REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs

Lymphoma Clinical Trial

— RESILIENCE  

Official title:

REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05223413
• Other study ID #: RESILIENCE-H2020
• Status: Recruiting
• Phase: N/A
• Start date: January 18, 2022
• Est. completion date: May 2026

Study information

• Verified date: October 2023
• Source: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
• Contact: Borja Ibañez, MD PhD FESC
• Phone: 914501200
• Email: bibanez[@]cnic.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 608
• Est. completion date: May 2026
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cardiotoxicity
• Lymphoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Denmark	Aarhus University	Aarhus
France	Henri Becquerel	Rouen
Germany	University Hospital Duesseldorf UDUS	Duesseldorf
Netherlands	Amsterdam UMC	Amsterdam
Portugal	Hospital da Luz Learning Health (GLSMED)	Lisboa
Portugal	IPO Lisboa	Lisboa
Spain	Instituto Catalán de Oncología	Barcelona
Spain	Hospital Universitario Virgen de las Nieves	Granada
Spain	Centro Nacional de Investigaciones Cardiovasculares (CNIC)	Madrid
Spain	Fundacion Jimenez Diaz	Madrid
Spain	Hospital General Universitario Gregorio Marañon	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 de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Clinico Universitario de Valladolid	Valladolid

Sponsors (2)

Lead Sponsor	Collaborator
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III	European Commission

Countries where clinical trial is conducted

Denmark,  France,  Germany,  Netherlands,  Portugal,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Secondary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Rate of Heart Failure Hospitalization	Rate of Heart Failure Hospitalization; UNITS: Absolute number of patients in each arm experiencing a heart failure hospitalization	6-42 months

External Links

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