Clinical trial NCT05223413: REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs
Official title: REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Anthracycline-induced Cardiac Toxicity
Lymphoma
Lead sponsor: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Sponsor class: OTHER
Collaborators: name: European Commission
First posted: 2022-02-04
Enrollment: 608
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomization (1:1) will be stratified by LVEF on baseline CMR (as quantified by CMR core lab /CNIC), by research Centre and by patient's gender.
Primary purpose: PREVENTION

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Primary efficacy endpoint: (RIC vs Sham) Absolute change in LVEF
timeFrame: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Secondary outcomes:
measure: Rate of anthracycline-induced cardiotoxicity events
timeFrame: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
measure: Rate of tumor regression.
timeFrame: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
measure: Change in Quality of Life-Haematological Malignancy Patient-Reported Outcome Measure questionnaire
timeFrame: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
measure: Change in Quality of Life-Euro Quality of Life-5 dimensions questionnaire
timeFrame: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
measure: Change in Quality of Life-Kansas City Cardiomyopathy Questionnaire
timeFrame: 9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
measure: Rate of Heart Failure Hospitalization
timeFrame: 6-42 months
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University
city: Montivilliers
country: France
facility: Hospital Jaques Monod, El Havre
city: Rouen
country: France
facility: Henri Becquerel
city: Duesseldorf
country: Germany
facility: University Hospital Duesseldorf UDUS
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Lisboa
country: Portugal
facility: Hospital da Luz Learning Health (GLSMED)
city: Lisboa
country: Portugal
facility: IPO Lisboa
city: Alcalá De Henares
country: Spain
facility: Hospital Universitario Príncipe de Asturias
city: Barcelona
country: Spain
facility: Centro Medico Teknon
city: Barcelona
country: Spain
facility: Instituto Catalán de Oncología
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Madrid
country: Spain
facility: Centro Nacional de Investigaciones Cardiovasculares (CNIC)
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Infanta Leonor
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario la Paz
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Ruber Juan Bravo
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valladolid
country: Spain
facility: Hospital Clinico Universitario de Valladolid
Study officials:
affiliation: CNIC
name: Borja Ibañez, MD PhD FESC
role: PRINCIPAL_INVESTIGATOR
References: