REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 608
- 试验地点
- 40
- 主要终点
- Rate of anthracycline-induced cardiotoxicity events
研究概览
简要总结
Multinational, prospective, proof of concept phase II, double-blinded, sham-controlled, randomized clinical trial (RCT) to evaluate the efficacy and safety of Remote Ischaemic PreConditioning (RIPC) in Lymphoma patients receiving anthracyclines.
详细描述
Multinational, prospective, proof of concept phase II, double-blinded, sham-controlled, randomized clinical trial (RCT) to evaluate the efficacy and safety of Remote Ischaemic PreConditioning (RIPC) in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles will be eligible. Patients fulfilling all inclusion and no exclusion criteria will be enrolled and undergo baseline Cardiac Magnetic Baseline (CMR), and high sensitivity troponin (hsTn) and NT-proBNP blood test. Patients with confirmed LVEF >40% by CMR will be randomized 1:1 to RIPC vs simulated RIPC (Sham). After the third chemotherapy cycle, a second CMR+ hsTn/ NT-proBNP will be performed for the validation of the early marker of cardiotoxicity. A third hsTn/ NT-proBNP blood test will be performed in the last chemotherapy cycle. Nine weeks after finishing chemotherapy, a last CMR+ hsTn/ NT-proBNP will be performed. Patients will be followed-up for clinical events at 6, 12, 18, 30 and 42 months until the last patient undergoes the final CMR. When the last patient undergoes the third CMR, the follow-up will be closed. The median follow-up estimation for clinical endpoints is 36 months (range: 6 to 60 months).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥18 years old NHL, HL or breast cancer diagnosis Scheduled to undergo chemotherapy including ≥ 240 mg/k2 cumulative dose of anthracyclines.
- •Pre-chemo LVEF >40% on screening echocardiography.
- •Presence of ≥1 of the following risk factors for developing cardiotoxicity:
- •Previous coronary artery disease (any of the following):
- •Previous coronary revascularisation (PCI or CABG) or Medical history of previous significant nonrevascularized coronary stenosis Previous Acute Coronary Syndrome / Acute Myocardial Infarction with a LVEF > 40 LVEF 41-54% Age ≥ 65 years old Previous diagnosis of arterial hypertension (with or without treatment) Chronic kidney disease (estimated glomerular filtration rate <60ml/min/1.73m2) Current or former smoker. Obesity (BMI≥30 kg/m2) LVH on screening echocardiography (LV thickness ≥12mm). High alcohol intake (≥21 alcoholic beverages per week) Sinus rhythm on screening ECG Previous diagnosis of diabetes (except those treated with sulfonylureas or those with neuropathy) Previous non-anthracycline-based chemotherapy Signed Informed Consent Form (ICF)
排除标准
- •History of any of the following diseases:
- •Any cancer who received anthracyclines treatment before the index episode.
- •Previous clinical diagnosis of heart failure.
- •Permanent atrial fibrillation (AF).
- •Severe valvular or sub-valvular heart disease.
- •Severe peripheral arterial disease in the upper extremities or arteriovenous (AV) shunt in the arm selected for RIPC.
- •Clinical diagnosis of diabetes neuropathy
- •Contraindication for CMR:
- •Severe claustrophobia.
- •Any device which is known to threaten or pose hazard in all MR environments (http://www.mrisafety.com/).
- •Patients with implanted biomedical cardiac devices: pacemakers, ICDs or CRT.
- •Severe thrombocytopenia (platelets <50,000/µL) on any blood test within the previous 3 months.
- •Patients participating in other clinical trials.
- •Impossibility to consent or undergo study follow-ups.
结局指标
主要结局
Rate of anthracycline-induced cardiotoxicity events
时间窗: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Cardiotoxicity event is defined as one of the following: * Drop in LVEF between study CMRs of ≥10 absolute points regardless the absolute value of follow- up ejection fraction (EF). * Drop in LVEF between study CMRs of ≥5 to \<10 absolute points with a follow-up EF value \<50% UNITS: absolute number of patients in each arm qualifying for cardiotoxicity event (i.e. each patient will be qualified at the end of the study as YES/NO).
次要结局
- Change in Quality of Life-Euro Quality of Life-5 dimensions questionnaire(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Rate of tumor regression.(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Change in Quality of Life-Haematological Malignancy Patient-Reported Outcome Measure questionnaire(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Change in Quality of Life-Kansas City Cardiomyopathy Questionnaire(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Primary efficacy endpoint: (RIC vs Sham) Absolute change in LVEF(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Rate of tumor regression.(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Change in Quality of Life-Haematological Malignancy Patient-Reported Outcome Measure questionnaire(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Change in Quality of Life-Euro Quality of Life-5 dimensions questionnaire(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Change in Quality of Life-Kansas City Cardiomyopathy Questionnaire(9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment))
- Rate of Heart Failure Hospitalization(4-60 months)