ENALAPRIL AFTER ANTHRACYCLINE CARDIOTOXICITY

蒽环类药物心脏毒性后依那普利

• 批准号: 6116856
• 负责人: JEFFREY H SILBER
• 金额: $ 2.47万
• 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/6116856
• 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. We have enrolled 91 patients at present.

该项目的主要目的是确定慢性 依那普利的给药，一种转化酶的血管紧张素抑制剂 （ACE），将减少小儿心脏功能障碍的进展 接受过邻苯式的肿瘤学患者，但没有 目前使用的地高辛，利尿剂或血管扩张剂用于充血性心脏 失败（CHF）。该项目将包括一个随机的双盲试用 在大约168名患者中，依那普利与安慰剂至少2年 接受一些心脏功能障碍（无瑞士法郎）的治疗后接受治疗 蒽环类动物。 随机化将按总蒽环类分层 剂量，治疗的随访时间以及治疗时的年龄。我们 定义心脏功能障碍以包括左心室掉落 通过超声心动图，中等或中等或 在循环基因测定法上测量的最大心脏指数的严重异常 测试，通过门控核的异常LV射血分数（LVEF） 血管造影，延长心电图或运动不宽容史。 所有患者将接受以下基线测试：（1）最大 心脏指数（MCI）在循环基因测定法上； （2）超声心动图/多普勒 确定的左心室收缩压壁应力（ESW）； （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 要么为依纳普利或安慰剂。 后续访问以确保合规性和 将进行副作用的屏幕。 MCI和ESWS压力将是 每年测量两次，而所有4个测试将在 经过4至5年的治疗后，试验的结论。 主要 结果变量将是MCI的下降率和 ESW的增加。 次要结果将是LVEF和 心律不齐的发生率。 第二个目的是开发算法以确定 依那普利的使用应成功显示出治疗效果。这会 需要对患者进行心脏功能障碍的概率进行建模 治疗中的特征，治疗类型，心脏状况 治疗和随访以及成本效益的发展和 医疗决策模型测试拟议算法。 目前，我们已经招募了91名患者。