Evaluation of the Effect of Injectable Neucardin on Cardiac Function and Reversal Ventricular Remodeling in Patients With Chronic Systolic Heart Failure

Chronic Systolic Heart Failure Clinical Trial

Official title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial Based on Standard Treatment to Evaluate the Effect of Injectable Neucardin on Cardiac Function and Reverse Ventricular Remodeling in Patients With Chronic Systolic Heart Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05949801
• Other study ID #: ZS-01-308B
• Status: Recruiting
• Phase: Phase 3
• Start date: April 13, 2023
• Est. completion date: August 2024

Study information

• Verified date: July 2023
• Source: Zensun Sci. & Tech. Co., Ltd.
• Contact: Xiaoyan Qin, ph.D
• Phone: 86-021-50802627
• Email: qinxiaoyan[@]zensun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 198
• Est. completion date: August 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. 18-75 years, male or female;

2. 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);

3. NT-proBNP =1700 pg/ml in males and =4000pg/ml in females (detected by Roche kit in central laboratory);

4. 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;

5. Understand and sign the informed consent form.

Exclusion Criteria:

1. 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;

2. 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;

3. 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);

4. LVESVi less than 135 ml/m2 at baseline;

5. Prepare to install pacemaker, ICD, CRT or other similar devices within 6 months;

6. History of heart transplantation, use of ventricular assist devices (VADs) or preparation for heart transplantation, VADs;

7. Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within the past 12 months;

8. 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);

9. Angina pectoris within the past 3 months;

10. Myocardial infarction, cerebrovascular accident, revascularization (PCI or other surgery), cardiac surgery, carotid artery or other large vessel surgery within the past 6 months;

11. Serious ventricular arrhythmias (sustained ventricular tachycardia or other conditions that the investigator considers necessary to exclude);

12. 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);

13. 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;

14. Systolic blood pressure < 90 mmHg or > 160 mmHg;

15. Serum K + < 3.2 mmol/L or > 5.5 mmol/L;

16. 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;

17. 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;

18. The investigator judges that the survival time is expected to be less than 6 months;

19. Participated in any drug clinical trials within the first 3 months;

20. Severe neurological disease (Alzheimer's disease, progressive parkinsonism);

21. 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.

Related Conditions & MeSH terms

• Chronic Systolic Heart Failure
• Heart Failure
• Heart Failure, Systolic
• Systolic Murmurs
• Ventricular Remodeling

Intervention

Drug:
• Neucardin
10 days IV infusion of 0.6 ug/kg/day
• Placebo
10 days IV infusion of 0 ug/kg/day

Locations

Country	Name	City	State
China	Ansteel Group Genral Hospital	Anshan	Liaoning
China	Anyang People's Hospital (Anyang Central Hospital)	Anyang	Henan
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	Fuwai Hospital Chinese Academy of Medical Sciences	Beijin	Beijing
China	Beijing Anzhen Hospital , Capital Medical University	Beijing	Beijing
China	Beijing Chao-Yang 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	Benxi Central Hospital	Benxi	Liaoning
China	China-Japan Union Hospital of Jilin University	Changchun	Jilin
China	Jilin University Second Hospital	Changchun	Jilin
China	The First Hospital of Jilin University	Changchun	Jilin
China	People's Hospital of Hunan Provincial	Changsha	Hunan
China	Changzhou No.2 People's Hospital	Changzhou	Jiansu
China	The First People's Hospital of Changzhou	Changzhou	Jiansu
China	The Fifth People's Hospital of Chengdu	Chengdu	Sichuan
China	Chenzhou First People's Hospital	Chenzhou	Huanan
China	Chongqing Emergency Medical Center (Chongqing Fourth People's Hospital)	Chongqing	Chongqing
China	Chongqing University Three Gorges Hospital	Chongqing	Chongqing
China	The First Affiliated Hospital of Dali University	Dali	Yunnan
China	The First Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Zhongshan Hospital Affiliated to Dalian University	Dalian	Liaoning
China	Daqing Oilfield General Hospital	Daqing	Heilongjiang
China	First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Harbin Medical University	Ha'erbin	Heilongjiang
China	Haikou People's Hospital	Haikou	Hainan
China	Hainan Provincial People's Hospital	Haikou	Hainan
China	The First Affiliated Hospital , Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Affiliated Hospital of Hangzhou Normal University	Hanzhou	Zhejiang
China	Sir Run Run Shaw Hospital	Hanzhou	Zhejiang
China	Nanyang Second People's Hospital	Henan	Nanyang
China	South China University Affiliated South China Hospital	Hengyang	Hunan
China	The Second Affiliated Hospital of Nanhua University	Hengyang	Hunan
China	Heze Municipal Hospital	Heze	Shandong
China	Huai'an First People's Hospital	Huai'an	Jiansu
China	Jiaxing First Hospital	Jiaxing	Zhejiang
China	Guangdong Jieyang People's Hospital	Jieyang	Guangdong
China	Jinan Central Hospital	Jinan	Shandong
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Shandong Province Qianfoshan Hospital	Jinan	Shandong
China	Affiliated Hospital of Jining Medical College	Jining	Shangdong
China	Jining first people's hospital	Jining	Shangdong
China	Huaihe Hospital of Henan University	Kaifeng	Henan
China	Fuwai Yunnan Cardiovascular Hospital	Kunming	Yunnan
China	The First People's Hospital of Yunnan Province	Kunming	Yunnan
China	Linyi People's Hospital	Linyi	Shandong
China	Liuzhou worker's hospital	Liuzhou	Guangxi Zhuang Autonomous Region
China	Longyan First Hospital	Longyan	Fujian
China	First Affiliated Hospital of Henan University of Science and Technology	Luoyang	Henan
China	Luoyang Central Hospital	Luoyang	Henan
China	Maoming people's hospital	Maoming	Guangdong
China	Mianyang Central Hospital	Mianyang	Sichuan
China	Jiangxi Provincial People's Hospital	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiansu
China	Zhongda Hospital Southeast University	Nanjing	Jiansu
China	People's Hospital of Guangxi Zhuang Autonomous Region	Nanning	Guangxi Zhuang Autonomous Region
China	Nanyang Central Hospital	Nanyang	Henan
China	Nanyang First People's Hospital	Nanyang	Henan
China	Ningbo Huamei Hospital, University of Chinese Academy of Sciences (Ningbo Second Hospital)	Ningbo	Zhejiang
China	The First Hospital of Ningbo	Ningbo	Zhejiang
China	General Hospital of Puyang Oilfield	Puyang	Henan
China	Qiqihar first hospital	Qiqihar	Heilongjiang
China	Sanmenxia Central Hospital	Sanmenxia	Henan
China	Putuo District Central Hospital of Shanghai	Shanghai	Shanghai
China	Shanghai Baoshan District Wusong Central Hospital	Shanghai	Shanghai
China	First People's Hospital of Shangqiu	Shangqiu	Henan
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	The First Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiansu
China	The Suzhou Municipal Hospital	Suzhou	Jiansu
China	Tai'an City Central Hospital	Tai'an	Shandong
China	Shanxi Provincial Cardiovascular Hospital	Taiyuan	Shanxi
China	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	First affiliated hospital of Wenzhou medical university	Wenzhou	Zhejiang
China	People's Hospital of Wuhan University	Wuhan	Hubei
China	Wuhan Wuchang Hospital	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	The First Affiliated Hospital of Xi 'an Jiaotong University	Xi'an	Shanxi
China	Xi'an Gaoxin Hospital	Xi'an	Shanxi
China	Xiamen Cardiovascular Hospital Xiamen University	Xiamen	Fujian
China	Xiangyang Central Hospital	Xiangyang	Hubei
China	Xiangyang first people's hospital	Xiangyang	Hubei
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 First Affiliated Hospital of Xinxiang Medical College	Xinxiang	Henan
China	Xinxiang central hospital	Xinxiang	Henan
China	Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiansu
China	Xuzhou Central Hospital	Xuzhou	Jiansu
China	Subei people's hospital	Yangzhou	Jiansu
China	Yueyang Central Hospital	Yueyang	Hunan
China	Zaozhuang municipal hospital	Zaozhuang	Shangdong
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	Zibo Municipal Hospital	Zibo	Shandong

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	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)	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
Secondary	Response rate at 35 day of left ventricular end systolic volume index (LVESVI) improvement greater than or equal to 25 ml/m2;	Response rate at 35 day of LVESVI improvement greater than or equal to 25 ml/m2;	Day 35
Secondary	Response rate at 35 day of left ventricular end diastolic volume index (LVEDVI) improvement greater than or equal to 25 ml/m2;	Response rate at 35 day of LVEDVI improvement greater than or equal to 25 ml/m2;	Day 35
Secondary	Change from baseline in left ventricular ejection fraction (LVEF) at 35 days;	Change from baseline in LVEF at 35 days;	Day 35
Secondary	Change from baseline in left ventricular end systolic volume (LVESV) at 35 days;	Change from baseline in LVESV at 35 days;	Day 35
Secondary	Change from baseline in left ventricular end diastolic volume (LVEDV) at 35 days;	Change from baseline in LVEDV at 35 days;	Day 35
Secondary	Change from baseline in LVESVI and LVEDVI at 35 days;	Change from baseline in LVESVI and LVEDVI at 35 days;	Day 35
Secondary	90-day response rate of LVESVI improved greater than or equal to 25 ml/m2;	90-day response rate of LVESVI improved greater than or equal to 25 ml/m2;	Day 90
Secondary	90-day response rate of LVEDVI 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
Secondary	90-day response rate of LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time;	90-day response rate of LVESVI and LVEDVI improved greater than or equal to 20 ml/m2 at the same time;	Day 90
Secondary	Change from baseline in LVEF at 90 days;	Change from baseline in LVEF at 90 days;	Day 90
Secondary	Change from baseline in LVESV at 90 days;	Change from baseline in LVESV at 90 days;	Day 90
Secondary	Change from baseline in LVEDV at 90 days;	Change from baseline in LVEDV at 90 days;	Day 90
Secondary	Change from baseline in LVESVI and LVEDVI at 90 days;	Change from baseline in LVESVI and LVEDVI at 90 days;	Day 90
Secondary	Change from baseline in New York Heart Association (NYHA) at 35 and 90 days;	Change from baseline in NYHA at 35 and 90 days;	Day 35 and Day 90
Secondary	Change from baseline in quality of life at 35 and 90 days;	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.	Day 35 and Day 90
Secondary	Mortality during the study period;	Mortality during the study period;	Through study completion, an estimation of average of 1 year