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Trial record 7 of 163 for:    Idiopathic Dilated Cardiomyopathy

Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy

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ClinicalTrials.gov Identifier: NCT01917149
Recruitment Status : Completed
First Posted : August 6, 2013
Last Update Posted : May 19, 2014
Sponsor:
Information provided by (Responsible Party):
Hezheng, Xijing Hospital

Tracking Information
First Submitted Date  ICMJE July 30, 2013
First Posted Date  ICMJE August 6, 2013
Last Update Posted Date May 19, 2014
Study Start Date  ICMJE March 2005
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 3, 2013)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01917149 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 3, 2013)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 3, 2013)
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
Official Title  ICMJE 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Dilated Cardiomyopathy
Intervention  ICMJE
  • Drug: Benazepril
  • Drug: Valsartan
  • Drug: Metoprolol
Study Arms  ICMJE
  • Experimental: Metoprolol
    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.
    Intervention: Drug: Metoprolol
  • Experimental: Low-dose valsartan
    Patients randomized to low dose valsartan receive valsartan 80 mg until study completion.
    Intervention: Drug: Valsartan
  • Experimental: Low dose Benazepril
    Patients randomized to low dose Benazepril receive Benazepril 10 mg until study completion.
    Intervention: Drug: Benazepril
  • 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.
    Intervention: Drug: Valsartan
  • 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.
    Intervention: Drug: Benazepril
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 16, 2014)
480
Original Estimated Enrollment  ICMJE
 (submitted: August 3, 2013)
600
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01917149
Other Study ID Numbers  ICMJE SIRAAS-DC
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hezheng, Xijing Hospital
Study Sponsor  ICMJE Xijing Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Xijing Hospital
Verification Date May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP