Clinical trial NCT01917149: Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
Official title: Efficacy and Safety Study of Supramaximal Titrated Inhibition of RAAS in Idiopathic Dilated Cardiomyopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dilated Cardiomyopathy
Keywords: Dilated cardiomyopathy
High dose ACEI/ARB
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2013-08-06
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: All cause death or admission for heart failure
timeFrame: 48 months after enrollment
Secondary outcomes:
measure: Changes in NYHA functional class
timeFrame: 6,12, 24 and 36 months after enrollment
measure: Left-ventricular ejection fraction
timeFrame: 6,12, 24 and 36 months after enrollment
measure: Left-ventricular end-diastolic diameter
timeFrame: 6, 12 , 24 and 36 months after enrollment
Other outcomes:
measure: All-cause mortality
timeFrame: 48 months after enrollment
measure: Cardiovascular death
timeFrame: 48 months after enrollment
measure: All-cause hospital admission
timeFrame: 48 months after enrollment
measure: Heart failure admission
timeFrame: 48 months after enrollment
measure: changes in mitral regurgitation
timeFrame: 12, 24 and 36 months after enrollment
measure: wall-motion score index
timeFrame: 12, 24 and 36 months after enrollment
measure: Adverse events
timeFrame: 48 months after enrollment
Locations:
city: Xi'an
country: China
facility: Xijing Hospital, Department of Cardiology
Study officials:
affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University
name: Zheng He, MD, phD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiology, Xijing Hospital, Fourth Military Medical University
name: Qiujun Yu, MD, phD
role: PRINCIPAL_INVESTIGATOR
References:
citation: He Z, Sun Y, Gao H, Zhang J, Lu Y, Feng J, Su H, Zeng C, Lv A, Cheng K, Li Y, Li H, Luan R, Wang L, Yu Q. Efficacy and safety of supramaximal titrated inhibition of renin-angiotensin-aldosterone system in idiopathic dilated cardiomyopathy. ESC Heart Fail. 2015 Dec;2(4):129-138. doi: 10.1002/ehf2.12042. Epub 2015 Jul 14.