Brief Title
Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
Official Title
Efficacy and Safety Study of Supramaximal Titrated Inhibition of RAAS in Idiopathic Dilated Cardiomyopathy
Brief Summary
Dilated cardiomyopathy (DCM) is a poorly understood cause of systolic heart failure and is the most common indication for heart transplantation worldwide. Despite advances in medical and device therapy, the 5-year mortality of patients with DCM remains high. Patients diagnosed of dilated cardiomyopathy with a NYHA functional class of II to IV and left ventricular ejection fraction(LVEF) <35% were selected for randomized controlled study of the efficacy and safety of high dose Renin-angiotensin system (RAS) inhibitor (benazepril or valsartan), in comparison with low dose RAS inhibitor(benazepril or valsartan) and standard beta-adrenergic blocker therapy (metoprolol). The primary endpoint was all cause death or admission for heart failure. Additional prespecified outcomes included all-cause death, cardiovascular death, all-cause admission, heart failure admission. Secondary cardiovascular outcomes included the changes from baseline to the last available observation after treatment in NYHA functional class, quality-of-life scores, LVEF, LVEDD, mitral regurgitation and wall-motion score index assessed by ECG. Adverse events were reported during in-hospital observation and follow-ups.
Study Phase
Phase 4
Study Type
Interventional
Primary Outcome
All cause death or admission for heart failure
Secondary Outcome
Changes in NYHA functional class
Condition
Dilated Cardiomyopathy
Intervention
Benazepril
Study Arms / Comparison Groups
Metoprolol
Description: Patients in the metoprolol group were started on 11.875-23.75mg of metoprolol succinct extended-release tablet once daily (11.875mg was recommended for patients with NYHA functional classes III-IV), and then doses were doubled every 2 weeks to achieve asymptomatic bradycardia (50-60 bpm of heart rate) over 4-6 weeks. Investigators were encouraged to up-titrate metoprolol to a maximum dose of 190mg whenever possible.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
480
Start Date
March 2005
Completion Date
December 2013
Primary Completion Date
July 2013
Eligibility Criteria
Inclusion Criteria: - Diagnosis of dilated cardiomyopathy - Left ventricular ejection fraction < 35% - NYHA Functional classes of II-IV - Symptomatic but not rapidly deteriorating 1 month before enrollment - Signed informed consent Exclusion Criteria: - Contradictions and intolerance of the studied drugs: - supine systolic arterial blood pressure < 90 mmHg, - renal artery stenosis >50%, - pregnancy or lactation, - impaired renal function (estimated glomerular filtration rate < 60 ml/min/1.73m2, - impaired liver function (total bilirubin >2 times upper limit of normal, - serum aspartate AST or alanine ALT >3 times the upper limit of normal), - hemoglobin less than 8 mg/dl, hyperkalaemia (serum potassium >5.5mmol/l), - obstructive lung disease, - advanced atrioventricular block, - any co-morbidity with impact on survival, and - known intolerance to benazepril, valsartan and metoprolol succinate; - HF secondary to a known cause: - coronary artery disease based on coronary angiography (≥50% stenosis in ≥1 of the major coronary arteries) and/or a history of myocardial infarction or angina pectoris, - acute or subacute stage of myocarditis, - primary valve disease, - diabetes mellitus, - excessive use of alcohol or illicit drugs; - Expected or performed cardiac resynchronization therapy and heart transplantation.
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Zheng He, MD, phD, ,
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT01917149
Organization ID
SIRAAS-DC
Responsible Party
Principal Investigator
Study Sponsor
Xijing Hospital
Study Sponsor
Zheng He, MD, phD, Principal Investigator, Department of Cardiology, Xijing Hospital, Fourth Military Medical University
Verification Date
May 2014