Effects of Ivabradine on Cardiovascular Events in Patients With Moderate to Severe Chronic Heart Failure and Left Ventricular Systolic Dysfunction. A Three-year International Multicentre Study

Study Overview
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Brief Summary
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The primary objective of this study is to demonstrate the superiority of ivabradine over placebo in the reduction of cardiovascular mortality or hospitalisation for worsening heart failure in patients with moderate to severe symptoms of chronic heart failure, a reduced left ventricular ejection fraction and currently receiving recommended therapy for this disease.

Conditions
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Chronic Heart Failure

Intervention / Treatment
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* Drug: Ivabradine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptomatic Chronic heart failure (NYHA II, III or IV) Left ventricular systolic dysfunction (LVEF ≤ 35%) Sinus rhythm and resting heart rate ≥ 70 bpm Optimal and unchanged CHF medications or dosages Exclusion Criteria: Unstable condition within previous 4 weeks Myocardial infarction or coronary revascularisation within previous 2 months Stroke or transient cerebral ischaemia within previous 4 weeks Congenital heart disease Severe valvular disease Active myocarditis Permanent atrial fibrillation or flutter

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivabradine<br> | Drug: Ivabradine<br>* 2.5mg, 5mg or 7.5mg tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo tablets to be taken orally twice daily, at 12-hours intervals, in the morning and in the evening during meals up to 42 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Composite Endpoint: First Event Among Cardiovascular Death (Including Death of Unknown Cause) or Hospitalization for Worsening Heart Failure. | Number of patients having experienced the Primary Composite Endpoint. | All over the study (up to 42 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiovascular Death | Component of the primary composite endpoint | From the date of randomization until the date of death, up to 42 months | 
| Hospitalisation for Worsening Heart Failure |  | From the date of randomization to the date of first documented hospitalisation, up to 42 months | 
| All-cause Mortality |  | From the date of randomisation to death, up to 42 months. | 
| Death From Heart Failure | Component of cardiovascular death | From the date of randomisation to death, up to 42 months. | 
| Hospitalisation for Any Cause |  | From the date of randomisation to the date of first documented hospitalisation, up to 42 months | 
| Hospitalisation for Cardiovascular Reason |  | From the date of randomisation to the first documented hospitalisation, up to 42 months | 
| Unplanned Hospitalisation for Any Cause |  | From the date of randomisation to the first documented hospitalisation, up to 42 months | 
| Unplanned Hospitalisation for CV Reason |  | From the date of randomisation to the first documented hospitalisation, up to 42 months. | 
| Secondary Composite Endpoint | CV death, hospitalisation for worsening HF or hospitalisation for non-fatal myocardial infarction | From the date of randomisation to the date of the first event, up to 42 months |