REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE)

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma; Anthracycline-induced Cardiac Toxicity
• Intervention / Treatment: Device: RIPC; Device: Simulated RIPC (Sham)

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 36 months (range: 6 to 60 months).

• Study Type: Interventional
• Enrollment (Estimated): 608
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Borja Ibañez, MD PhD FESC; Phone Number: 4302 914501200; Email: bibanez@cnic.es
• Study Contact Backup: Name: Noemi Escalera; Phone Number: 5401 914501200; Email: nescalera@cnic.es

Study Locations

• Denmark
  • Aarhus, Denmark
    • Recruiting
    • Aarhus University
    • Contact: Francesco Damore
• France
  • Montivilliers, France
    • Not yet recruiting
    • Hospital Jaques Monod, El Havre
    • Contact: Pierre Lebreton
  • Rouen, France
    • Recruiting
    • Henri Becquerel
    • Contact: Vincent Camus
• Germany
  • Düsseldorf, Germany
    • Recruiting
    • University Hospital Duesseldorf UDUS
    • Contact: Florian Boenner
    • Principal Investigator: Malte Kelm
• Netherlands
  • Amsterdam, Netherlands
    • Not yet recruiting
    • Amsterdam UMC
    • Contact: Marie Jose Kersten
• Portugal
  • Lisbon, Portugal
    • Recruiting
    • Hospital da Luz Learning Health (GLSMED)
    • Contact: Antonio Ferreira
  • Lisbon, Portugal
    • Recruiting
    • Ipo Lisboa
    • Contact: Maria Gomes
• Spain
  • Alcalá de Henares, Spain
    • Not yet recruiting
    • Hospital Universitario Príncipe de Asturias
    • Contact: Julio García Suarez
  • Barcelona, Spain
    • Recruiting
    • Centro Médico Teknon
    • Contact: Antonio Berruezo
  • Barcelona, Spain
    • Recruiting
    • Instituto Catalán de Oncología
    • Contact: Eva Gonzalez
  • Granada, Spain
    • Recruiting
    • Hospital Universitario Virgen de las Nieves
    • Contact: Jose Manuel Puerta
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario 12 de Octubre
    • Contact: Ana Jimenez
  • Madrid, Spain
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
    • Contact: Mariana Bastos
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Miguel Canales
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ramon y Cajal
    • Contact: Javier Lopez
  • Madrid, Spain
    • Recruiting
    • Hospital Puerta de Hierro
    • Contact: Belen Navarro
  • Madrid, Spain
    • Recruiting
    • Fundacion Jimenez Diaz
    • Contact: Raul Córdoba
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Clínico San Carlos
    • Contact: Celina Benavente
  • Madrid, Spain
    • Recruiting
    • Hospital Infanta Leonor
    • Contact: Jose Angel Hernandez Rivas
  • Madrid, Spain
    • Recruiting
    • Centro Nacional de Investigaciones Cardiovasculares (CNIC)
    • Contact: Borja Ibañez
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario Ruber Juan Bravo
    • Contact: Aranzazu Alonso Alonso
  • Salamanca, Spain
    • Recruiting
    • Hospital Universitario de Salamanca
    • Contact: ALEJANDRO MARTIN
  • Seville, Spain
    • Recruiting
    • Hospital Universitario Virgen del Rocio
    • Contact: Guillermo Rodriguez
  • Valladolid, Spain
    • Recruiting
    • Hospital Clinico Universitario de Valladolid
    • Contact: Maria Jesús Peñarrubia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Remote Ischemic Conditioning; 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	Device: 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.
Sham Comparator: 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.	Device: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of anthracycline-induced cardiotoxicity events	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).	9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary efficacy endpoint: (RIC vs Sham) Absolute change in LVEF	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), %	9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Rate of tumor regression.	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).	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	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)	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	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)	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	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)	9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Rate of Heart Failure Hospitalization	Rate of Heart Failure Hospitalization UNITS: Absolute number of patients in each arm experiencing a heart failure hospitalization	4-60 months

Collaborators and Investigators

• Sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
• Collaborators: European Commission
• Investigators: Principal Investigator: Borja Ibañez, MD PhD FESC, CNIC

Publications and helpful links

Helpful Links

• web page

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: December 20, 2021
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Lymphoma
• Other Study ID Numbers: RESILIENCE-H2020

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No