Prophylactic Lisinopril to Prevent Anthracycline Induced Left Ventricular Systolic Dysfunction (PLAID) Study.
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Change in strain rate from baseline
研究概览
简要总结
The intent of the study is to show the potential benefits of angiotensin converting enzyme inhibitors in preventing anthracycline induced cardiotoxicity.
This is a prospective, randomized, blinded and placebo-controlled clinical trial that will enroll patients who are to be treated with anthracycline chemotherapy (doxorubicin, epirubicin, idrarubicin, or mitoxantone) to either lisinopril or placebo group. The study will be performed at the Genesys Hurley Cancer Institute. The treating oncologist who intends to start the patient on anthracycline chemotherapeutic agent will provide the patient with a recruitment flyer and informed consent form and then referred to the research nurse. Subjects interested in participation, that do not meet any of the exclusion criteria, will be consented and enrolled by the research nurse prior to their first treatment with chemotherapy. Over a period of 1 to 3 weeks the study medication will be titrated in a stepwise fashion to a target of 20 mg daily, maintaining a systolic blood pressure greater than 90 mmHg. A baseline echocardiogram with strain and strain rate imaging will be obtained prior to initiation of anthracycline chemotherapy. Subsequent echocardiograms with strain and strain rate imaging will be performed every 3 months for a total of 12 months.
Patients will be followed for a total of 12 months, starting on the day of enrollment. We intend to recruit a total of 200 patients.
The primary endpoint of this study is a change in change in strain and strain rate parameters prior to, during, and after anthracycline chemotherapy compared to placebo.
Study data will be collected and managed using the Ascension installation of REDCap (Research Electronic Data Capture). REDCap is a secure, web application designed to support data capture for research studies, providing user-friendly web-based case report forms, real-time data entry validation (e.g. for data types and range checks), audit trails and a de-identified data export mechanism to common statistical packages.
Echocardiographic data will be stored in cine-loop format on a private, password protected echocardiogram viewing software and analyzed by a separate blinded cardiologist.
Patients will be evaluated according to the standard oncologic evaluation. The treating oncologist will make decisions on their treatment based on their personal standards and clinical judgement.
详细描述
To date anthracycline chemotherapy regimens still play a major role in many cancer treatments, approximately 32% of breast cancer patients, 57-70% of elderly lymphoma patients, and 50-60% of childhood cancers survivors are treated with an anthracycline regimen.
Of these patients, approximately 9-24%% of patients on anthracycline chemotherapy will develop anthracycline cardiomyopathy and the majority will present with signs and/or symptoms within the first 12 months of starting chemotherapy. The onset of anthracycline cardiomyopathy, even asymptomatic, not only negatively impacts the cardiac outcome of cancer patients, but also limits their therapeutic opportunities to less aggressive and, consequently, less effective therapies
There is limited evidence based research for treatment of anthracycline induced cardiomyopathy and is mainly targeted towards standard heart failure therapy. In 2006, Cardinale et al. found early treatment of myocardial cell injury, as defined by a rise in troponin, with enalapril prevents left ventricular ejection fraction decrease as well as the occurrence of cardiac events. Subsequently in 2010, Cardinale et al. also found that treatment of anthracycline cardiomyopathy with standard heart failure therapy (enalapril, carvedilol) at the onset of cardiomyopathy, defined as ejection fraction of ≤ 45%, lead to complete recovery of left ventricular ejection fraction and improved cardiac outcomes. Indeed, much of the research has been focused on management of patients who develop early signs of left ventricular dysfunction. Unfortunately, despite this strategy up to 11% still go on to develop New York Heart Association class 3 or 4 heart failure symptoms.
A crucial issue remains is whether or not, and eventually how, to treat patients still asymptomatic who do not yet demonstrate left ventricular dysfunction. Lisinopril use has been well studied in patients with systolic heart failure and is a class I indication in all patients with an ejection fraction of <40 %. Randomized control trials have established their benefit in reducing morbidity and mortality in heart failure with reduced ejection fraction. Since anthracycline induced-cardiotoxicity has a significant impact on overall prognosis in cancer patients and despite treatment after the development of left ventricular dysfunction from anthracyclines will still result in a large amount of the patient population developing heart failure, there is an urgent need in prophylactic treatment in preventing anthracycline-induced left ventricular dysfunction.
Thus, the intent of our study is to show the potential benefits of angiotensin converting enzyme inhibitors in preventing anthracycline induced cardiotoxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Care Provider)
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
- •Diagnosed with a type of cancer and intended to be on an anthracycline chemotherapy regimen by treating oncologist.
排除标准
- •Inability or unwillingness to give informed consent
- •Subjects with a contraindication to angiotensin converting enzyme inhibitors such as history of angioedema or hypersensitivity related to previous treatment with an angiotensin converting enzyme inhibitor
- •Subjects with a history of hereditary or idiopathic angioedema
- •Subjects currently taking aliskiren (major drug interaction-)
- •Subjects currently taking a neprilysin inhibitor (e.g. sacubitril or entresto)
- •Subjects already on treatment with angiotensin converting enzyme inhibitors, or taking lithium
- •Renal insufficiency defined as creatinine clearance <30
- •Women <50 who capable of child bearing who have not had surgical contraception such as hysterectomy or tubal ligation
- •Oncologic life expectancy shorter than 12 months
- •Systolic blood pressure <90 mmHg prior to enrollment
研究组 & 干预措施
Lisinopril treatment
These patients will be initiated at 5mg lisinopril daily by the research nurse at the time of enrollment. The drug will then be titrated up by the research nurse in a stepwise fashion from 5mg, to 10mg, and then to 20mg once a day every 1 to 3 weeks according to their regular/scheduled next office visits. Blood pressure will be monitored at every visit by the research nurse if it is less than or equal to 90 mmHg
干预措施: Lisinopril (Drug)
Placebo Oral Tablet
These patients will be started on the placebo medication at the time of enrollment. According to their regular scheduled visits every 1 to 3 weeks, they will meet with the research nurse and be given a new placebo medication to take once a day.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Change in strain rate from baseline
时间窗: 12 months from enrollment
The primary outcome is a change in strain and strain rate from baseline echocardiogram
次要结局
- Heart failure and left ventricular dysfunction(12 months from enrollment)
研究者
Jackie Kirchen
Cardiology Fellow
Ascension Health