RESILIENCE: REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs
Study Details
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 Non-Hodgkin lymphoma (NHL) patients receiving anthracyclines.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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 Non-Hodgkin lymphoma (NHL) 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).
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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).
- 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).
- 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)
- 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 Heart Failure Hospitalization [6-42 months]
Rate of Heart Failure Hospitalization UNITS: Absolute number of patients in each arm experiencing a heart failure hospitalization
Eligibility Criteria
Criteria
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:
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Previous coronary artery disease without evidence of prior myocardial infarction (any of the following):
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Previous coronary revascularisation (PCI or CABG)
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Medical history of previous significant non-revascularized coronary stenosis
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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:
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History of any of the following diseases:
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Any cancer who received treatment
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Previous clinical diagnosis of heart failure.
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Previous diagnosis of acute myocardial infarction.
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Permanent atrial fibrillation (AF).
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Severe valvular or sub-valvular heart disease.
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Severe peripheral arterial disease in the upper extremities or arteriovenous (AV) shunt in the arm selected for RIPC.
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Clinical diagnosis of diabetes
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Contraindication for CMR:
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Severe claustrophobia.
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Any device which is known to threaten or pose hazard in all MR environments (http://www.mrisafety.com/).
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Patients with implanted biomedical cardiac devices: pacemakers, ICDs or CRT.
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Severe thrombocytopenia (platelets <50,000/µL) on any blood test within the previous 3 months.
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Patients participating in other clinical trials.
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Impossibility to consent or undergo study follow-ups.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aarhus University | Aarhus | Denmark | ||
| 2 | Henri Becquerel | Rouen | France | ||
| 3 | University Hospital Duesseldorf UDUS | Duesseldorf | Germany | ||
| 4 | Amsterdam UMC | Amsterdam | Netherlands | ||
| 5 | Hospital da Luz Learning Health (GLSMED) | Lisboa | Portugal | ||
| 6 | IPO Lisboa | Lisboa | Portugal | ||
| 7 | Instituto Catalán de Oncología | Barcelona | Spain | ||
| 8 | Hospital Universitario Virgen de las Nieves | Granada | Spain | ||
| 9 | Centro Nacional de Investigaciones Cardiovasculares (CNIC) | Madrid | Spain | ||
| 10 | Fundacion Jimenez Diaz | Madrid | Spain | ||
| 11 | Hospital General Universitario Gregorio Marañon | Madrid | Spain | ||
| 12 | Hospital Puerta de Hierro | Madrid | Spain | ||
| 13 | Hospital Universitario 12 de Octubre | Madrid | Spain | ||
| 14 | Hospital Universitario Clínico San Carlos | Madrid | Spain | ||
| 15 | Hospital Universitario la Paz | Madrid | Spain | ||
| 16 | Hospital Universitario Ramon y Cajal | Madrid | Spain | ||
| 17 | Hospital Universitario de Salamanca | Salamanca | Spain | ||
| 18 | Hospital Universitario Virgen del Rocío | Sevilla | Spain | ||
| 19 | Hospital Clinico Universitario de Valladolid | Valladolid | Spain |
Sponsors and Collaborators
- Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III
- European Commission
Investigators
- Principal Investigator: Borja Ibañez, MD PhD FESC, CNIC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- RESILIENCE-H2020