REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs

Not Applicable

Recruiting

Conditions: Lymphoma
Anthracycline-induced Cardiac Toxicity

Interventions: Device: RIPC
Device: Simulated RIPC (Sham)

Registration Number: NCT05223413

Lead Sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

Brief Summary: 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.

Detailed 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 24 months (range: 6 to 42 months).

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 608

Inclusion Criteria

≥18 years old First Lymphoma diagnosis Scheduled to undergo ≥5 chemotherapy cycles including 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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Remote Ischemic Conditioning	RIPC	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
simulated RIPC (Sham)	Simulated RIPC (Sham)	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.

Primary Outcome Measures

Name	Time	Method
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)	change in LVEF between baseline and any follow-up CMRs, whichever shows worse LVEF UNITS: LVEF is expressed as % LVEF= (LV end-diastolic volume - LV end-systolic volume) / LV end-systolic volume), %

Secondary Outcome Measures

Name	Time	Method
Rate of anthracycline-induced cardiotoxicity events	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).
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)	Haematological Malignancy Patient-Reported Outcome Measure (HM-PRO) questionnaire UNITS: absolute points in the questionnaire. minimum value 0 maximum value 84 the higher the total score, the better (greater the effect on a patient's QoL)
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)	Euro Quality of Life-5 dimensions (EuroQoL-5D) questionnaire: UNITS: absolute points in the questionnaire. minimum value 0 maximum value 100 the higher the total score, the better (greater the effect on a patient's QoL)
Rate of Heart Failure Hospitalization	6-42 months	Rate of Heart Failure Hospitalization UNITS: Absolute number of patients in each arm experiencing a heart failure hospitalization
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)	Kansas City Cardiomyopathy Questionnaire (KCCQ-12) UNITS: absolute points in the questionnaire. minimum value 0 maximum value 65 the higher the total score, the better (greater the effect on a patient's QoL)
Rate of tumor regression.	9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)	Response to chemotherapy UNITS: absolute number of patients in each arm qualifying as responder or no responder (i.e. each patient will be qualified at the end of the study as YES/NO).

Trial Locations

Locations (24): Instituto Catalán de Oncología
🇪🇸
Barcelona, Spain
Hospital Universitario Virgen de las Nieves
🇪🇸
Granada, Spain
Aarhus University
🇩🇰
Aarhus, Denmark
Hospital Jaques Monod, El Havre
🇫🇷
Montivilliers, France
Henri Becquerel
🇫🇷
Rouen, France
University Hospital Duesseldorf UDUS
🇩🇪
Duesseldorf, Germany
Amsterdam UMC
🇳🇱
Amsterdam, Netherlands
Hospital da Luz Learning Health (GLSMED)
🇵🇹
Lisboa, Portugal
IPO Lisboa
🇵🇹
Lisboa, Portugal
Hospital Universitario Príncipe de Asturias
🇪🇸
Alcalá De Henares, Spain
Centro Medico Teknon
🇪🇸
Barcelona, Spain
Centro Nacional de Investigaciones Cardiovasculares (CNIC)
🇪🇸
Madrid, Spain
Fundacion Jimenez Diaz
🇪🇸
Madrid, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸
Madrid, Spain
Hospital Infanta Leonor
🇪🇸
Madrid, Spain
Hospital Puerta de Hierro
🇪🇸
Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Hospital Universitario Clínico San Carlos
🇪🇸
Madrid, Spain
Hospital Universitario la Paz
🇪🇸
Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸
Madrid, Spain
Hospital Universitario Ruber Juan Bravo
🇪🇸
Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸
Salamanca, Spain
Hospital Universitario Virgen del Rocío
🇪🇸
Sevilla, Spain
Hospital Clinico Universitario de Valladolid
🇪🇸
Valladolid, Spain

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