Evaluation of the Effect of Injectable Neucardin on Cardiac Function and Reversal Ventricular Remodeling in Patients With Chronic Systolic Heart Failure
- Registration Number
- NCT05949801
- Lead Sponsor
- Zensun Sci. & Tech. Co., Ltd.
- Brief Summary
A multicenter, randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the effect of recombinant human Neuregulin-1 for injection on cardiac function and reverse ventricular remodeling in male patients with NT-proBNP ≤ 1700 pg/ml and female patients with NT-proBNP ≤ 4000 pg/ml and New York Heart Association class II-III chronic systolic heart failure, and to confirm its efficacy and safety.
- Detailed Description
This trial is planned to be conducted simultaneously in multiple clinical study sites nationwide, including 198 subjects, 99 subjects in the treatment group and 99 subjects in the placebo group.
Primary endpoint:
1.Response rate at 35 days of simultaneous reduction of LVESVI and LVEDVI by more than or equal to 20 ml/m2 (The proportion of the subjects achieving this criterion in each treatment group.)
Secondary endpoints:
1. Response rate at 35 day of LVESVI improvement greater than or equal to 25 ml/m2 ;
2. Response rate at 35 day of LVEDVI improvement greater than or equal to 25 ml/m2 ;
3. Change from baseline in LVEF, LVESV, LVEDV, LVESVI and LVEDVI at 35 days ;
4. 90-day response rate of LVESVI improved greater than or equal to 25ml/m2,LVEDVI improved greater than or equal to 25 ml/m2, and LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time ;
5. Change from baseline in LVEF, LVESV, LVEDV, LVESVI and LVEDVI at 90 days ;
6. Change from baseline in NYHA at 35 and 90 days ;
7. Change from baseline in quality of life at 35 and 90 days ;
8. Mortality during the study period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 202
- 18-75 years, male or female;
- Definite diagnosis of heart failure for 6 months or more, current stable disease, NYHA class II-III, left ventricular ejection fraction (LVEF) ≤ 40%(echocardiographic modified Simpson's method measurement ≤ 40% at screening, and CMR measurement ≤ 40% at baseline);
- NT-proBNP ≤1700 pg/ml in males and ≤4000pg/ml in females (detected by Roche kit in central laboratory);
- Receiving standard basic treatment for heart failure for at least 3 months, and did not change the type and dose of heart failure treatment drugs within 1 month;
- Understand and sign the informed consent form.
- Unable to receive CMR examination, such as patients with pacemakers, ICDs, CRTs, or other similar devices contraindicated for CMR, claustrophobia, atrial fibrillation during the screening period, or inability to cooperate with air-closed activities required for CMR testing;
- Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction, constrictive pericarditis, significant and uncorrected valvular heart disease, severe valvular regurgitation or severe stenosis, congenital heart disease requiring surgical treatment but not surgical treatment, primary pulmonary hypertension or secondary severe pulmonary hypertension (≥ 70 mmHg), and right heart failure due to pulmonary disease;
- Patients suffering from proliferative glands or adenomas with endocrine activity which may affect cardiac function or endocrine function, such as pheochromocytoma, thyromegaly, etc. (patients with euthyroid thyroid nodules do not need to be excluded);
- LVESVi less than 135 ml/m2 at baseline;
- Prepare to install pacemaker, ICD, CRT or other similar devices within 6 months;
- History of heart transplantation, use of ventricular assist devices (VADs) or preparation for heart transplantation, VADs;
- Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within the past 12 months;
- Subjects with chronic heart failure with acute hemodynamic disturbance or acute decompensation within the past 1 month (symptoms and signs prove that chronic heart failure is aggravated and intravenous drug therapy is required);
