Survival Study of the Recombinant Human Neuregulin-1β in Subjects With Chronic Heart Failure.

A Multi-center, Randomized, Double-blined, Placebo Parallel Controlled Phase III Clinical Trial to Evaluate the Effect of Injectable Neucardin on the Mortality of Subjects With Chronic Systolic Heart Failure on Standard HF Therapy.

The purpose of this study is to evaluate efficacy of rhNRG-1 in reducing the death rate of heart failure subjects with baseline NT-proBNP level between 600 pg/ml and 1700 pg/mL and NYHA class II to III.

Study Overview

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

Detailed Description

The mortality of chronic heart failure patients remains high, in spite of current treatment. RhNRG-1(recombinant human neuregulin-1)directly work on the cardiomyocyte and restored the normal structure and function of it. Both the preclinical trials, phase II clinical trials and already completed phase III clinical trails have confirmed that rhNRG-1 effectively enhance the heart function, reverse the remodeling of left ventricular, and reduce all-cause mortality in heart failure animals and humans. More importantly, rhNRG-1 can significantly reduce the mortality of heart failure subjects with baseline NT-proBNP level ≤1600 fmol/mL and NYHA class II to III. In this phase III study, the investigators will further confirm the efficacy of rhNRG-1 in reducing the death rate of heart failure subjects with baseline NT-proBNP level between 600 pg/ml and 1700 pg/mL and NYHA class II to III.

• Study Type: Interventional
• Enrollment (Estimated): 1600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiaorui Wang, Ph.D; Phone Number: 196 86-21-50802627; Email: wangxiaorui@zensun.com
• Study Contact Backup: Name: Runlin Gao, Ph.D,MD

