STOP-CA: Statins to prevent Cardiotoxicity from Anthracyclines

STOP-CA：他汀类药物可预防蒽环类药物的心脏毒性

• 批准号: 9176736
• 负责人: Tomas G Neilan
• 金额: $ 65.36万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9176736
• 关键词: Acute; Admission activity; Animals; Anthracyclines; Attenuated; Biological; Biological Markers; Blinded; Breast; Cardiac; Cardiac Death; Cardiotoxicity; Cell Death; Chemotherapy-Oncologic Procedure; Cholesterol; Clinical; Clinical Data; Clinical Research; Clinical Trials; Congestive Heart Failure; Consensus; Controlled Clinical Trials; Data; Development; Drug usage; Early Diagnosis; Early identification; Echocardiography; Event; Fibrosis; Functional disorder; Goals; Gold; Heart; Heart failure; Hematologic Neoplasms; Hospitalization; Image; Imaging Techniques; Incidence; Injury; Laboratories; Lead; Left Ventricular Ejection Fraction; Magnetic Resonance; Magnetic Resonance Imaging; Malignant Neoplasms; Measurement; Measures; Mus; Myocardial; Newly Diagnosed; Non-Hodgkin' s Lymphoma; Participant; Patients; Pharmaceutical Preparations; Placebo Control; Placebos; Plasma; Protocols documentation; Randomized; Reader; Recruitment Activity; Risk Factors; Role; Safety; Testing; Tissues; Troponin; Work; abstracting; animal data; arm; atorvastatin; base; chemotherapy; coronary fibrosis; double-blind placebo controlled trial; extracellular; high risk; improved; indexing; mortality; oncology; outcome forecast; prevent; protective effect; standard care

7. Project Summary/Abstract Survival among patients with non-Hodgkin's Lymphoma (NHL) has improved due to a combination of earlier diagnosis, improved characterization and better treatments. Anthracyclines are an integral part of most standard chemotherapy regimens for patients with NHL and have contributed to this improved survival. However, the use of anthracyclines is limited by the well recognized and frequent occurrence of cardiotoxicity, that manifests itself as a reduction in left ventricular ejection fraction (LVEF) leading to congestive heart failure. In comparison to other patients receiving anthracycline-based chemotherapy, patients with NHL are at the highest risk of congestive heart failure. In animal studies, statins reduced myocardial fibrosis and cell death after anthracyclines and in small clinical studies statins preserved LVEF. Therefore, in this randomized multi- center placebo-controlled clinical trial, Statins TO Prevent the Cardiotoxicity from Anthracyclines (STOP-CA), we will determine whether statins preserve LVEF 12 months after the initiation of chemotherapy in 270 patients with NHL undergoing anthracycline-based chemotherapy. We will test the effect of statin therapy on cardiac magnetic resonance (CMR)-derived LVEF as CMR-derived LVEF is the gold-standard for non-invasive measurement of LVEF. All measurements will be performed in a core imaging laboratory by expert reviewers blinded to all other data using a standardized protocol. This study is not powered to detect a difference in clinical events; however, as statin therapy has been shown retrospectively to reduce heart failure hospitalizations, and this will be a key goal of subsequent studies, we will capture this data. We also propose to use the additive tissue characterization available with CMR imaging to test the effect of statin therapy on anthracycline-induced myocardial fibrosis and whether fibrosis predicts the decrease in LVEF. Finally, we will use myocardial strain (a sensitive index of cardiac function) measured using echocardiography and plasma levels of troponin (reflecting myocardial injury), both widely available and scalable parameters, to identify early during treatment NHL patients at high risk of LVEF decline and to test whether statin therapy has beneficial effects on myocardial injury and early LV dysfunction. At the completion of this proposal, we will have characterized the effect of statins on anthracycline-induced LV dysfunction in patients with NHL, established their safety and identified patients with NHL at high risk of cardiotoxicity.

7. 项目总结/摘要 由于早期的联合治疗，非霍奇金淋巴瘤 (NHL) 患者的生存率有所提高 诊断、改进表征和更好的治疗。蒽环类药物是大多数药物的组成部分 NHL 患者的标准化疗方案有助于提高生存率。 然而，蒽环类药物的使用受到众所周知且频繁发生的心脏毒性的限制， 表现为左心室射血分数（LVEF）降低，导致充血性心力衰竭。 与其他接受蒽环类化疗的患者相比，NHL 患者处于 充血性心力衰竭的风险最高。在动物研究中，他汀类药物可减少心肌纤维化和细胞死亡 在使用蒽环类药物和小型临床研究中，他汀类药物可以保留 LVEF。因此，在这个随机多 中心安慰剂对照临床试验，他汀类药物预防蒽环类药物的心脏毒性 (STOP-CA)， 我们将在 270 名患者开始化疗后 12 个月确定他汀类药物是否能保持 LVEF 患有接受蒽环类化疗的 NHL。我们将测试他汀类药物治疗对心脏的影响 磁共振 (CMR) 衍生的 LVEF 因为 CMR 衍生的 LVEF 是无创性治疗的黄金标准 左心室射血分数 (LVEF) 的测量。所有测量将由专家评审员在核心成像实验室进行 使用标准化协议对所有其他数据不知情。这项研究并不能检测差异 临床事件；然而，由于他汀类药物治疗已被回顾性地证明可以减少心力衰竭 住院治疗，这将是后续研究的一个关键目标，我们将捕获这些数据。我们还建议 使用 CMR 成像提供的附加组织特征来测试他汀类药物治疗的效果 蒽环类药物诱导的心肌纤维化以及纤维化是否预示着 LVEF 的降低。最后，我们将 使用超声心动图和血浆测量的心肌应变（心功能的敏感指标） 肌钙蛋白水平（反映心肌损伤），广泛可用和可扩展的参数，以识别早期 治疗期间 LVEF 下降高风险的 NHL 患者，并测试他汀类药物治疗是否有益 对心肌损伤和早期左室功能障碍的影响。完成本提案后，我们将 表征了他汀类药物对 NHL 患者蒽环类药物引起的左心室功能障碍的影响，建立 其安全性并确定了患有心脏毒性高风险的 NHL 患者。