- Angina pectoris within the past 3 months;
- Myocardial infarction, cerebrovascular accident, revascularization (PCI or other surgery), cardiac surgery, carotid artery or other large vessel surgery within the past 6 months;
- Serious ventricular arrhythmias (sustained ventricular tachycardia or other conditions that the investigator considers necessary to exclude);
- Clinical diagnosis of pericardial effusion, pleural effusion or imaging showed pericardial effusion (greater than 50ml or 3 mm or a small amount or more) or pleural effusion (greater than 200ml or 10 mm);
- Liver and kidney dysfunction and chronic liver disease may have a potential impact on liver function (such as active chronic hepatitis, etc.), non-heart failure causes of bilirubin or alkaline phosphatase > 2 times the upper limit of normal, aspartate aminotransferase and/or alanine aminotransferase > 3 times the upper limit of normal, eGFR calculated using MDRD method < 30 ml/min/1.73 m2;
- Systolic blood pressure < 90 mmHg or > 160 mmHg;
- Serum K + < 3.2 mmol/L or > 5.5 mmol/L;
- Women of childbearing potential who plan to become pregnant within 2 years (women of childbearing potential are defined as all women with physical ability to become pregnant), pregnant or lactating women;
- Previous history of cancer or current cancer, or pathological examination confirmed precancerous lesions (Such as ductal carcinoma in situ of the breast, or atypical hyperplasia of the cervix), or through the examination (physical examination, X-ray examination or B ultrasound examination or other means) found in vivo malignant mass subjects;
- The investigator judges that the survival time is expected to be less than 6 months;
- Participated in any drug clinical trials within the first 3 months;
- Severe neurological disease (Alzheimer's disease, progressive parkinsonism);
- Subjects who are unable to complete this study or fail to comply with the requirements of this study (due to administrative reasons or other reasons), as judged by the investigator.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description placebo group Placebo Placebo + standard basic therapeutic medication Investigational drug group Neucardin Neucardin+standard basic therapeutic medication
- Primary Outcome Measures
Name Time Method Response rate at 35 days of simultaneous reduction of LVESVI and LVEDVI by more than or equal to 20 ml/m2 (The proportion of the subjects achieving this criterion in each treatment group) Day 35 Response rate at 35 days of simultaneous reduction of LVESVI and LVEDVI by more than or equal to 20 ml/m2 (The proportion of the subjects achieving this criterion in each treatment group)
- Secondary Outcome Measures
Name Time Method Change from baseline in LVESVI and LVEDVI at 90 days; Day 90 Change from baseline in LVESVI and LVEDVI at 90 days;
Change from baseline in New York Heart Association (NYHA) at 35 and 90 days; Day 35 and Day 90 Change from baseline in NYHA at 35 and 90 days;
Change from baseline in quality of life at 35 and 90 days; Day 35 and Day 90 Change from baseline in quality of life at 35 and 90 days;The benefit of patients is reflected by the quality of life score table.
Response rate at 35 day of left ventricular end systolic volume index (LVESVI) improvement greater than or equal to 25 ml/m2; Day 35 Response rate at 35 day of LVESVI improvement greater than or equal to 25 ml/m2;
Change from baseline in left ventricular ejection fraction (LVEF) at 35 days; Day 35 Change from baseline in LVEF at 35 days;
Mortality during the study period; Through study completion, an estimation of average of 1 year Mortality during the study period;
Change from baseline in LVEF at 90 days; Day 90 Change from baseline in LVEF at 90 days;
Change from baseline in LVESV at 90 days; Day 90 Change from baseline in LVESV at 90 days;
Response rate at 35 day of left ventricular end diastolic volume index (LVEDVI) improvement greater than or equal to 25 ml/m2; Day 35 Response rate at 35 day of LVEDVI improvement greater than or equal to 25 ml/m2;
Change from baseline in LVESVI and LVEDVI at 35 days; Day 35 Change from baseline in LVESVI and LVEDVI at 35 days;
Change from baseline in left ventricular end systolic volume (LVESV) at 35 days; Day 35 Change from baseline in LVESV at 35 days;
Change from baseline in left ventricular end diastolic volume (LVEDV) at 35 days; Day 35 Change from baseline in LVEDV at 35 days;
90-day response rate of LVESVI improved greater than or equal to 25 ml/m2; Day 90 90-day response rate of LVESVI improved greater than or equal to 25 ml/m2;
90-day response rate of LVEDVI improved greater than or equal to 25 ml/m2; Day 90 90-day response rate of LVEDVI improved greater than or equal to 25 ml/m2;
90-day response rate of LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time; Day 90 90-day response rate of LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time;
Change from baseline in LVEDV at 90 days; Day 90 Change from baseline in LVEDV at 90 days;
Trial Locations
- Locations (103)
Daqing Oilfield General Hospital
🇨🇳Daqing, Heilongjiang, China
Jiaxing First Hospital
🇨🇳Jiaxing, Zhejiang, China
Anyang People's Hospital (Anyang Central Hospital)
🇨🇳Anyang, Henan, China
Huaihe Hospital of Henan University
🇨🇳Kaifeng, Henan, China
Sanmenxia Central Hospital
🇨🇳Sanmenxia, Henan, China
First People's Hospital of Shangqiu
🇨🇳Shangqiu, Henan, China
Chenzhou First People's Hospital
🇨🇳Chenzhou, Huanan, China
People's Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Wuhan Wuchang Hospital
🇨🇳Wuhan, Hubei, China
Yueyang Central Hospital
🇨🇳Yueyang, Hunan, China
Zhongda Hospital Southeast University
🇨🇳Nanjing, Jiansu, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiansu, China
The Suzhou Municipal Hospital
🇨🇳Suzhou, Jiansu, China
Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiansu, China
Xuzhou Central Hospital
🇨🇳Xuzhou, Jiansu, China
Subei people's hospital
🇨🇳Yangzhou, Jiansu, China
China-Japan Union Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Jilin University Second Hospital
🇨🇳Changchun, Jilin, China
Benxi Central Hospital
🇨🇳Benxi, Liaoning, China
Tai'an City Central Hospital
🇨🇳Tai'an, Shandong, China
Zibo Municipal Hospital
🇨🇳Zibo, Shandong, China
Affiliated Hospital of Jining Medical College
🇨🇳Jining, Shangdong, China
Jining first people's hospital
🇨🇳Jining, Shangdong, China
Zaozhuang municipal hospital
🇨🇳Zaozhuang, Shangdong, China
Putuo District Central Hospital of Shanghai
🇨🇳Shanghai, Shanghai, China
Haikou People's Hospital
🇨🇳Haikou, Hainan, China
Hainan Provincial People's Hospital
🇨🇳Haikou, Hainan, China
Affiliated Hospital of Hangzhou Normal University
🇨🇳Hanzhou, Zhejiang, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Beijing Chao-Yang Hospital , Capital Medical University
🇨🇳Beijing, Beijing, China
Beijing Anzhen Hospital , Capital Medical University
🇨🇳Beijing, Beijing, China
Beijing Friendship Hospital , Capital Medical University
🇨🇳Beijing, Beijing, China
Chinese people's liberation army general hospital No.6 medical center
🇨🇳Beijing, Beijing, China
Peking University First Hospital
🇨🇳Beijing, Beijing, China
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
The First Medical Center of General Hospital of Chinese People's Liberation Army
🇨🇳Beijing, Beijing, China
Fuwai Hospital Chinese Academy of Medical Sciences
🇨🇳Beijin, Beijing, China
Chongqing Emergency Medical Center (Chongqing Fourth People's Hospital)
🇨🇳Chongqing, Chongqing, China
Chongqing University Three Gorges Hospital
🇨🇳Chongqing, Chongqing, China
Longyan First Hospital
🇨🇳Longyan, Fujian, China
Xiamen Cardiovascular Hospital Xiamen University
🇨🇳Xiamen, Fujian, China
First Affiliated Hospital of Sun Yat-sen University
🇨🇳Guangzhou, Guangdong, China
Guangdong Jieyang People's Hospital
