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Evaluate the Effect of Injectable Neucardin on the Cardiac Function of Subjects With Chronic Systolic Heart Failure

Phase 3
Completed
Conditions
Chronic Systolic Heart Failure
Interventions
Drug: Recombinant human Neuregulin for injection
Drug: Placebo
Registration Number
NCT04468529
Lead Sponsor
Zensun Sci. & Tech. Co., Ltd.
Brief Summary

A multi-center, randomized, double-blind, placebo-controlled phase III clinical trial to evaluate the effect of injectable Neucardin on the heart function in male patients with NT-proBNP ≤ 1700 pg/ml and female patients with NT-proBNP ≤ 4000 pg/ml, NYHA 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 domestic clinical research site, and a total of 140 subjects will be enrolled, including 70 subjects in the investigational drug group and 70 subjects in the placebo group.

Primary endpoint: LVESVI change from baseline on day 30 Secondary endpoints: LVEF Change from baseline on day 30 and day 90. LVESV, LVEDV, LVEDVI change from baseline on day 30. LVESV, LVESVI, LVEDV, LVEDVI change from baseline on day 90. NT-proBNP change from baseline on day 30 and day 90. NYHA class change from baseline on day 30 and day 90.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
154
Inclusion Criteria
  1. Aged 18-75 years, male or female;
  2. Confirmed diagnosis of heart failure, in stable condition currently, NYHA class II-III, left ventricular ejection fraction (LVEF)≤40% (measured by echocardiography with modified Simpson's method at Screening 1, and measured by CMR at Screening 2 and baseline);
  3. Male NT-proBNP ≤1700 pg/ml or female NT-proBNP≤4000 pg/ml (detected by Roche kit in the central laboratory at screening 1);
  4. Receiving standard basic therapeutic medication for heart failure for more than 3 months, at the target dose or maximum tolerated dose for more than 1 month, or no change in dose within the last 1 month;
  5. Understand and sign the informed consent form.
Exclusion Criteria
  1. Atrial fibrillation during the screening period;
  2. Conditions limiting CMR examination, such as installation of pacemakers, ICDs, CRTs or other similar devices contraindicated for CMR, or have claustrophobia;
  3. Hypertrophic cardiomyopathy with outflow tract obstruction, constrictive pericarditis, significant and uncorrected valvular heart disease (severe regurgitation or severe stenosis or valvular disease requiring surgery), congenital heart disease requiring surgery but not yet undergoing surgical treatment, primary pulmonary hypertension or secondary severe pulmonary hypertension (≥ 70 mmHg);
  4. Right heart failure due to lung disease;
  5. Subjects with chronic heart failure complicated with acute hemodynamic disturbance or acute decompensation within recent 1 month (symptoms and signs indicate chronic heart failure is aggravated, and intravenous drug therapy may be required);
  6. Angina pectoris within 3 months;
  7. Myocardial infarction within the past 6 months;
  8. Cerebrovascular accident, revascularization (PCI or other surgery), cardiac surgery, carotid artery or other large vessel surgery within the past 6 months;
  9. Prepare to install pacemaker, ICD, CRT or other similar devices within 6 months;
  10. History of heart transplantation, use of ventricular assist device (VAD) or preparation for heart transplantation, VAD;
  11. Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within the past 12 months;
  12. Serious arrhythmia (sustained ventricular tachycardia or other conditions meet the criteria according to the investigator's judgement );
  13. Clinical diagnosis of pericardial effusion, pleural effusion or B ultrasound showed pericardial effusion (greater than 50ml or 3 mm) or pleural effusion (greater than 200ml or 10 mm);
  14. Liver or kidney dysfunction, chronic liver disease may have a potential impact on liver function, non-heart failure induced bilirubin or alkaline phosphatase > 2 times the upper limit of normal, aspartate aminotransferase or alanine aminotransferase > 3 times the upper limit of normal, eGFR calculated using the MDRD method < 30 ml/min/1.73m2 ;
  15. Systolic blood pressure < 90 mmHg or > 160 mmHg;
  16. Blood K + < 3.2 mmol/L or > 5.5 mmol/L;
  17. Subjects with an absolute change in LVEF > 5% as detected by CMR between screening 2 and baseline;
  18. Women of childbearing age who are planning to become pregnant within 2 years (women of childbearing age are defined as all women with physiological capability to become pregnant), and pregnant or lactating women;
  19. Patients whose survival time is expected to be less than 6 months as judged by the investigator;
  20. Those who have participated in any drug clinical trial within the previous 3 months;
  21. Severe neurological disorders (Alzheimer's disease, progressive parkinsonism);
  22. The subjects with tumor history or is suffering from tumor now, or with precancerous lesions confirmed by pathological examination (such as breast ductal carcinoma in situ, or cervical dysplasia), or with malignant mass found by examination (physical examination, X-ray examination or B ultrasound examination or other means);
  23. The subjects with proliferative glands or adenomas that are found to have endocrine activity that affects cardiac function or endocrine function detected by examinations (physical examination, X-ray examination, B ultrasound examination or other means), such as pheochromocytoma, thyromegaly, etc. (patients with euthyroid thyroid or normal thyroid function do not need to be excluded);
  24. The subject, in the judgment of the Investigator, is unable to complete the study or to comply with the requirements of the study (for administrative or other reasons).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Investigational drug groupRecombinant human Neuregulin for injectionInjectable Neucardin + standard basic therapeutic medication
Placebo groupPlaceboplacebo + standard basic therapeutic medication
Primary Outcome Measures
NameTimeMethod
Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline on day 30Day 30

Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline

Secondary Outcome Measures
NameTimeMethod
Left Ventricular Ejection Fraction(LVEF) Change from baseline on day 30 and day 90Day 30 and Day 90

Left Ventricular Ejection Fraction(LVEF) Change from baseline

Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline on day 90Day 90

Left Ventricular End-Systolic Volume Index(LVESVI) change from baseline

Left Ventricular End-Systolic Volume(LVESV)change from baseline on day 30 and day 90Day 30 and Day 90

Left Ventricular End-Systolic Volume(LVESV)change from baseline

Left Ventricular End-Diastolic Volume(LVEDV)change from baseline on day 30 and day 90Day 30 and Day 90

Left Ventricular End-Diastolic Volume(LVEDV)change from baseline

Left Ventricular End-Diastolic Volume Index(LVEDVI )change from baseline on day 30 and day 90Day 30 and Day 90

Left Ventricular End-Diastolic Volume Index(LVEDVI )

N-Terminal pro-Brain Natriuretic Peptide(NT-proBNP) change from baseline on day 30 and day 90Day 30 and Day 90

N-Terminal pro-Brain Natriuretic Peptide(NT-proBNP) change from baseline

New York Heart Association(NYHA) class change from baseline on day 30 and day 90Day 30 and day 90

New York Heart Association(NYHA) class change from baseline

Trial Locations

Locations (29)

The Second Xiangya Hospital of Central South University

🇨🇳

Changsha, China

The First Affiliated Hospital of Dalian Medical University

🇨🇳

Dalian, China

Jinan Central Hospital

🇨🇳

Jinan, China

Shandong Province QianFoshan Hospital

🇨🇳

Jinan, China

Qilu Hospital of Shandong University

🇨🇳

Jinan, China

Shanghai JiaoTong University Ruijing Hospital

🇨🇳

Shanghai, China

First Hospital of Shanxi Medical University

🇨🇳

Taiyuan, China

Shanxi Cardiovascular Hospital

🇨🇳

Taiyuan, China

The First Affiliated Hospital of Zhengzhou University

🇨🇳

Zhengzhou, China

People's Hospital of Tianjin

🇨🇳

Tianjin, China

Chinese PLA General Hospital

🇨🇳

Beijing, China

First Affiliated Hospital,Sun Yat-sen University

🇨🇳

Guangzhou, China

Hainan General Hospital

🇨🇳

Hainan, China

Hunan Provincial People's Hospital

🇨🇳

Hunan, China

Luoyang Center Hospital

🇨🇳

Luoyang, China

Shanghai Putuo District Central Hospital

🇨🇳

Shanghai, China

Shengjing Hospital of China Medical University

🇨🇳

Shenyang, China

The First Affiliated Hospital of Soochow University

🇨🇳

Suzhou, China

Shanghai First People's Hospital

🇨🇳

Shanghai, China

Affiliated Drum Tower Hospital, Medical School of Nanjing University

🇨🇳

Nanjing, China

The Second Hospital of Tianjin Medical University

🇨🇳

Tianjin, China

Beijing Chaoyang Hospital of Capital Medical University

🇨🇳

Beijing, China

Fuwai hospital chinese Academy of Medical Sciences

🇨🇳

Beijing, China

China-Japan Union Hospital of Jilin University

🇨🇳

Changchun, China

Beijing Friendship Hospital of Capital Medical University

🇨🇳

Beijing, China

Chongqing University Three Gorges Hospital

🇨🇳

Chongqing, China

The First Hospital of Jilin University

🇨🇳

Changchun, China

Haikou People's Hospital

🇨🇳

Haikou, China

Guangdong Provincial People's Hospital

🇨🇳

Guangzhou, China

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