Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy

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 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

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