🇨🇳Jieyang, Guangdong, China
Maoming people's hospital
🇨🇳Maoming, Guangdong, China
Liuzhou worker's hospital
🇨🇳Liuzhou, Guangxi Zhuang Autonomous Region, China
People's Hospital of Guangxi Zhuang Autonomous Region
🇨🇳Nanning, Guangxi Zhuang Autonomous Region, China
Affiliated Hospital of Hebei University
🇨🇳Baoding, Hebei, China
The First Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
The First Affiliated Hospital of Harbin Medical University
🇨🇳Ha'erbin, Heilongjiang, China
Qiqihar first hospital
🇨🇳Qiqihar, Heilongjiang, China
First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Luoyang, Henan, China
Luoyang Central Hospital
🇨🇳Luoyang, Henan, China
Nanyang Central Hospital
🇨🇳Nanyang, Henan, China
Nanyang First People's Hospital
🇨🇳Nanyang, Henan, China
General Hospital of Puyang Oilfield
🇨🇳Puyang, Henan, China
The First Affiliated Hospital of Xinxiang Medical College
🇨🇳Xinxiang, Henan, China
Xinxiang central hospital
🇨🇳Xinxiang, Henan, China
First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Henan University
🇨🇳Zhengzhou, Henan, China
Zhumadian Central Hospital
🇨🇳Zhumadian, Henan, China
Zhongnan Hospital of Wuhan University
🇨🇳Wuhan, Hubei, China
Xiangyang Central Hospital
🇨🇳Xiangyang, Hubei, China
Xiangyang first people's hospital
🇨🇳Xiangyang, Hubei, China
People's Hospital of Hunan Provincial
🇨🇳Changsha, Hunan, China
South China University Affiliated South China Hospital
🇨🇳Hengyang, Hunan, China
The Second Affiliated Hospital of Nanhua University
🇨🇳Hengyang, Hunan, China
Jiangxi Provincial People's Hospital
🇨🇳Nanchang, Jiangxi, China
Changzhou No.2 People's Hospital
🇨🇳Changzhou, Jiansu, China
The First People's Hospital of Changzhou
🇨🇳Changzhou, Jiansu, China
Huai'an First People's Hospital
🇨🇳Huai'an, Jiansu, China
The Second Affiliated Hospital of Nanjing Medical University
🇨🇳Nanjing, Jiansu, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Ansteel Group Genral Hospital
🇨🇳Anshan, Liaoning, China
The First Affiliated Hospital of Dalian Medical University
🇨🇳Dalian, Liaoning, China
Zhongshan Hospital Affiliated to Dalian University
🇨🇳Dalian, Liaoning, China
Central Hospital Affiliated to Shenyang Medical College
🇨🇳Shenyang, Liaoning, China
Liaoning Provincial People's Hospital
🇨🇳Shenyang, Liaoning, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Nanyang Second People's Hospital
🇨🇳Henan, Nanyang, China
Heze Municipal Hospital
🇨🇳Heze, Shandong, China
Jinan Central Hospital
🇨🇳Jinan, Shandong, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Shandong Province Qianfoshan Hospital
🇨🇳Jinan, Shandong, China
Linyi People's Hospital
🇨🇳Linyi, Shandong, China
Shanghai Baoshan District Wusong Central Hospital
🇨🇳Shanghai, Shanghai, China
Shanxi Provincial Cardiovascular Hospital
🇨🇳Taiyuan, Shanxi, China
The First Hospital of Shanxi Medical University
🇨🇳Taiyuan, Shanxi, China
The First Affiliated Hospital of Xi 'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
Xi'an Gaoxin Hospital
🇨🇳Xi'an, Shanxi, China
Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine
🇨🇳Xianyang, Shanxi, China
Xianyang first people's hospital
🇨🇳Xianyang, Shanxi, China
Xianyang Hospital of Yan 'an University
🇨🇳Xianyang, Shanxi, China
The Fifth People's Hospital of Chengdu
🇨🇳Chengdu, Sichuan, China
Mianyang Central Hospital
🇨🇳Mianyang, Sichuan, China
The First Affiliated Hospital of Dali University
🇨🇳Dali, Yunnan, China
Fuwai Yunnan Cardiovascular Hospital
🇨🇳Kunming, Yunnan, China
The First People's Hospital of Yunnan Province
🇨🇳Kunming, Yunnan, China
The First Affiliated Hospital , Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Sir Run Run Shaw Hospital
🇨🇳Hanzhou, Zhejiang, China
Ningbo Huamei Hospital, University of Chinese Academy of Sciences (Ningbo Second Hospital)
🇨🇳Ningbo, Zhejiang, China
The First Hospital of Ningbo
🇨🇳Ningbo, Zhejiang, China
First affiliated hospital of Wenzhou medical university
🇨🇳Wenzhou, Zhejiang, China