A Phase Ⅲ Study of Extended-Release Carvedilol Sulfate for the Treatment of Heart Failure

Study Overview
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Brief Summary
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The aim of present study is to evaluate the efficacy and safety of Extended-Release Carvedilol Sulfate versus Sustained-release Metoprolol Succinate in Patients With Mild or Moderate Chronic Heart Failure.

Official Title
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Efficacy and Safety Comparison of Extended-Release Carvedilol Sulfate and Sustained-release Metoprolol Succinate in Patients With Heart Failure

Conditions
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Heart Failure

Intervention / Treatment
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* Drug: Extended-Release Carvedilol Sulfate
* Drug: Sustained-release Metoprolol Succinate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or Females Aged from 18 to 75 years New York Heart Association(NYHA) classification Ⅱ-Ⅲ At screening, subject has an LVEF<0.45 Have received optimal therapy with an Angiotensin converting enzyme inhibitors or angiotensin receptor blocker for 4 weeks before enrollment Subjects with symptoms of Stable heart failure do not need intravenous injection diuretics,cardiac inotropes or vasodilators Willing to provide written informed consent Exclusion Criteria: Current treatment on any Class I or III antiarrhythmic, except amiodarone or beta-blockers Current treatment on calcium antagonists except for long-acting dihydropyridine agents Have a history of acute coronary syndrome,cerebral apoplexy or transient ischemic attack with 3 months Have a history of cardio-vascular surgery or other vessel operations with 3 months Have a history of sustained ventricular tachycardia or ventricular fibrillation with 3 months Have a plan to receive coronary revascularization or heart transplantation Uncontrolled ventricular arrhythmias (not controlled with antiarrhythmic therapy or an implantable defibrillator) Subjects with uncorrected primary obstructive or severe regurgitative valvular disease，nondilated (restrictive) or hypertrophic cardiomyopathy Sitting systolic blood pressure≤90mmHg (based on an average of 3 readings) Current decompensated heart failure Second or third degree heart block，or sick sinus syndrome，a pacemaker is not placed Contraindication to vasodilators Have a history of cardiac resynchronization therapy or Have received cardioverter defibrillator or pacemaker with 1 month Resting heart rate<50 beats per minute(based on the average of 3 readings) Elevated liver enzymes (alanine aminotransferase or aspartate aminotransferase levels greater than 3 times upper limit of normal) Serum creatinine levels greater than 2 times upper limit of normal Current clinical evidence of obstructive pulmonary disease (e.g., asthma or bronchitis) requiring inhaled or oral bronchodilator or steroid therapy History of drug sensitivity or allergic reaction to alpha or beta-blockers Contraindication or intolerance to beta-blockers Pregnant or lactating women and women planning to become pregnant Has any systemic disease, including cancer, with reduced life expectancy (<12 months) Use of an investigational drug within 30 days of enrollment Participation in an investigational device trial within 30 days of enrollment Known drug or alcohol abuse 1 year prior to enrollment Has a history of psychological illness/condition that interferes with ability to understand or complete requirements of the study In the opinion of the investigator the subject is known to be noncompliant with prescribed medication regimen

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: Extended-Release Carvedilol Sulfate<br>18-72mg/d,po | Drug: Extended-Release Carvedilol Sulfate<br> <br> |
| Active Comparator: Sustained-release Metoprolol Succinate<br>11.875-190mg/d,po | Drug: Sustained-release Metoprolol Succinate<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 ejection fraction(LVEF) by ultrasound cardiogram |  | Baseline and Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Left Ventricular End Systolic Volume Index |  | Baseline and Week 36 | 
| Change From Baseline in Left Ventricular End Diastolic Volume Index |  | Baseline and Week 36 | 
| Incidence of Hospitalizations From Exacerbation of Heart Failure |  | Baseline and Week 36 | 
| Incidence of Hospitalizations From All Causes |  | Baseline and Week 36 | 
| Incidence of Deaths From All Causes |  | Baseline and Week 36 | 
| Change From Baseline in New York Heart Association（NYHA）classification |  | Baseline and Week 36 |