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100048
      • Recruiting
      • Navy General Hospital
      • Contact: Tianchang Li
      • Principal Investigator: Tianchang Li
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Beijing Hospital of Traditional Chinese Medicine
      • Contact: Hongxu Liu
      • Principal Investigator: Hongxu Liu
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Jingmei Group General Hospital
      • Contact: Jianping Luo
      • Principal Investigator: Jianping Luo
    • Beijing, Beijing, China
      • Recruiting
      • Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences
      • Contact: Jian Zhang, MD, Ph.D; Phone Number: 86-10-88398772
      • Principal Investigator: Jian Zhang, MD, Ph.D
  • Chongqing
    • Chongqing, Chongqing, China, 404000
      • Recruiting
      • Affiliated Hospital of Chongqing Three Gorges Medical College
      • Contact: Gang Xiong
      • Principal Investigator: Gang Xiong
    • Chongqing, Chongqing, China
      • Recruiting
      • Chongqing Emergency Medical Center
      • Contact: Ying Zhang
    • Chongqing, Chongqing, China
      • Recruiting
      • Chongqing Three Gorges Central Hospital
      • Contact: Xiaohua Pang
      • Principal Investigator: Xiaohua Pang
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Sun Yai-sen Memorial hospital Sun Yai-sen University
      • Contact: Jingfeng Wang
      • Principal Investigator: Jingfeng Wang
    • Guangzhou, Guangdong, China, 510317
      • Recruiting
      • Guangdong Second Provincial Central Hospital
      • Contact: Yuhui Li
      • Principal Investigator: Yuhui Li
    • Guangzhou, Guangdong, China, 511400
      • Recruiting
      • Guangzhou Panyu Central Hospital
      • Contact: Guoqin Chen
      • Principal Investigator: Guoqin Chen
    • Zhanjiang, Guangdong, China, 524001
      • Not yet recruiting
      • Affiliated Hospital of Guangdong Medical University
      • Contact: Jianying Chen
      • Principal Investigator: Jianying Chen
    • Zhuhai, Guangdong, China
      • Recruiting
      • The Fifth Affiliated Hospital Sun Yat-Sen University
      • Contact: Xiufang Lin
  • Guizhou
    • Zunyi, Guizhou, China, 133012
      • Recruiting
      • The First People's Hospital of Zunyi
      • Contact: Qianfeng Jiang
      • Principal Investigator: Qianfeng Jiang
  • Hainan
    • Haikou, Hainan, China
      • Recruiting
      • Haikou People's Hospital
      • Contact: Shijuan Lu
      • Principal Investigator: Shijuan Lu
    • Sanya, Hainan, China
      • Recruiting
      • The Third People's Hospital of Hainan Province
      • Contact: Ling Lin
      • Principal Investigator: Ling Lin
  • Hebei
    • Handan, Hebei, China, 056001
      • Recruiting
      • HanDan Central Hospital
      • Contact: Hongsen Tian
      • Principal Investigator: Hongsen Tian
    • Handan, Hebei, China, 056002
      • Recruiting
      • First Hospital of Handan
      • Contact: Xiufeng Zhao
      • Principal Investigator: Xiufeng Zhao
    • Shijiazhuang, Hebei, China, 05000
      • Recruiting
      • 980 Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital)
      • Contact: Ru Leisheng
      • Principal Investigator: Ru Leisheng
    • Xingtai, Hebei, China, 054000
      • Recruiting
      • The Second Affiliated Hospital of Xingtai Medical College
      • Contact: Dongmei Gao
      • Principal Investigator: Dongmei Gao
    • Xingtai, Hebei, China, 054000
      • Recruiting
      • Xingtai People's Hospital
      • Contact: Qingmin Wei
      • Principal Investigator: Qingmin Wei
  • Heilongjiang
    • Qiqihar, Heilongjiang, China, 161002
      • Recruiting
      • The Third Affiliated Hospital of Qiqihar Medical University
      • Contact: Haifeng Shao
      • Principal Investigator: Haifeng Shao
  • Henan
    • Kaifeng, Henan, China, 475000
      • Recruiting
      • Huaihe Hospital of Henan University
      • Contact: Ruili He
      • Principal Investigator: Ruili He
    • Luoyang, Henan, China
      • Recruiting
      • The First People's Hospital of Luoyang
