REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs

Обзор

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.

Подробное описание

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).

Вмешательства

• Устройство RIPC
  The procedure will be performed by using an electric auto-control device (modified blood pressure monitor for remote ischemic conditioning, Seagull Healthcare Aps, Denmark) for Remote Ischemic Conditioning in the arm. During the inflation period, the blood pressure cuff is inflated to 200 mmHg to stop blood flow in the arm.
• Устройство Simulated RIPC (Sham)
  The procedure will be performed by using an electric auto-control device (modified blood pressure monitor for remote ischemic conditioning, Seagull Healthcare Aps, Denmark) for Remote Ischemic Conditioning in the arm. During the inflation period, the blood pressure cuff is inflated to a low pressure not stopping blood flow in the arm.

Первичные конечные точки

• Rate of anthracycline-induced cardiotoxicity events [Срок оценки: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)]

Вторичные конечные точки (6)

• Primary efficacy endpoint: (RIC vs Sham) Absolute change in LVEF [Срок оценки: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)]
• Rate of tumor regression. [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)]
• Rate of Heart Failure Hospitalization [Срок оценки: 4-60 months]

Критерии участия

Критерии включения

≥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)

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Испания · 17 центров

• Hospital Universitario Príncipe de Asturias — Alcalá de Henares
• Centro Medico Teknon — Barcelona
• Instituto Catalán de Oncología — Barcelona
• Hospital Universitario Virgen de las Nieves — Granada
• Centro Nacional de Investigaciones Cardiovasculares (CNIC) — Madrid
• Fundacion Jimenez Diaz — Madrid
• Hospital General Universitario Gregorio Marañon — Madrid
• Hospital Infanta Leonor — Madrid
• … и ещё 9 центров

Франция · 2 центра

• Hospital Jaques Monod, El Havre — Montivilliers
• Henri Becquerel — Rouen

Португалия · 2 центра

• Hospital da Luz Learning Health (GLSMED) — Lisbon
• IPO Lisboa — Lisbon

Дания · 1 центр

• Aarhus University — Aarhus

Германия · 1 центр

• University Hospital Duesseldorf UDUS — Düsseldorf

Нидерланды · 1 центр

• Amsterdam UMC — Amsterdam

Идентификаторы

NCT: NCT05223413 · RESILIENCE-H2020

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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