Awardee OrganizationCHILDREN'S HOSP OF PHILADELPHIA
Description
Abstract Text
The primary aim of this project is to determine whether the chronic
administration of enalapril, an inhibitor of angiotensin converting enzyme
(ACE), will reduce the progression of cardiac dysfunction in pediatric
oncology patients who have received anthracyclines, and who are not
currently on digoxin, diuretics or vasodilators for congestive heart
failure (CHF). The project will include a randomized, double blind trial
of enalapril versus placebo in approximately 168 patients at least 2 years
off treatment with some cardiac dysfunction (without CHF) after receiving
anthracyclines. Randomization will be stratified by total anthracycline
dose, follow-up time from treatment, and age at time of treatment. We
define cardiac dysfunction to include a fall in left ventricular
shortening fraction (LVSF) as measured by echocardiogram, a moderate or
severe abnormality on maximal cardiac index as measured on cycle ergometry
testing, an abnormal LV ejection fraction (LVEF) by gated nuclear
angiography, a prolonged QTc on ECG, or a history of exercise intolerance.
All patients will receive the following baseline tests: (1) Maximal
Cardiac Index (MCI) on cycle ergometry; (2) Echocardiogram/Doppler
determined left ventricular end systolic wall stress (ESWS); (3) gated
nuclear angiography (GNA) to determine left ventricular ejection fraction;
(4) Holter monitor for 24 hour ECG monitoring. Patients will be randomized
to either enalapril or placebo. Follow-up visits to ensure compliance and
screen for side effects will be conducted. MCI and ESWS stress will be
measured twice yearly, while all 4 tests will be repeated at the
conclusion of the trial, after 4 to 5 years of treatment. The primary
outcome variables will be the rate of decline in MCI and the rate of
increase in ESWS. Secondary outcomes will be the change in LVEF and the
incidence of arrhythmias.
The second aim is to develop an algorithm to determine indications for
enalapril use should we succeed in showing a treatment effect. This will
require 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.
We have enrolled 91 patients at present.
No Sub Projects information available for 5M01RR000240-35 0415
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