      • Contact: Qunsheng Zhang
      • Principal Investigator: Qunsheng Zhang
    • Puyang, Henan, China, 457001
      • Recruiting
      • Puyang Oilfield General Hospital
      • Contact: Fuxian Ren
      • Principal Investigator: Fuxian Ren
      • Sub-Investigator: Yu Zhao
    • Xinxiang, Henan, China
      • Recruiting
      • The First People's Hospital of Xinxiang
      • Contact: Guiye Zhao
      • Principal Investigator: Guiye Zhao
    • Xinzheng, Henan, China, 451150
      • Recruiting
      • Pepole's Hospital of Xinzheng
      • Contact: Yanhong Li
      • Principal Investigator: Yanhong Li
    • Zhengzhou, Henan, China, 450004
      • Recruiting
      • Zhengzhou First People's Hospital
      • Contact: Hongwei Yu
      • Principal Investigator: Hongwei Yu
    • Zhengzhou, Henan, China, 471099
      • Recruiting
      • Luoyang center hospital
      • Contact: Shouyan Zhang
      • Principal Investigator: Shouyan Zhang
    • Zhengzhou, Henan, China
      • Recruiting
      • Henan Provincial Chest Hospital
      • Contact: Juan Chen
      • Principal Investigator: Juan Chen
  • Hunan
    • Changsha, Hunan, China, 410008
      • Recruiting
      • Xiangya Hospital Central South University
      • Contact: Zaixin Yu
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Provincial People's Hospital
      • Contact: Jianqiang Peng
      • Principal Investigator: Jianqiang Peng
    • Hengyang, Hunan, China, 421001
      • Recruiting
      • The Second Hospital. University of South China
      • Contact: Gaofeng Zeng
      • Principal Investigator: Gaofeng Zeng
  • Inner Mongolia
    • Baotou, Inner Mongolia, China
      • Recruiting
      • The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science & Technology
      • Principal Investigator: Xuefeng Lin
      • Contact: Xuefeng Lin
    • Chifeng, Inner Mongolia, China, 024000
      • Recruiting
      • Chifeng Municipal Hospital
      • Contact: Xiandong Sun
      • Principal Investigator: Xiandong Sun
  • Jiangsu
    • Xuzhou, Jiangsu, China
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical College
      • Contact: Yong Xia
      • Principal Investigator: Yong Xia, MD,Ph.D
  • Jiangxi
    • Jiujiang, Jiangxi, China, 332000
      • Recruiting
      • Jiujiang Hospital Affiliated to Nanchang University
      • Contact: Xihu Yin
      • Principal Investigator: Xihu Yin
  • Jilin
    • Chang Chun, Jilin, China, 130021
      • Recruiting
      • Jilin Academy of Traditional Chinese Medicine
      • Contact: Shurong Liu
      • Principal Investigator: Shurong Liu
    • Changchun, Jilin, China, 130021
      • Recruiting
      • Affiliated Hospital of Changchun University of Chinese Medicine
      • Contact: Yue Deng
      • Principal Investigator: Yue Deng
    • Changchun, Jilin, China
      • Recruiting
      • Jilin University Sino-Japanese Friendship Hospital
      • Contact: Fanbo Meng
      • Principal Investigator: Fanbo Meng
    • Changchun, Jilin, China
      • Recruiting
      • The First Affiliated Hospital of Jilin University
      • Contact: Yushi Wang
      • Principal Investigator: Yushi Wang
    • Meihekou, Jilin, China, 135000
      • Recruiting
      • Meihekou Central Hospital
      • Contact: Jinliang Zhang
      • Principal Investigator: Jinliang Zhang
    • Siping, Jilin, China
      • Recruiting
      • Siping Central People's Hospital
      • Contact: Zhihua Fang
      • Principal Investigator: Zhihua Fang
    • Tonghua, Jilin, China, 134000
      • Recruiting
      • Tonghua Central Hospital
      • Contact: Xuxia Zhang
      • Principal Investigator: Xuxia Zhang
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • Shengjing Hospital affiliated to China Medical University
      • Contact: Shumei Ma
      • Principal Investigator: Shumei Ma
    • Shenyang, Liaoning, China, 110016
      • Recruiting
      • The People's Hospital of Liaoning Province
      • Contact: Zhanquan Li
      • Principal Investigator: Zhanquan Li
  • Shaanxi
    • Xianyang, Shaanxi, China, 712000
      • Recruiting
      • The Affiliated Hospital of Shaanxi University of Chinese Medicine
      • Contact: Ling Chen
      • Principal Investigator: Ling Chen
  • Shandong
    • Jinan, Shandong, China, 250013
      • Recruiting
      • Jinan Central Hospital
      • Contact: Wei Miao
      • Principal Investigator: Wei Miao
    • Jinan, Shandong, China
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Ming Zhong, MD,Ph.D
      • Principal Investigator: Ming Zhong, MD,Ph.D
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Oriental Hospital
      • Contact: Huimin Fan
      • Principal Investigator: Huimin Fan
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Central Hospital of Minhang District
      • Principal Investigator: Wei Hu
      • Contact: Wei Hu
    • Shanghai, Shanghai, China, shanghai
      • Recruiting
      • The Sixth People's Hospital, Shanghai Jiaotong University
      • Contact: Jingwei Pan
      • Principal Investigator: Jingwei Pan
    • Shanghai, Shanghai, China
      • Recruiting
      • Shanghai Yangpu District Central Hospital
      • Contact: Jiahong Wang
      • Principal Investigator: Jiahong Wang
    • Shanghai, Shanghai, China
      • Recruiting
      • The Central Hospital of Putuo District, Shanghai
      • Contact: Zongjun Liu, MD,Ph.D
      • Principal Investigator: Zongjun Liu, MD,Ph.D
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • Recruiting
      • Second Hospital of Shanxi Medical University
      • Contact: Zhiming Yang
      • Principal Investigator: Zhiming Yang
    • Taiyuan, Shanxi, China, 030024
      • Recruiting
      • Shanxi cardiovascular disease hospital
      • Contact: Huiyuan Han
      • Principal Investigator: Huiyuan Han
    • Taiyuan, Shanxi, China
      • Suspended
      • Taiyuan City Central Hospital
  • Sichuan
    • Deyang, Sichuan, China, 618000
      • Recruiting
      • Pepole's hospital of DeYang city
      • Contact: Xiaojian Deng
      • Principal Investigator: Xiaojian Deng
    • Neijiang, Sichuan, China
      • Recruiting
      • The Second People's Hospital of Neijiang
      • Contact: Quanwei Liu
      • Principal Investigator: Quanwei Liu
  • Tianjing
    • Tianjing, Tianjing, China, 300000
      • Recruiting
      • Wuqing pepole's hospital
      • Contact: Feng Ling
      • Principal Investigator: Feng Ling
  • Xinjiang
    • Xinjiang, Xinjiang, China, 830054
      • Recruiting
      • Fourth Affiliated Hospital of Xinjiang Medical University
      • Contact: Peng Li
      • Principal Investigator: Peng Li
  • Yunnan
    • Kunming, Yunnan, China, 650011
      • Recruiting
      • The Third People's Hospital of Yunnan Province
      • Contact: Yunfei Hong
    • Kunming, Yunnan, China
      • Recruiting
      • The Second Hospital of Kunming Medical College
      • Contact: Wenwei Bai
      • Principal Investigator: Wenwei Bai
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • Shulan (Hangzhou) hospital
      • Contact: Liping Ma
      • Principal Investigator: Liping Ma
    • Linhai, Zhejiang, China
      • Recruiting
      • Taizhou Hospital of Zhejiang Province
      • Contact: Jianjun Jiang
      • Principal Investigator: Jianjun Jiang
    • Quzhou, Zhejiang, China
      • Recruiting
      • Quzhou People's Hospital
      • Contact: Xiaoming Tu
      • Principal Investigator: Xiaoming Tu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Age between 18 and 75, gender balance (no more than 960 subjects of either gender in total 1600 subjects).
• 2. Left ventricular ejection fraction (LVEF)≤40% (ECHO).
• 3. Subjects with chronic heart failure (NYHA class II OR III ).
• 4. 600 pg/ml ≤NT-proBNP≤1700 pg/ml ( by Roche assay Kit in central lab).
• 5. Diagnosed as chronic systolic heart failure (history, symptoms, signs), and in stable condition in the last one month.
• 6. Receiving standard therapy for chronic heart failure, reach target dose or max tolerable dose for one month, or has not changed the dose for one month before randomization.
• 7. Capable of signing the informed consent form.

Exclusion Criteria:

• 1. New chronic heart failure patients, or patients receiving standard therapy on chronic heart failure for less than 3 months.
• 2. NYHA functional class I OR IV.
• 3. NT-proBNP < 600 pg/ml OR NT-proBNP>1700 pg/ml (by Roche assay Kit in central lab).
• 4. Patients with hypertrophic cardiomyopathy, rheumatic heart disease, constrictive pericarditis, significant valvular pathological change or congenital heart diseases, primary or secondary severe pulmonary artery hypertension.
• 5. Ischemic heart failure without recanalization or with recanalization in recent six months.
• 6. Acute MI in the last 3 months.
• 7. Unstable angina.
• 8. Patients with acute pulmonary edema or acute hemodynamic disorder.
• 9. Chronic heart failure patients with acute hemodynamic disorder or acute decompensation in the last 1 month (symptoms and signs suggest worsening chronic heart failure and may require intravenous drug therapy).
• 10. Patients with right heart failure caused by pulmonary disease.
• 11. Patients diagnosed with pericardial effusion (>50 ml) or pleural effusion(>200 ml), or evidenced by Echocardiogram.
• 12. Cardiac surgery or cerebrovascular accident within recent six months.
• 13. Preparing for heart transplantation or CRT, or has received CRT.
• 14. Serious ventricular arrhythmia (sustained ventricular tachycardia or frequent paroxysmal ventricular tachycardia).
• 15.Diagnosis of perinatal or chemotherapy-induced cardiomyopathy in last 12 months.
• 16. Serious hepatic or renal dysfunction (bilirubin 1.5 times above the normal upper limit, AST or ALT 2 times above the normal upper limit, serum creatinine>2.0mg/dL, HBV or HCV positive).
• 17. Serum potassium <3.2 mmol/L or >5.5 mmol/L.
• 18. Systolic blood pressure <90mmHg or >160mmHg.
• 19. Women of childbearing age who have a pregnancy plan within 2 years (women of childbearing age are defined as women who have a pregnancy physiology).
• 20. Pregnant or lactating women.
• 21. Patients who participated in any clinical trial in the recent three months.
• 22. Subject with a life expectancy less than 6 months as assessed by the investigator.
• 23. Serious nervous system diseases (Alzheimer's disease, advanced Parkinsonism),lower limb defects, or deaf-mute.
• 24. History of any malignancy or suffering from cancer, or biopsy proven pre-malignant condition (e.g., DICS or cervical atypia).
• 25. Evidence (physical examination, chest X-ray (CXR), ECHO or other tests) shows some active malignancy or adenoidal hypertrophy or neoplasm that has an effect on heart function or the endocrine system, e.g., pheochromocytoma or hyperthyroidism (Thyroid nodules with normal thyroid function do not need to be excluded).
• 26. As judged by the investigator that the subject cannot 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
Placebo Comparator: Placebo; Placebo in addition to standard therapy	Drug: Placebo; 10 hours per day i.v drip for the first 10 days (0ug/kg/day), followed by weekly 10 minutes i.v bolus (0ug/kg/day), from the 3rd week for 23 weeks
Experimental: rhNRG-1; rhNRG-1 in addition to standard therapy	Drug: rhNRG-1; 10 hours per day i.v drip for the first 10 days (0.6ug/kg/day), followed by weekly 10 minutes i.v bolus (0.8ug/kg/day), from the 3rd week for 23 weeks; Other Names: Neucardin™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause mortality	Including deaths from cardiovascular and non-cardiovascular causes, Log-Rank test was used for comparison between groups, and Kaplan-Meier survival curves were plotted; COX proportional hazard model was used to estimate the HR and its 95% confidence interval.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality caused by cardiovascular events	Log-Rank test was used for comparison between groups, and Kaplan-Meier survival curves were plotted; COX proportional hazard model was used to estimate the HR and its 95% confidence interval.	1 year
All-cause mortality of female subjects	Log-Rank test was used for comparison between groups, and Kaplan-Meier survival curves were plotted; COX proportional hazard model was used to estimate the HR and its 95% confidence interval.	1 year
All-cause mortality of male subjects	Log-Rank test was used for comparison between groups, and Kaplan-Meier survival curves were plotted; COX proportional hazard model was used to estimate the HR and its 95% confidence interval.	1 year
Percentage of all-cause re-hospitalization	The Kaplan-Meier curve was used to describe the cumulative incidence rate of the first re-hospitalization, and the differences between the two groups were compared using Log-Rank.	1 year
Percentage of Participants with re-hospitalization caused by worsening heart failure	The Kaplan-Meier curve was used to describe the cumulative incidence rate of the first re-hospitalization, and the differences between the two groups were compared using Log-Rank.	1 year
Change of NT-proBNP level at the 25th week and 52th week	The paired t test or signed rank sum test was used to compare the changes before and after treatment in each group, and the comparison between groups was performed by analysis of variance or Wilcoxon rank sum test.	1 year
New York Heart Association (NYHA) functional classification	For the NYHA cardiac functional grading after administration, summarize the number and percentage of subjects by different study visit period, compare the efficacy differences among test groups and control groups. In addition, calculate the changes of NYHA cardiac functional grade from baseline of the subjects. The intragroup changes will be analyzed by signed-rank sum test, intergroup comparison will be conducted by Wilcoxon test.	1 year

Collaborators and Investigators

• Sponsor: Zensun Sci. & Tech. Co., Ltd.
• Investigators: Principal Investigator: Runlin Gao, Ph.D,MD, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2018
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: December 19, 2017
• First Submitted That Met QC Criteria: December 24, 2017
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: mortality; chronic heart failure; neuregulin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: ZS-01-306

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No