Non-ischemic Preservation of the Donor Heart in Heart Transplantation

NCT ID: NCT03991923

Last Updated: 2025-04-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-25
• Study Completion Date: 2028-12-31

Brief Summary

The study intends to compare standard ischemic cold static storage (ICSS) of retrieved hearts intended to be transplanted, to non-ischemic heart preservation (NIHP) in a randomized clinical multicentre trial. The primary hypothesis is that the non-ischemic hypothermic cardioplegic preservation (NIHP) is safe and superior to ischemic cold static storage (ICSS) of donor hearts. The study will investigate the safety and superiority of the new methodology in terms of improved immediate and prolonged organ function in adult heart transplanted patients.

Detailed Description

This study will investigate if non-ischemic heart preservation (NIHP) with the XVIVO heart preservation devices could improve clinical outcome of patients receiving hearts after use of the technology compared to after use of standard cold ischemic preservation. This will be investigated in a European multicentre randomized controlled clinical trial. For technical reasons, blinding to the involved clinical personnel is not possible, however, biopsies will be blinded to study pathologists. The trial will include 202 recipients that have been randomized through their heart donor. The primary outcome of the study is a clinically relevant composite including graft survival, primary graft dysfunction, rejection and use of circulatory mechanical support, within 30 days and also including Cardiac Allograft Vasculopathy within 12 months. As secondary outcomes, molecular markers related to cardiac injury CKMB, ProBNP and TNI will be investigated as well as markers of the inflammatory response. Safety aspects such as effect on other organs and machine defects will also be monitored. The study population is adults, listed for heart transplantation and donors accepted as heart donors according to standard hospital procedures. Specific recipient exclusion criteria related to pre-transplant ECMO support, patients undergoing pre-transplant desensitization protocol, patients with Grown-Up Congenital Heart Disease, patients with severe kidney or liver dysfunction, patients with septicaemia, and patients diagnosed with Systemic Lupus Erythematous, sarcoidosis or amyloidosis are excluded. Cardiac death donors and donors with previous sternotomy are excluded. The study hypothesis is that NIHP better preserves the endothelium and myocyte function of the heart resulting in improved short- and medium-term recipient outcome, without inducing any new significant risks to the retrieved heart or the recipient. This is believed to be accomplished through continuous oxygenation of the heart via perfusion of the coronary arteries using an optimized preservation solution, mimicking the normal environment for the endothelium.

Conditions

Heart Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Non-ischemic heart preservation (NIHP)

Continous cold cardioplegic perfusion of hearts

Group Type: EXPERIMENTAL

XVIVO heart preservation devices

Intervention Type: DEVICE

The intervention is to preserve hearts during transportation cold, cardioplegic and non-ischemic, with a high oncotic and hormone supplemented perfusate.

Ischemic cold static storage (ICSS)

Standard preservation technique

Group Type: ACTIVE_COMPARATOR

Standard ICSS

Intervention Type: DEVICE

Cold static preservation using standard preservation solution

Interventions

XVIVO heart preservation devices

The intervention is to preserve hearts during transportation cold, cardioplegic and non-ischemic, with a high oncotic and hormone supplemented perfusate.

Intervention Type: DEVICE

Standard ICSS

Cold static preservation using standard preservation solution

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years
• Signed informed consent form
• Listed for heart transplantation

• Age ≥18 and ≤70 years
• Accepted as heart donor by the transplant team
• (Research consent from the donor if required in country)

Exclusion Criteria

• Previous solid organ transplantation
• Grown-up congenital heart disease (GUCH)
• Kidney failure eGFR<40 at listing, calculated by CDK-EPI Creatinine, or ultrafiltration or dialysis or rapidly deteriorating kidney function due to a diagnosed renal disease
• Coagulopathy due to known hepatic disease or heparin induced thrombocytopenia
• Subject diagnosed with Systemic Lupus Erythematous, sarcoidosis or amyloidosis
• Known ongoing septicemia defined as positive blood culture immediately prior to the transplant (including with a durable VAD)
• Incompatible blood group
• Not able to understand the information provided during the informed consent procedure
• Combined organ transplantation candidates
• Subject already enrolled in another transplant related intervention study
• Subjects under pre-transplant desensitization protocol (including plasma exchange in conjunction with the transplant surgery)
• Mechanical circulatory support pre-transplantation (except durable Left ventricular assist device or Intra-aortic balloon pump)

• Previous sternotomy
• DCD hearts

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

XVIVO Perfusion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Filip Rega, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

Allgemeines Krankenhaus der Stadt Wien

Vienna, , Austria

UZ Leuven

Leuven, Flemish Brabant, Belgium

Institut de cardiologie, Chirurgie thoracique et cardiovasculaire La Pitié Salpetrière

Paris, Paris Cedex, France

Hôpital Bichat Claude-Bernard

Paris, , France

Klinikum der Universität München

München, Bavaria, Germany

Deutschen Herzzentrum Berlin

Berlin, Brandenburg, Germany

Universitätsklinik der Ruhr-Universität Bochum

Bad Oeynhausen, , Germany

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Hannover Medical School

Hanover, , Germany

Azienda osedalaria di Padova

Padua, Padova PD, Italy

Hospital Puerto de Hierro

Madrid, Majadahonda Madrid, Spain

Sahlgrenska University Hospital

Gothenburg, Västra Götalands Regionen, Sweden

Freeman Hospital

Newcastle, Newcastle upon Tyne, United Kingdom

Queen Elisabeth Hospital

Birmingham, , United Kingdom

Royal Papworth Hospital

Cambridge, , United Kingdom

Countries

Austria; Belgium; France; Germany; Italy; Spain; Sweden; United Kingdom

References

Rega F, Lebreton G, Para M, Michel S, Schramm R, Begot E, Vandendriessche K, Kamla C, Gerosa G, Berman M, Boeken U, Clark S, Ranasinghe A, Ius F, Forteza A, Pivodic A, Hennig F, Guenther S, Zuckermann A, Knosalla C, Dellgren G, Wallinder A; NIHP2019 investigators. Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial. Lancet. 2024 Aug 17;404(10453):670-682. doi: 10.1016/S0140-6736(24)01078-X.

Reference Type: DERIVED

PMID: 39153817 (View on PubMed)

Brouckaert J, Dellgren G, Wallinder A, Rega F. Non-ischaemic preservation of the donor heart in heart transplantation: protocol design and rationale for a randomised, controlled, multicentre clinical trial across eight European countries. BMJ Open. 2023 Dec 28;13(12):e073729. doi: 10.1136/bmjopen-2023-073729.

Reference Type: DERIVED

PMID: 38154894 (View on PubMed)

Other Identifiers

NIHP2019

Identifier Type: -

Identifier Source: org_study_id