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REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE)

Primary Purpose

Anthracycline-induced Cardiac Toxicity, Lymphoma

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
RIPC
Simulated RIPC (Sham)
Sponsored by
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Anthracycline-induced Cardiac Toxicity

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

≥18 years old First NHL 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 without evidence of prior myocardial infarction (any of the following):
  • Previous coronary revascularisation (PCI or CABG)
  • Medical history of previous significant non-revascularized coronary stenosis
  • 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 Signed Informed Consent Form (ICF)

Exclusion Criteria:

  • History of any of the following diseases:

    • Any cancer who received treatment
    • Previous clinical diagnosis of heart failure.
    • Previous diagnosis of acute myocardial infarction.
    • 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
  • 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.

Sites / Locations

  • Aarhus UniversityRecruiting
  • Henri BecquerelRecruiting
  • University Hospital Duesseldorf UDUSRecruiting
  • Amsterdam UMC
  • Hospital da Luz Learning Health (GLSMED)Recruiting
  • IPO LisboaRecruiting
  • Instituto Catalán de OncologíaRecruiting
  • Hospital Universitario Virgen de las NievesRecruiting
  • Centro Nacional de Investigaciones Cardiovasculares (CNIC)Recruiting
  • Fundacion Jimenez DiazRecruiting
  • Hospital General Universitario Gregorio MarañonRecruiting
  • Hospital Puerta de Hierro
  • Hospital Universitario 12 de OctubreRecruiting
  • Hospital Universitario Clínico San CarlosRecruiting
  • Hospital Universitario la PazRecruiting
  • Hospital Universitario Ramon y CajalRecruiting
  • Hospital Universitario de SalamancaRecruiting
  • Hospital Universitario Virgen del RocíoRecruiting
  • Hospital Clinico Universitario de ValladolidRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Remote Ischemic Conditioning

simulated RIPC (Sham)

Arm 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

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.

Outcomes

Primary Outcome Measures

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), %

Secondary Outcome Measures

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).
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).
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)
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)
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)
Rate of Heart Failure Hospitalization
Rate of Heart Failure Hospitalization UNITS: Absolute number of patients in each arm experiencing a heart failure hospitalization

Full Information

First Posted
December 20, 2021
Last Updated
October 16, 2023
Sponsor
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Collaborators
European Commission
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1. Study Identification

Unique Protocol Identification Number
NCT05223413
Brief Title
REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs
Acronym
RESILIENCE
Official Title
REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 18, 2022 (Actual)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
May 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
Collaborators
European Commission

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anthracycline-induced Cardiac Toxicity, Lymphoma

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
608 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Remote Ischemic Conditioning
Arm Type
Active Comparator
Arm 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
Arm Title
simulated RIPC (Sham)
Arm Type
Sham Comparator
Arm 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.
Intervention Type
Device
Intervention Name(s)
RIPC
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Simulated RIPC (Sham)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Primary efficacy endpoint: (RIC vs Sham) Absolute change in LVEF
Description
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), %
Time Frame
9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Secondary Outcome Measure Information:
Title
Rate of anthracycline-induced cardiotoxicity events
Description
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).
Time Frame
9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Title
Rate of tumor regression.
Description
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).
Time Frame
9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Title
Change in Quality of Life-Haematological Malignancy Patient-Reported Outcome Measure questionnaire
Description
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)
Time Frame
9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Title
Change in Quality of Life-Euro Quality of Life-5 dimensions questionnaire
Description
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)
Time Frame
9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Title
Change in Quality of Life-Kansas City Cardiomyopathy Questionnaire
Description
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)
Time Frame
9 weeks after the last chemotherapy cycle (anticipated to be between 150 and 200 days from enrollment)
Title
Rate of Heart Failure Hospitalization
Description
Rate of Heart Failure Hospitalization UNITS: Absolute number of patients in each arm experiencing a heart failure hospitalization
Time Frame
6-42 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Borja Ibañez, MD PhD FESC
Phone
914501200
Ext
4302
Email
bibanez@cnic.es
First Name & Middle Initial & Last Name or Official Title & Degree
Noemi Escalera
Phone
914501200
Ext
5401
Email
nescalera@cnic.es
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Borja Ibañez, MD PhD FESC
Organizational Affiliation
CNIC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aarhus University
City
Aarhus
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Damore
Facility Name
Henri Becquerel
City
Rouen
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vincent Camus
Facility Name
University Hospital Duesseldorf UDUS
City
Duesseldorf
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florian Boenner
First Name & Middle Initial & Last Name & Degree
Malte Kelm
Facility Name
Amsterdam UMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Jose Kersten
Facility Name
Hospital da Luz Learning Health (GLSMED)
City
Lisboa
Country
Portugal
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Antonio Ferreira
Facility Name
IPO Lisboa
City
Lisboa
Country
Portugal
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Gomes
Facility Name
Instituto Catalán de Oncología
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Gonzalez
Facility Name
Hospital Universitario Virgen de las Nieves
City
Granada
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jose Manuel Puerta
Facility Name
Centro Nacional de Investigaciones Cardiovasculares (CNIC)
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Borja Ibañez
Facility Name
Fundacion Jimenez Diaz
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raul Córdoba
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana Bastos
Facility Name
Hospital Puerta de Hierro
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Belen Navarro
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ana Jimenez
Facility Name
Hospital Universitario Clínico San Carlos
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Celina Benavente
Facility Name
Hospital Universitario la Paz
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Miguel Canales
Facility Name
Hospital Universitario Ramon y Cajal
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Javier Lopez
Facility Name
Hospital Universitario de Salamanca
City
Salamanca
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alejandro Martin
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillermo Rodriguez
Facility Name
Hospital Clinico Universitario de Valladolid
City
Valladolid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Jesús Peñarrubia

12. IPD Sharing Statement

Links:
URL
http://resilience-h2020.com
Description
web page

Learn more about this trial

REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs

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