ENALAPRIL AFTER ANTHRACYCLINE CARDIOTOXICITY

蒽环类药物心脏毒性后依那普利

• 批准号: 6219793
• 负责人: JEFFREY H SILBER
• 金额: $ 0.06万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219793
• 关键词: anthracyclines; cancer complication; cardiotoxin; cardiovascular disorder prevention; child (0-11); clinical research; clinical trials; drug adverse effect; enalapril; health care model; heart disorder; heart disorder chemotherapy; human subject; human therapy evaluation; mathematical model; model design /development; pediatric neoplasm /cancer; anthracyclines; cancer complication; cardiotoxin; cardiovascular disorder prevention; child (0-11); clinical research; clinical trials; drug adverse effect; enalapril; health care model; heart disorder; heart disorder chemotherapy; human subject; human therapy evaluation; mathematical model; model design /development; pediatric neoplasm /cancer

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.

该项目的主要目的是确定依那普利长期给药是一种血管紧张素转化酶（ACE）的抑制剂，是否会减少患儿科肿瘤学患者心脏功能障碍的进展，而这些患者曾接受过蒽环类药物，并且没有目前接受过毒素，利尿剂或vasodilators for Concodiver for Concsive Heartdafor（CHFFF）。 该项目将在接受蒽环类药物后，在大约168名患者中，包括168例至少两年的心脏功能障碍（无CHF），在168例患者中进行了一项随机的双盲试验。 随机分组将按全蒽环类剂量，治疗的随访时间以及治疗时的年龄进行分层。 我们将心脏功能障碍定义为包括通过超声心动图测量的左心室缩短分数（LVSF）的下降，这是对最大心脏指数的中等或严重异常，如周期的循环测试测试，在循环的LV弹性分数（LVEF（LVEF）中，通过gated核核管静态静电量均进行了ECG，在循环的LV弹性分数（LVEF）上进行了ECG型均可进行的ECG型量。所有患者将接受以下基线测试：（1）循环测量法上最大心脏指数（MCI）； （2）超声心动图/多普勒确定的左心室末端收缩压壁应力（ESWS）； （3）门控核血管造影（GNA）确定左心室射血分数； （4）24小时的Holter Monitor进行ECG监控。 患者将被随机分为依那普利或安慰剂。 后续访问以确保将进行遵守和筛查副作用。 MCI和ESWS应力将每年两次测量，而在经过4至5年的治疗后，将在试验结束时重复所有4个测试。 主要结果变量将是MCI的下降率和ESW的增加率。 次要结果将是LVEF的变化和心律不齐的发生率。第二个目的是开发一种算法，以确定依那普利使用的适应症，如果我们成功表现出治疗效果。 这将需要对患者特征，治疗类型，治疗和随访期间的心脏状况以及成本效益和医疗决策模型测试所提出算法的模型的发展，对心脏功能障碍的可能性进行建模。