Clinical trial NCT03388593: Survival Study of the Recombinant Human Neuregulin-1β in Subjects With Chronic Heart Failure.
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Heart Failure
Keywords: chronic heart failure
neuregulin
mortality
Lead sponsor: Zensun Sci. & Tech. Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-01-03
Enrollment: 1600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: All-cause mortality
timeFrame: 1 year
Secondary outcomes:
measure: Mortality caused by cardiovascular events
timeFrame: 1 year
measure: All-cause mortality of female subjects
timeFrame: 1 year
measure: All-cause mortality of male subjects
timeFrame: 1 year
measure: Percentage of all-cause re-hospitalization
timeFrame: 1 year
measure: Percentage of Participants with re-hospitalization caused by worsening heart failure
timeFrame: 1 year
measure: Change of NT-proBNP level at the 25th week and 52th week
timeFrame: 1 year
measure: New York Heart Association (NYHA) functional classification
timeFrame: 1 year
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Hospital of Traditional Chinese Medicine
state: Beijing
city: Beijing
country: China
facility: Navy General Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Jingmei Group General Hospital
state: Beijing
city: Beijing
country: China
facility: Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences
state: Beijing
city: Chongqing
country: China
facility: Affiliated Hospital of Chongqing Three Gorges Medical College
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Emergency Medical Center
state: Chongqing
city: Chongqing
country: China
facility: Chongqing Three Gorges Central Hospital
state: Chongqing
city: Guangzhou
country: China
facility: Sun Yai-sen Memorial hospital Sun Yai-sen University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Second Provincial Central Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Guangzhou Panyu Central Hospital
state: Guangdong
city: Zhanjiang
country: China
facility: Affiliated Hospital of Guangdong Medical University
state: Guangdong
city: Zhuhai
country: China
facility: The Fifth Affiliated Hospital Sun Yat-Sen University
state: Guangdong
city: Zunyi
country: China
facility: The First People's Hospital of Zunyi
state: Guizhou
city: Haikou
country: China
facility: Haikou People's Hospital
state: Hainan
city: Sanya
country: China
facility: The Third People's Hospital of Hainan Province
state: Hainan
city: Handan
country: China
facility: HanDan Central Hospital
state: Hebei
city: Handan
country: China
facility: First Hospital of Handan
state: Hebei
city: Shijiazhuang
country: China
facility: 980 Hospital of PLA Joint Logistics Support Force (Bethune International Peace Hospital)
state: Hebei
city: Xingtai
country: China
facility: The Second Affiliated Hospital of Xingtai Medical College
state: Hebei
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Qiqihar
country: China
facility: The Third Affiliated Hospital of Qiqihar Medical University
state: Heilongjiang
city: Kaifeng
country: China
facility: Huaihe Hospital of Henan University
state: Henan
city: Luoyang
country: China
facility: The First People's Hospital of Luoyang
state: Henan
city: Puyang
country: China
facility: Puyang Oilfield General Hospital
state: Henan
city: Xinxiang
country: China
facility: The First People's Hospital of Xinxiang
state: Henan
city: Xinzheng
country: China
facility: Pepole's hospital of Xinzheng
state: Henan
city: Zhengzhou
country: China
facility: Zhengzhou First People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Luoyang center hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial Chest Hospital
state: Henan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Hengyang
country: China
facility: The Second Hospital. University of South China
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science & Technology
state: Inner Mongolia
city: Chifeng
country: China
facility: Chifeng Municipal Hospital
state: Inner Mongolia
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College
state: Jiangsu
city: Jiujiang
country: China
facility: Jiujiang Hospital Affiliated to Nanchang University
state: Jiangxi
city: Chang Chun
country: China
facility: Jilin Academy of Traditional Chinese Medicine
state: Jilin
city: Changchun
country: China
facility: Affiliated Hospital of Changchun University of Chinese Medicine
state: Jilin
city: Changchun
country: China
facility: Jilin University Sino-Japanese Friendship Hospital
state: Jilin
city: Changchun
country: China
facility: The First Affiliated Hospital of Jilin University
state: Jilin
city: Meihekou
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Siping
country: China
facility: Siping Central People's Hospital
state: Jilin
city: Tonghua
country: China
facility: Tonghua Central Hospital
state: Jilin
city: Shenyang
country: China
facility: The People's Hospital of Liaoning Province
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital Affiliated to China Medical University
state: Liaoning
city: Xianyang
country: China
facility: The Affiliated Hospital of Shaanxi University of Chinese Medicine
state: Shaanxi
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Central hospital of minhang District
state: Shanghai
city: Shanghai
country: China
facility: The Sixth People's Hospital, Shanghai Jiaotong University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Oriental hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Yangpu District Central Hospital
state: Shanghai
city: Shanghai
country: China
facility: The Central Hospital of Putuo District, Shanghai
state: Shanghai
city: Taiyuan
country: China
facility: Second Hospital of Shanxi Medical University
state: Shanxi
city: Taiyuan
country: China
facility: Shanxi cardiovascular disease hospital
state: Shanxi
city: Taiyuan
country: China
facility: Taiyuan City Central Hospital
state: Shanxi
city: Deyang
country: China
facility: Pepole's hospital of DeYang city
state: Sichuan
city: Neijiang
country: China
facility: The Second People's Hospital of Neijiang
state: Sichuan
city: Tianjing
country: China
facility: Wuqing pepole's hospital
state: Tianjing
city: Xinjiang
country: China
facility: Fourth Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: The Third People's Hospital of Yunnan Province
state: Yunnan
city: Kunming
country: China
facility: The Second Hospital of Kunming Medical College
state: Yunnan
city: Hangzhou
country: China
facility: Shulan (Hangzhou) Hospital
state: Zhejiang
city: Linhai
country: China
facility: Taizhou Hospital of Zhejiang Province
state: Zhejiang
city: Quzhou
country: China
facility: Quzhou people's hospital
state: Zhejiang
Study officials:
affiliation: Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences
name: Runlin Gao, Ph.D,MD
role: PRINCIPAL_INVESTIGATOR
References: