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

Chronic Heart Failure Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03388593
• Other study ID #: ZS-01-306
• Status: Recruiting
• Phase: Phase 3
• Start date: July 23, 2018
• Est. completion date: February 2026

Study information

• Verified date: January 2024
• Source: Zensun Sci. & Tech. Co., Ltd.
• Contact: Xiaorui Wang, Ph.D
• Phone: 86-21-50802627
• Email: wangxiaorui[@]zensun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1600
• Est. completion date: February 2026
• Est. primary completion date: February 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

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
• 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

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science & Technology	Baotou	Inner Mongolia
China	Beijing Hospital of Traditional Chinese Medicine	Beijing	Beijing
China	Beijing Jingmei Group General Hospital	Beijing	Beijing
China	Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Navy General Hospital	Beijing	Beijing
China	Jilin Academy of Traditional Chinese Medicine	Chang Chun	Jilin
China	Affiliated Hospital of Changchun University of Chinese Medicine	Changchun	Jilin
China	Jilin University Sino-Japanese Friendship Hospital	Changchun	Jilin
China	The First Affiliated Hospital of Jilin University	Changchun	Jilin
China	Hunan Provincial People's Hospital	Changsha	Hunan
China	Xiangya Hospital Central South University	Changsha	Hunan
China	Chifeng Municipal Hospital	Chifeng	Inner Mongolia
China	Affiliated Hospital of Chongqing Three Gorges Medical College	Chongqing	Chongqing
China	Chongqing Emergency Medical Center	Chongqing	Chongqing
China	Chongqing Three Gorges Central Hospital	Chongqing	Chongqing
China	Pepole's hospital of DeYang city	Deyang	Sichuan
China	Guangdong Second Provincial Central Hospital	Guangzhou	Guangdong
China	Guangzhou Panyu Central Hospital	Guangzhou	Guangdong
China	Sun Yai-sen Memorial hospital Sun Yai-sen University	Guangzhou	Guangdong
China	Haikou People's Hospital	Haikou	Hainan
China	First Hospital of Handan	Handan	Hebei
China	HanDan Central Hospital	Handan	Hebei
China	Shulan (Hangzhou) Hospital	Hangzhou	Zhejiang
China	The Second Hospital. University of South China	Hengyang	Hunan
China	Jinan Central Hospital	Jinan	Shandong
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Jiujiang Hospital Affiliated to Nanchang University	Jiujiang	Jiangxi
China	Huaihe Hospital of Henan University	Kaifeng	Henan
China	The Second Hospital of Kunming Medical College	Kunming	Yunnan
China	The Third People's Hospital of Yunnan Province	Kunming	Yunnan
China	Taizhou Hospital of Zhejiang Province	Linhai	Zhejiang
China	The First People's Hospital of Luoyang	Luoyang	Henan
China	Meihekou Central Hospital	Meihekou	Jilin
China	The Second People's Hospital of Neijiang	Neijiang	Sichuan
China	Puyang Oilfield General Hospital	Puyang	Henan
China	The Third Affiliated Hospital of Qiqihar Medical University	Qiqihar	Heilongjiang
China	Quzhou people's hospital	Quzhou	Zhejiang
China	The Third People's Hospital of Hainan Province	Sanya	Hainan
China	Central hospital of minhang District	Shanghai	Shanghai
China	Shanghai Oriental hospital	Shanghai	Shanghai
China	Shanghai Yangpu District Central Hospital	Shanghai	Shanghai
China	The Central Hospital of Putuo District, Shanghai	Shanghai	Shanghai
China	The Sixth People's Hospital, Shanghai Jiaotong University	Shanghai	Shanghai
China	Shengjing Hospital Affiliated to China Medical University	Shenyang	Liaoning
China	The People's Hospital of Liaoning Province	Shenyang	Liaoning
China	980 Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital)	Shijiazhuang	Hebei
China	Siping Central People's Hospital	Siping	Jilin
China	Second Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Shanxi cardiovascular disease hospital	Taiyuan	Shanxi
China	Taiyuan City Central Hospital	Taiyuan	Shanxi
China	Wuqing pepole's hospital	Tianjing	Tianjing
China	Tonghua Central Hospital	Tonghua	Jilin
China	The Affiliated Hospital of Shaanxi University of Chinese Medicine	Xianyang	Shaanxi
China	The Second Affiliated Hospital of Xingtai Medical College	Xingtai	Hebei
China	Xingtai People's Hospital	Xingtai	Hebei
China	Fourth Affiliated Hospital of Xinjiang Medical University	Xinjiang	Xinjiang
China	The First People's Hospital of Xinxiang	Xinxiang	Henan
China	Pepole's hospital of Xinzheng	Xinzheng	Henan
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Jiangsu
China	Affiliated Hospital of Guangdong Medical University	Zhanjiang	Guangdong
China	Henan Provincial Chest Hospital	Zhengzhou	Henan
China	Luoyang center hospital	Zhengzhou	Henan
China	Zhengzhou First People's Hospital	Zhengzhou	Henan
China	The Fifth Affiliated Hospital Sun Yat-Sen University	Zhuhai	Guangdong
China	The First People's Hospital of Zunyi	Zunyi	Guizhou

Sponsors (1)

Lead Sponsor	Collaborator
Zensun Sci. & Tech. Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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