Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy

Dilated Cardiomyopathy Clinical Trial

Official title:

Efficacy and Safety Study of Supramaximal Titrated Inhibition of RAAS in Idiopathic Dilated Cardiomyopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01917149
• Other study ID #: SIRAAS-DC
• Status: Completed
• Phase: Phase 4
• First received: July 30, 2013
• Last updated: May 16, 2014
• Start date: March 2005
• Est. completion date: December 2013

Study information

• Verified date: May 2014
• Source: Xijing Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 480
• Est. completion date: December 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Dilated
• Dilated Cardiomyopathy

Intervention

Drug:
• Benazepril

• Valsartan

• Metoprolol

Locations

Country	Name	City	State
China	Xijing Hospital, Department of Cardiology	Xi'an

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	All-cause mortality		48 months after enrollment	No
Other	Cardiovascular death		48 months after enrollment	No
Other	All-cause hospital admission		48 months after enrollment	No
Other	Heart failure admission		48 months after enrollment	No
Other	changes in mitral regurgitation		12, 24 and 36 months after enrollment	No
Other	wall-motion score index	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	12, 24 and 36 months after enrollment	No
Other	Adverse events	Hypotension Hyperkalaemia Renal impairment Liver dysfunction Nonfatal stroke Angioedema	48 months after enrollment	Yes
Primary	All cause death or admission for heart failure	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.	48 months after enrollment	No
Secondary	Changes in NYHA functional class		6,12, 24 and 36 months after enrollment	No
Secondary	Left-ventricular ejection fraction	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	6,12, 24 and 36 months after enrollment	No
Secondary	Left-ventricular end-diastolic diameter		6, 12 , 24 and 36 months after enrollment	No