First Clinical Evaluation of Heart Transplantation With Grafts Preserved Using an Ex-vivo Extended Perfusion System

Study Overview
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Brief Summary
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The main objective of PEGASE is to validate the recovery of a satisfactory cardiac function of a transplanted heart after a prolonged period of preservation by an ex-vivo perfusion device. This recovery of cardiac function will have to happen within 15 days after transplantation.

Detailed Description
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Heart transplantation is a scarce resource, only 1 patient among 2 had the opportunity to be grafted in France in 2022. Despite the shortage of organs, some potential heart transplants are currently not recovered because the ischemia duration anticipated before being grafted (from donor to recipient) is too long and not compatible with transplantation, actually limited to 4h, max. Innovation in ex-vivo hypothermic perfusion allows to consider the extension of the graft viability time, thus offering the possibility of extending the pool of heart grafts available to the patients, The study aims to demonstrate the feasibility of taking heart grafts from donors in Martinique and Guadeloupe, transferring them via air transport and then successfully transplanting them to patients hospitalized in France, up to 14 hours later, using an ex-vivo cold perfusion device to protect the heart during transport. Patients involved in this study will be patients in desperate need of transplantation, with no chance of receiving it, due to the French transplant allocation policy.

Official Title
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Première Evaluation Clinique de la Transplantation Cardiaque de Greffons préservés à l'Aide d'un Système de Perfusion Ex-vivo prolongée

Conditions
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Heart Transplantation

Intervention / Treatment
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* Procedure: Heart transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18 years of age Patients suffering from irreversible terminal heart failure with a medical indication for heart transplantation but who cannot be transplanted (per the graft allocation policy in France) or assisted (technical impossibility, contraindication, patient's refusal) and for whom a favourable and motivated opinion from the Multidisciplinary Consultation Meeting (RCP) of the cardiac surgery department of the Hospital Pitié-Salpêtrière has been made Having given their informed consent in writing Exclusion Criteria: Technical obstacles which would generate an excessive surgical risk for the patient according to the medical opinion such as comorbidities or associated pathology not compatible with a transplant Known ongoing sepsis, defined as positive blood culture immediately prior to transplant (including with ventricular assist device) Candidate patient for Combined Organ Transplantation Patient protected by law (guardianship, curatorship, deprived of liberty) No affiliated with or entitled to a French social security scheme (AME included) Pregnant or breast-feeding female Current participation in another interventional study (category 1 of French Jardé law) or being in the exclusion period at the end of a previous study Patient unable to understand the information provided during the informed consent procedure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Patients with end-stage Heart Failure<br> | Procedure: Heart transplantation<br>* Heart transplantation in patients who have obtained a favourable and motivated opinion from the Multidisciplinary Consultation Meeting (RCP) of the cardiac surgery department of the Hospital Pitié-Salpêtrière<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Short term recovery of Cardiac function | Cardiac index greater than 2.5 L/min/m2 without inotropic support and/or temporary circulatory assistance (ECMO, IMPELLA, BCPIA) measured by thermodilution (SWAN-GANZ catheter) or echocardiography | Within 15 days after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | 15 days, 30 days, 9 months, 6 months and 12 months | 
| Absence of cardiac deaths | Patient who survived or died for a reason other than failure of cardiac function | 15 days, 30 days, 3 months, 6 months and 12 months | 
| Cardiac function recovery | Cardiac index greater than 2.5 L/min/m2 without inotropic support and/or temporary circulatory assistance (ECMO, IMPELLA, BCPIA) measured by thermodilution (SWAN-GANZ catheter) or echocardiography | 30 days, 3months, 6 months and 12 months | 
| Adverse events after transplant | moderate or severe primary graft dysfunction (according to ISHLT consensus), acute cell rejection >2R, VAD >1, long-term circulatory support (LVAD, BiVAD, TAH) | 15 days and 12 months | 
| Myocardial preservation | Absence of significant edema (pre- and post-preservation graft weight) | during the procedure/surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart transplantation, XVIVO perfusion