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

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

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.

Study Overview

• Status: Unknown
• Conditions: Heart Failure
• Intervention / Treatment: Drug: Extended-Release Carvedilol Sulfate; Drug: Sustained-release Metoprolol Succinate

• Study Type: Interventional
• Enrollment (Anticipated): 316
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100029
    • Recruiting
    • Beijing Anzhen Hospital
  • Beijing, China, 100029
    • Recruiting
    • China-Japan Friendship Hospital
  • Beijing, China, 100053
    • Recruiting
    • Xuan Wu hospital affiliated to Capital Medical University
  • Beijing, China
    • Recruiting
    • Beijing Tongren Hospital Affiliated to Capital Medical University
  • Gansu
    • Lanzhou, Gansu, China
      • Recruiting
      • Gansu Provincial Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • The Second Xiangya Hospital of Central South University
    • Changsha, Hunan, China
      • Recruiting
      • The Third Xiangya Hospital Of Central South University
  • Jiangsu
    • Yangzhou, Jiangsu, China, 225001
      • Recruiting
      • Northern Jiangsu People's Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Recruiting
      • Shengjing Hospital of China Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The First Affiliated Hospital of College of Medicine, Zhejiang University
    • Taizhou, Zhejiang, China
      • Recruiting
      • Taizhou Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Extended-Release Carvedilol Sulfate; 18-72mg/d,po	Drug: Extended-Release Carvedilol Sulfate
ACTIVE_COMPARATOR: Sustained-release Metoprolol Succinate; 11.875-190mg/d,po	Drug: Sustained-release Metoprolol Succinate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in left ventricular ejection fraction(LVEF) by ultrasound cardiogram	Baseline and Week 36

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ANTICIPATED): February 1, 2015

Study Registration Dates

• First Submitted: December 10, 2013
• First Submitted That Met QC Criteria: December 10, 2013
• First Posted (ESTIMATE): December 16, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): December 16, 2013
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Antioxidants; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Metoprolol; Carvedilol
• Other Study ID Numbers: KWDLHF2012