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Long Term Effects of Enalapril and Losartan on Genetic Heart Disease
This study has been completed.
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)
Information provided by: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00001534
  Purpose

The human heart is divided into four chambers. One of the four chambers, the left ventricle, is the chamber mainly responsible for pumping blood out of the heart into circulation. Hypertrophic cardiomyopathy (HCM) is a genetically inherited disease causing an abnormal thickening of the heart muscle, especially the muscle making up the left ventricle. When the left ventricle becomes abnormally large it is called left ventricular hypertrophy (LVH). This condition can cause symptoms of chest pain, shortness of breath, fatigue, and heart beat palpitations.

This study is designed to compare the ability of two drugs (enalapril and losartan) to improve symptoms and heart function of patients diagnosed with hypertrophic cardiomyopathy (HCM).

Researchers have decided to compare these drugs because each one has been used to treat patients with other diseases causing thickening of the heart muscle. In these other conditions, enalapril and losartan have improved symptoms, decreased the thickness of heart muscle, improved blood flow and supply to the heart muscle, and improved the pumping action of the heart muscle.

In this study researchers will compare the effectiveness of enalapril and losartan when given separately and together to patients with hypertrophic cardiomyopathy (HCM).


Condition Intervention
Hypertrophic Cardiomyopathy
Left Ventricular Hypertrophy
Myocardial Ischemia
Drug: Losartan

MedlinePlus related topics: Cardiomyopathy Heart Diseases
Drug Information available for: Losartan Losartan potassium Enalapril Enalapril maleate Enalaprilat Angiotensin II Angiotensin II, ile(5)-
U.S. FDA Resources
Study Type: Observational
Official Title: Double-Blind, Placebo-Controlled Study of the Long Term Effects of Angiotensin Converting Enzyme Inhibition (Enalapril) and Angiotensin II Receptor Blockade (Losartan) on Genetically-Induced Left Ventricular Hypertrophy in Non-Obstructive HCM

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 112
Study Start Date: September 1996
Estimated Study Completion Date: April 2003
Detailed Description:

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by left ventricular (LV) hypertrophy. There is often associated LV diastolic dysfunction and myocardial ischemia. The severity of the LV hypertrophy, diastolic dysfunction, and myocardial ischemia are important determinants of clinical outcomes. Angiotensin II modulates cell growth and cardiac function. There is also increasing evidence that the renin-angiotensin system (RAS) may be present in cardiac cells, and the hypertrophic action of angiotensin II could therefore be mediated by circulating or locally produced hormone. Animal and clinical studies have demonstrated that independent of their effects on systemic blood pressure, ACE inhibition and angiotensin II receptor (AT1) blockade can reduce cardiac hypertrophy, improve LV diastolic function and myocardial ischemia. AT1 blockade may be preferable to ACE inhibitors because by inhibiting angiotensin II from binding to its receptor, the system can be turned off irrespective of the source of angiotensin II. Also, there may be fewer side effects due to lack of bradykinin. This is a double-blind, placebo-controlled study that examines the abilities of enalapril (ACE inhibition) and losartan (AT1 blockade), separately or in combination, to cause regression of the cardiac hypertrophy, and to improve LV function and myocardial perfusion in non-obstructive HCM.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

HCM of either gender, aged 20-55 years.

Non-dilated LV (LVIDd less than 60 mm) with LV wall thickness of greater than or equal to 16 mm measured in any LV segment by NMR.

Non-obstructive HCM: A LV outflow gradient of less than or equal to 30 mm Hg gradient at rest and less than or equal to 55 mm Hg following isoproterenol infusion to a heart rate of greater than or equal to 120 beats per minute at cardiac catheterization.

New York Heart Association functional class I-III.

Patients who have participated in the previous toxicity study may be recruited for this study, if they wish.

Patients who have previously taken an ACE inhibitor or losartan could only be included in this study, if they have been off these drugs for a period of 6 months or longer.

EXCLUSION CRITERIA

Severe cardiac symptoms at rest (NYHA IV).

LV outflow tract gradient of greater than 30 mm Hg at rest or greater than 55 mm Hg following isoproterenol infusion to a heart rate of greater than or equal to 120 beats per minute at cardiac catheterization.

Systemic diseases (respiratory, neurologic, or locomotor) that prevent exercise testing, echocardiography or NMR, MUGA, thallium studies, and cardiac catheterization.

Coronary artery disease (greater than 50% arterial luminal narrowing of a major epicardial vessel) or congenital cardiovascular abnormalities (e.g. ASD, VSD, coronary anomalies).

Chronic atrial fibrillation.

Bleeding disorder (PTT greater than 35 sec, pro time greater than 14.7 sec, platelet count less than 154 k/mm3).

Anemia (Hb less than 12.7 g/dl in males and less than 11.0 g/dl in females); renal impairment (BUN greater than 22 mg/dl and serum creatinine greater than 1.4 mg/dl); K+ less than 3.3 mmol/l or greater than 5.1 mmol/l.

Hypertension: basal systolic and diastolic pressures of greater than 160 mm Hg or greater than 95 mm Hg, respectively on two occasions separated by one hour of rest.

Hypotension: basal sitting systolic arterial pressure less than 100 mm Hg confirmed 30 minutes later.

Must have ability to estimate LV wall thickness.

Radiographic evidence of overt cardiac failure (pulmonary edema on chest X-ray).

Negative urine pregnancy test.

Pregnant or lactating female patients.

Diminished LV systolic function (resting or exercise LV ejection fractions estimated by radionuclide angiography less than 50%).

Dependence on other cardioactive drugs such as diuretics, verapamil, B-blockers, or antiarrhythmic drugs to control symptoms and arrhythmias.

Negative HIV test.

Sensitivity to ACE inhibitor e.g. angioedema.

Must have ability to set up an outpatient monitoring system.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001534

Locations
United States, Maryland
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
Study ID Numbers: 960144, 96-H-0144
Study First Received: November 3, 1999
Last Updated: March 3, 2008
ClinicalTrials.gov Identifier: NCT00001534  
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Genetics
Myocardial Ischemia
Diastolic Dysfunction
Renin-Angiotensin System
Hypertrophic Cardiomyopathy
Left Ventricular (LV) Hypertrophy

Study placed in the following topic categories:
Pathological Conditions, Anatomical
Hypertrophy, Left Ventricular
Losartan
Heart Diseases
Myocardial Ischemia
Vascular Diseases
Constriction, Pathologic
Aortic valve stenosis
Ischemia
Angiotensin II
Cardiomyopathies
Heart Valve Diseases
Enalapril
Hypertrophy
Enalaprilat
Cardiomyopathy, Hypertrophic
Aortic Valve Stenosis
Cardiomegaly

Additional relevant MeSH terms:
Angiotensin II Type 1 Receptor Blockers
Pathologic Processes
Aortic Stenosis, Subvalvular
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Cardiovascular Diseases
Cardiovascular Agents
Anti-Arrhythmia Agents
Antihypertensive Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009