Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets （FIRST）

Study Overview
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Brief Summary
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Ivabradine acts by inhibiting the ionic If current that modulates the pacemaker activity of sinoatrial node cells. The aim of present study is to evaluate the efficacy and safety of IvabRadine hemisulfate Sustained-release Tablets versus placebo in patients with moderate to severe chronic systolic heart failure.

Official Title
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Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets （FIRST）

Conditions
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Chronic Systolic Heart Failure

Intervention / Treatment
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* Drug: IvabRadine hemisulfate Sustained-release Tablets
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged from 18 to 75 years, males or females Willing to provide written informed consent NYHA Class II, III, or IV for≥4 weeks, in stable clinical condition for ≥4 weeks Optimized and unchanged chronic heart failure medications and dosages for≥4 weeks Sinus rhythm with resting heart rate≥70 b.p.m. Left-ventricular systolic dysfunction, with ejection fraction≥40% documented within previous 1 month Exclusion Criteria: Unstable cardiovascular condition(for example, hospital admission for worsening heart failure) Recent (<2 months) myocardial infarction or recent or scheduled coronary revascularization Stroke or transient cerebral ischaemia within previous 4 weeks Severe primary valvular disease Scheduled surgery of valvular heart disease Active myocarditis Congenital heart diseases peripartum cardiomyopathy hyperthyroid heart disease On list for cardiac transplantation Cardiac resynchronization therapy started within previous 6 months Pacemaker with atrial or ventricular pacing (except biventricular pacing)˃40% of the time, or with stimulation threshold at the atrial or ventricular level˃60 b.p.m. Permanent atrial fibrillation or flutter Sick sinus syndrome, sinoatrial block, second and third degree atrio-ventricular block History of symptomatic or sustained (≥30 s) ventricular arrhythmia unless a cardioverter/defibrillator implanted Cardioverter/defibrillator shock within previous 6 months Family history or congenital long QT syndrome or treated with selected QT-prolonging products(except amiodarone) Contraindication or intolerance to ivabradine or lactulose Severe or uncontrolled hypertension (SBP≥180 mmHg or DBP≥110 mmHg) known anaemia(Hb<100 g/L) Known moderate or severe liver disease(ALT/AST˃3ULN), known severe renal disease(Cr˃2ULN) Pregnant or lactating women and women planning to become pregnant Use of an investigational drug within 30 days of enrollment Has a history of psychological illness/condition that interferes with ability to understand or complete requirements of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IvabRadine hemisulfate Sustained-release Tablets<br>5-15mg qd | Drug: IvabRadine hemisulfate Sustained-release Tablets<br> <br> |
| Placebo Comparator: placebo<br>5-15mg qd | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Left Ventricular End Systolic Volume Index by ultrasound cardiogram |  | baseline and week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Left Ventricular End Diastolic Volume Index and left ventricular ejection fraction(LVEF) |  | baseline and week 32 | 
| incidence of hospital admission for worsening heart failure、any cardiovascular hospital admission、 cardiovascular mortality、all-cause mortality |  | baseline and week 32 | 
| change from baseline in distance of 6-minute walking test |  | baseline and week 32 | 
| change from baseline in heart rate |  | baseline and week 32 | 
| change from baseline in scores of Kansas City Cardiomyopathy Questionnaire |  | baseline and week 32 | 
| change from baseline in NT-proBNP |  | baseline and week 32 |