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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Transplantation
• Intervention / Treatment: Procedure: Heart transplantation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guillaume LEBRETON, MD, PhD; Phone Number: +33 0142162979; Email: guillaume.lebreton@aphp.fr
• Study Contact Backup: Name: Pascal LEPRINCE, MD, PhD; Phone Number: +33 0142165632; Email: pascal.leprince@aphp.fr

Study Locations

• France
  • Paris, France, 75013
    • Pitie-Salpêtrière Hospital
    • Contact: Guillaume LEBRETON, MD, PhD; Phone Number: +33 0142162979; Email: guillaume.lebreton@aphp.fr
    • Contact: Zohra ABBOU; Phone Number: +33 0142161625; Email: zohra.abbou@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with end-stage Heart Failure	Procedure: Heart transplantation; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: University Hospital Center of Martinique; Centre Hospitalier Universitaire de Pointe-a-Pitre; ICAN Nutrition Education and Research
• Investigators: Principal Investigator: Guillaume LEBRETON, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: July 24, 2023
• First Submitted That Met QC Criteria: September 11, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Heart transplantation; XVIVO perfusion
• Other Study ID Numbers: APHP220091

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Data are available upon reasonable request. The procedures carried out with the French data regulatory authority (CNIL, Commission Nationale de l'Informatique et des Libertés) do not allow for the transmission of the database, nor do the information and consent documents signed by the patients.

Consultation by the editorial board or interested researchers of individual participant data that underlie the results reported in the article after deidentification may nevertheless be considered, subject to prior determination of the terms and conditions of such consultation and in respect for compliance with the applicable regulations.

• IPD Sharing Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No