Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
|ClinicalTrials.gov Identifier: NCT01917149|
Recruitment Status : Completed
First Posted : August 6, 2013
Last Update Posted : May 19, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Dilated Cardiomyopathy||Drug: Benazepril Drug: Valsartan Drug: Metoprolol||Phase 4|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||480 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Efficacy and Safety Study of Supramaximal Titrated Inhibition of RAAS in Idiopathic Dilated Cardiomyopathy|
|Study Start Date :||March 2005|
|Actual Primary Completion Date :||July 2013|
|Actual Study Completion Date :||December 2013|
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.
Experimental: Low-dose valsartan
Patients randomized to low dose valsartan receive valsartan 80 mg until study completion.
Experimental: Low dose Benazepril
Patients randomized to low dose Benazepril receive Benazepril 10 mg until study completion.
Experimental: High dose valsartan
Patients randomized to high-dose valsartan were started on valsartan 80mg twice daily, and uptitrated to target doses within 7 days under in-hospital observation. The target high doses of valsartan is determined by left-ventricular end-diastolic diameter (LVEDD) (the maximal value of anteroposterior and lateral diameters) obtained by ECG at the randomization visit. A target dose of valsartan 320mg, 480mg, 640mg daily were assigned to patients with LVEDD of 50-59, 60-69, ≥70 mm respectively.
Experimental: High dose Benazepril
Patients randomized to high-dose benazepril were started on benazepril 10mg twice daily, and uptitrated to target doses within 7 days under in-hospital observation. The target high doses of benazepril is determined by left-ventricular end-diastolic diameter (LVEDD) (the maximal value of anteroposterior and lateral diameters) obtained by ECG at the randomization visit. A target dose of benazepril 40mg, 60mg, 80mg daily were assigned to patients with LVEDD of 50-59, 60-69, ≥70 mm respectively.
- All cause death or admission for heart failure [ Time Frame: 48 months after enrollment ]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 ]
- Left-ventricular ejection fraction [ Time Frame: 6,12, 24 and 36 months after enrollment ]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 ]
- All-cause mortality [ Time Frame: 48 months after enrollment ]
- Cardiovascular death [ Time Frame: 48 months after enrollment ]
- All-cause hospital admission [ Time Frame: 48 months after enrollment ]
- Heart failure admission [ Time Frame: 48 months after enrollment ]
- changes in mitral regurgitation [ Time Frame: 12, 24 and 36 months after enrollment ]
- wall-motion score index [ Time Frame: 12, 24 and 36 months after enrollment ]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 ]Hypotension Hyperkalaemia Renal impairment Liver dysfunction Nonfatal stroke Angioedema
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01917149
|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|