REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE)

Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Status: Enrolling

Conditions: Lymphoma; Anthracycline-induced Cardiac Toxicity

Treatments: Device: Simulated RIPC (Sham); Device: RIPC

Study type: Interventional

Funder types: Other

Identifiers

NCT05223413

RESILIENCE-H2020

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 608 estimated patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

≥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)

Exclusion criteria

• 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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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608 participants in 2 patient groups

Remote Ischemic Conditioning

Active Comparator group

Description:

Remote Ischemic Conditioning (RIC): Patients will undergo weekly RIC during the entire span of the chemotherapy period. Each RIC session will include four cycles of 5 min blood pressure cuff inflation followed by 5 min deflation

Treatment:

Device: RIPC

simulated RIPC (Sham)

Sham Comparator group

Description:

Control group (Sham): Patients will undergo weekly simulated RIC (sham) during the entire span of the chemotherapy period. Each sham session will include four cycles of 5 min blood pressure cuff inflation followed by 5 min deflation.

Treatment:

Device: Simulated RIPC (Sham)