardia).
10. Serum potassium <3.2 mmol/L or >5.5 mmol/L.
11. Pregnant or plan to pregnant.
12. Unmarried or married but not procreated women at child-bearing age.
13. Subject with a life expectancy less than 6 months as assessed by the investigator.
14. Patients who participated in any clinical trial in the recent three months.
15. History of any malignancy or suffering from cancer,or biopsy proven pre-malignant condition (eg DICS or cervical atypia).
16. 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.
17. 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
• 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: Plaebo; 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
NT-proBNP	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
NT-proBNP	90 days
Six Minutes Walk Distance	30 days and 90 days
NYHA classification	30 days and 90 days
Quality of Life	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; NT-proBNP; rhNRG-1
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: ZS-01-304