Trial record 8 of 98 for:    "DMD-associated dilated cardiomyopathy" OR "Cardiomyopathy, Dilated"

Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hezheng, Xijing Hospital
ClinicalTrials.gov Identifier:
NCT01917149
First received: July 30, 2013
Last updated: May 16, 2014
Last verified: May 2014
  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 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 Intervention Phase
Dilated Cardiomyopathy
Drug: Benazepril
Drug: Valsartan
Drug: Metoprolol
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 Supramaximal Titrated Inhibition of RAAS in Idiopathic 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


Enrollment: 480
Study Start Date: March 2005
Study Completion Date: December 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Metoprolol
Experimental: Low-dose valsartan
Patients randomized to low dose valsartan receive valsartan 80 mg until study completion.
Drug: Valsartan
Experimental: Low dose Benazepril
Patients randomized to low dose Benazepril receive Benazepril 10 mg until study completion.
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.
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.
Drug: Benazepril

  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%
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: May 16, 2014
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
Metoprolol
Benazepril
Valsartan
Metoprolol succinate
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on August 18, 2014