Clinical trial NCT00000547: Enalapril After Anthracycline Cardiotoxicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Diseases
Heart Diseases
Heart Failure
Myocardial Diseases
Lead sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Sponsor class: NIH
First posted: 1999-10-28
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief 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.

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.

The study completion date listed in this record was obtained from the "Completed Date" entered in the Query View Report System (QVR).

Eligibility 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Jeffrey Silber
References:
citation: 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. doi: 10.1067/mhj.2001.118115.