Enalapril After Anthracycline Cardiotoxicity
Information source: National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cardiovascular Diseases; Heart Diseases; Heart Failure; Myocardial Diseases
Intervention: enalapril (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Heart, Lung, and Blood Institute (NHLBI) Official(s) and/or principal investigator(s): Jeffrey Silber, Affiliation: Children's Hospital of Philadelphia
Summary
To determine if the chronic administration of enalapril, an inhibitor of angiotensin
converting enzyme (ACE), reduces progression of cardiac dysfunction in pediatric oncology
patients who have received anthracyclines, and who are not currently on digoxin, diuretics,
or vasodilators for heart failure.
Clinical Details
Study design: Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment
Detailed description:
BACKGROUND:
Pediatric oncology patients who have been treated with anthracycline therapy as a part of
their chemotherapeutic regimen often subsequently develop left ventricular failure. The
optimal medical management is not known. This trial will be the first to provide
comprehensive data on a well characterized population regarding the role of afterload
reduction using enalapril to treat ventricular dysfunction after anthracycline chemotherapy
DESIGN NARRATIVE:
Randomized, double-blind. Randomization was stratified by total anthracycline dose,
follow-up time from treatment, and age at time of treatment. All patients received the
following baseline tests: Maximal Cardiac Index (MCI) on cycle ergometry;
echocardiogram/Doppler determined left ventricular end systolic wall stress (ESWS); gated
nuclear angiography (GNA) to determine left ventricular ejection fraction; Holter monitoring
for 24 hour ECG monitoring. Patients were randomized to either enalapril or placebo.
Follow-up visits were conducted to ensure compliance and screen for side effects. MCI and
ESWS were measured twice yearly, while all four tests were repeated at the conclusion of the
trial, after four to five years of treatment. The primary outcome variables were the rate
of decline in MCI and the rate of increase in ESWS. Secondary outcomes were the change in
left ventricular ejection fraction and the incidence of arrhythmias. A second aim of the
study was to develop an algorithm to determine indications for enalapril use if the study
succeeded in showing a treatment effect. This required modeling the probability of cardiac
dysfunction given patient characteristics at treatment, treatment type, cardiac status
during treatment and at follow-up, and the development of cost effectiveness and medical
decision making models testing the proposed algorithm.
Eligibility
Minimum age: 1 Year.
Maximum age: 17 Years.
Gender(s): Both.
Criteria:
Boy and girl pediatric oncology patients, at least two years off treatment, with some
cardiac dysfunction, but not congestive heart failure, after receiving anthracyclines.
Patients were not on digoxin, diuretics, or vasodilators for heart failure.
Locations and Contacts
Additional Information
Related publications: Silber JH, Cnaan A, Clark BJ, Paridon SM, Chin AJ, Rychik J, Hogarty AN, Cohen MI, Barber G, Rutkowsky M, Kimball TR, Delaat C, Steinherz LJ, Zhao H, Tartaglione MR. Design and baseline characteristics for the ACE Inhibitor After Anthracycline (AAA) study of cardiac dysfunction in long-term pediatric cancer survivors. Am Heart J. 2001 Oct;142(4):577-85.
Starting date: April 1994
Last updated: January 3, 2006
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