High Dose RAS Inhibitor for Dilated Cardiomyopathy
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 near 50%.
Patients diagnosed of dilated cardiomyopathy with a NYHA functional class of III 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, in comparison with low dose RAS inhibitor and standard beta-adrenergic blocker therapy. The major outcome measures include LVEF, LV end-diastolic diameter, exercise capacity, all-cause/cardiovascular mortality, and all-cause/heart failure hospital admission.
Drug: Standard medicaiton without ACEI or ARB
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Efficacy and Safety Study of High Dose RAS Inhibitor in Reversing Cardiac Remodeling in Dilated Cardiomyopathy|
- All cause death or admission for heart failure [ Time Frame: 48 months after enrollment ] [ Designated as safety issue: No ]Admission for heart failure was defined as a minimum of 24 h inpatient admission to any health-care facility, with the primary cause being treated for worsening heart failure and during which an additional diuretic drug, intravenous or oral nitrate, or intravenous inotropic agent was given.
- Changes in NYHA functional class [ Time Frame: 6,12, 24 and 36 months after enrollment ] [ Designated as safety issue: No ]
- Left-ventricular ejection fraction [ Time Frame: 6,12, 24 and 36 months after enrollment ] [ Designated as safety issue: No ]Left ventricular ejection fraction (LVEF) were calculated from measurements of left ventricular end diastolic and end systolic volumes in apical 4 and 2 chamber views using the modified Simpson's rule according to current guidelines
- Left-ventricular end-diastolic diameter [ Time Frame: 6, 12 , 24 and 36 months after enrollment ] [ Designated as safety issue: No ]
- All-cause mortality [ Time Frame: 48 months after enrollment ] [ Designated as safety issue: No ]
- Cardiovascular death [ Time Frame: 48 months after enrollment ] [ Designated as safety issue: No ]
- All-cause hospital admission [ Time Frame: 48 months after enrollment ] [ Designated as safety issue: No ]
- Heart failure admission [ Time Frame: 48 months after enrollment ] [ Designated as safety issue: No ]
- changes in mitral regurgitation [ Time Frame: 12, 24 and 36 months after enrollment ] [ Designated as safety issue: No ]
- wall-motion score index [ Time Frame: 12, 24 and 36 months after enrollment ] [ Designated as safety issue: No ]Wall motion score index (WMSI) was analyzed using an 11 segments model (3) (basal lateral, middle lateral, basal inferior, middle inferior, basal posterior interventricular septum, middle posterior interventricular septum, basal anterior free wall, middle anterior free wall, basal anterior interventricular septum, middle anterior interventricular septum and apex) with six segments each assigned to anterior and inferior regions, the apex being common. The motion of individual segments was graded as follows: normal 0, hypokinesia 1, akinesia 2, and dyskinesia 3. Global systolic wall motion score was calculated by dividing the total score by the number of segments analyzable. Results were only included when at least four segments from each of the anterior and inferior regions were analyzable. The lowest value of segment motion was chosen from the recorded motion amplitude of all 11 segments
- Adverse events [ Time Frame: 48 months after enrollment ] [ Designated as safety issue: Yes ]Hypotension Hyperkalaemia Renal impairment Liver dysfunction Nonfatal stroke Angioedema
|Study Start Date:||March 2004|
|Estimated Study Completion Date:||December 2013|
|Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
Active Comparator: Low dose ACEI/ARB
Patients randomized to low dose ACEI/ARB receive 1 tablet of ACEI or ARB daily until study completion. 1 tablet of ACEI or ARB is referred as Benazepril 10 mg or Valsartan 80mg.
|Drug: Benazepril Drug: Valsartan|
Active Comparator: standard therapy without ACEI or ARB
Medications were given in accordance with current guidelines for the management of patients with DCM. Investigators were encouraged to titrate β-blocker dosing to a maximum, whenever possible.A small starting dose of β-blockers (Metroprolol, Bisoprolol, or Carvedilol) was recommended for patients with NYHA functional classes III-IV.
|Drug: Standard medicaiton without ACEI or ARB|
Experimental: High dose ACEI/ARB
The target high dose of ACEI or ARB is determined by left-ventricular end-diastolic diameter (LVEDD) obtained by echocardiography at the randomization visit. A target dose of 2-3, 4-5, or 6-8 tablet of ACEI or ARB daily is assigned to patients with LVEDD of 50-59, 60-69, ≥70 cm respectively. The starting dose is 1 tablet twice daily, and dose is successively increased to target dose within 7 days under in-hospital observation. Dose regimen could be modified according to patient's tolerance. 1 tablet of ACEI or ARB is referred as Benazepril 10 mg, or Valsartan 80mg.
|Drug: Benazepril Drug: Valsartan|
|Xijing Hospital, Department of Cardiology|
|Xi'an, China, 710032|
|Principal Investigator:||Zheng He, MD, phD||Department of Cardiology, Xijing Hospital, Fourth Military Medical University|
|Principal Investigator:||Qiujun Yu, MD, phD||Department of Cardiology, Xijing Hospital, Fourth Military Medical University|