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。项目摘要/摘要 由于早期的组合，非霍奇金淋巴瘤（NHL）患者的生存率有所提高 诊断，改进的表征和更好的治疗方法。蒽环类药物是大多数不可或缺的一部分 NHL患者的标准化学疗法方案，并有助于提高生存率。 但是，蒽环类药物的使用受到众所周知且频繁出现的心脏毒性的限制， 这表现为减少左心室射血分数（LVEF）的减少，导致充血性心力衰竭。 与接受基于蒽环类化疗的其他患者相比，NHL患者处于 充血性心力衰竭的最高风险。在动物研究中，他汀类药物减少了心肌纤维化和细胞死亡 在邻苯二甲酸酯和小型临床研究中，他汀类药物保留了LVEF。因此，在这个随机多的 中心安慰剂对照临床试验，他汀类药物，以防止心脏毒性来自蒽环类药物（Stop-Ca）， 我们将确定他汀类药物在270名患者开始化疗后12个月是否保留LVEF NHL接受基于蒽环类药物的化学疗法。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作为CMR衍生的LVEF是非侵入性的金标准 LVEF的测量。所有测量将由专家审阅者在核心成像实验室中进行 使用标准化协议对所有其他数据视而不见。这项研究没有能力检测 临床事件；但是，由于他汀类药物疗法已被追溯显示以减少心力衰竭 住院治疗，这将是随后研究的关键目标，我们将捕获此数据。我们也建议 使用CMR成像可用的添加性组织表征来测试他汀类药物治疗对 蒽环类诱导的心肌纤维化以及纤维化是否预测LVEF的减少。最后，我们会的 使用使用超声心动图和等离子体测量的心肌菌株（心脏功能的敏感索引） 肌钙蛋白的水平（反映心肌损伤），既可以识别 在治疗期间，NHL患者的LVEF高风险下降，并测试他汀类药物治疗是否有益 对心肌损伤和早期LV功能障碍的影响。该提案完成后，我们将 汀类药物对NHL患者的蒽环类药物诱导的LV功能障碍的影响（已建立） 他们的安全性并确定患有心脏毒性高风险的NHL患者。