Pharmacologic Therapies to Mitigate Radiation- Associated Heart Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 2
- 主要终点
- Percent difference in the radiation (RT)-induced reduction of myocardial perfusion
研究概览
简要总结
Radiation therapy is an essential treatment for tumors in the chest area, including breast, lung, esophageal, mediastinal cancers, and spine metastases. Although technical advances have reduced treatment-related illness and death, radiation exposure to the heart can still cause substantial rates of radiation-induced heart disease (RIHD) among survivors.
For example, about 21% of non-small cell lung cancer patients receiving a mean heart dose of 20 Gy or higher experience major adverse cardiac events (MACE) within 2 years. In breast cancer patients, the risk of MACE increases by about 7% for each additional Gy of mean heart dose.
There is currently no established medication strategy to prevent or reduce RIHD.
Preclinical and clinical studies show that statins and angiotensin-converting enzyme (ACE) inhibitors may help reduce radiation-induced heart disease (RIHD). Statins and ACE inhibitors are generally well tolerated, available as generic drugs, and commonly used to help prevent cardiovascular disease. They may protect the heart by reducing damage to blood vessel lining (endothelial damage), microvascular dysfunction, atherosclerosis, reduced blood flow (ischemia), and fibrosis (scarring).
This study is a prospective, randomized, placebo-controlled phase II hybrid decentralized trial. Patients receiving standard radiation therapy and expected to receive an equivalent dose of at least 25 Gy (EQD2) to at least 10% of the heart will be randomly assigned to receive either:
- placebo, or
- Atorvastatin 20 mg plus Lisinopril 5 mg daily. The medications will be taken during radiation therapy and continued for 6 months after treatment.
The study aims to determine whether the intervention can reduce radiation-related decreases in blood flow to the heart, measured using myocardial perfusion imaging, such as positron emission tomography (PET), which is commonly used to evaluate the risk of coronary heart disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent obtained to participate in the study and HIPAA
- •authorization for release of personal health information.
- •Subjects is willing and able to comply with study procedures based on the
- •judgement of the investigator.
- •Consent for serial blood draws and consent for use of biological specimens.
- •Age ≥ 18 years at the time of consent
排除标准
- •Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- •Pre-existing use of a statin or ACE-inhibitor
- •Pre-existing hypotension
研究组 & 干预措施
statins and angiotensin-converting enzyme (ACE) inhibitors
Patients expected to receive ≥25 Gy equivalent dose in 2 Gy fractions (EQD2) to at least 10% of the heart will be treated with statins and angiotensin-converting enzyme (ACE) inhibitors.
干预措施: Atorvastatin and Lisinopril (Drug)
Placebo
Patients expected to receive ≥25 Gy equivalent dose in 2 Gy fractions (EQD2) to at least 10% of the heart will take inhibitors.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent difference in the radiation (RT)-induced reduction of myocardial perfusion
时间窗: Pre radiation therapy and 6-month post radiation therapy
Percent difference in the radiation (RT)-induced reduction of myocardial perfusion in cardiac regions receiving ≥25Gy equivalent dose in 2Gy fractions (EQD2) based on comparison of before and after RT among participants receiving placebo and statins and angiotensin-converting enzyme (ACE) inhibitors intervention.
次要结局
- Percent Change in Radiation-Induced Myocardial Perfusion Reduction by Cardiac Dose: Placebo vs Statin and ACE Inhibitor Therapy(Pre radiation therapy and 6-month post radiation therapy)
- Change in for cardiac biomarker panel(Pre radiation therapy and 3 months and 6-month post radiation therapy)
- Correlation between cardiac stress and perfusion biomarkers and radiation dose(Pre radiation therapy and 3 months and 6-month post radiation therapy)
- Rates of major adverse cardiac events(At follow-up of 1, 2, and 3 years.)