Trial record 8 of 94 for:    "DMD-associated dilated cardiomyopathy" OR "Cardiomyopathy, Dilated"

High Dose RAS Inhibitor for Dilated Cardiomyopathy

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hezheng, Xijing Hospital
ClinicalTrials.gov Identifier:
NCT01917149
First received: July 30, 2013
Last updated: August 3, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Dilated Cardiomyopathy
Drug: Benazepril
Drug: Valsartan
Drug: Standard medicaiton without ACEI or ARB
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Xijing Hospital:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Other Outcome Measures:
  • 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


Estimated Enrollment: 600
Study Start Date: March 2004
Estimated Study Completion Date: December 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of dilated cardiomyopathy
  • Left ventricular ejection fraction < 35% within 6 months prior to study entry
  • NYHA Functional classes of III-IV
  • Stable condition at least 6 months before enrollment on conventional therapy.

Exclusion Criteria:

  • Contraindication for treatment with ACEI or ARB such as allergy and angioedema, and with β-blockers such as asthma and atrioventricular block of II-III degree
  • Acute myocardial infarction or unstable angina within 30 days before randomization
  • Scheduled or performed heart transplantation or cardiomyoplasty
  • Acute or subacute stage of myocarditis
  • Acute heart failure with pulmonary edema and hypoperfusion
  • Pregnancy or lactation
  • Primary valve disease
  • Excessive use of alcohol or illicit drugs
  • Renal artery stenosis >50%
  • Impaired renal function: estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2
  • Impaired liver function: total bilirubin greater than 2 times upper limit of normal, serum aspartate AST or alanine ALT greater than 3 times the upper limit of normal
  • Hemoglobin less than 8 mg/dl
  • Hyperkalaemia (serum potassium >5.5mmol/l)
  • Any co-morbidity with impact on survival
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01917149

Locations
China
Xijing Hospital, Department of Cardiology
Xi'an, China, 710032
Sponsors and Collaborators
Xijing Hospital
Investigators
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
  More Information

No publications provided

Responsible Party: Hezheng, Professor, Xijing Hospital
ClinicalTrials.gov Identifier: NCT01917149     History of Changes
Other Study ID Numbers: SIRAAS-DC
Study First Received: July 30, 2013
Last Updated: August 3, 2013
Health Authority: China: Ethics Committee

Keywords provided by Xijing Hospital:
Dilated cardiomyopathy
High dose ACEI/ARB

Additional relevant MeSH terms:
Cardiomyopathy, Dilated
Cardiomyopathies
Cardiomegaly
Heart Diseases
Cardiovascular Diseases
Angiotensin-Converting Enzyme Inhibitors
Benazepril
Valsartan
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on April 20, 2014