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 year
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; (40 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.
No Sub Projects information available for 5R01HL050424-02
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Outcomes
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