Clinical trial NCT03991923: Non-ischemic Preservation of the Donor Heart in Heart Transplantation
Official title: Non-ischemic Preservation of the Donor Heart in Heart Transplantation - a Randomized, Controlled, Multicenter Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Heart Transplantation
Keywords: Non Ischemic Heart Preservation (NIHP)
Ischemic cold static storage of donor hearts (ICSS)
Lead sponsor: XVIVO Perfusion
Sponsor class: INDUSTRY
First posted: 2019-06-19
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria recipient:

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

Inclusion criteria donor:

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

Exclusion Criteria recipient:

* 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)

Exclusion criteria donor:

* Previous sternotomy
* DCD hearts

Primary outcomes:
measure: 30 days mortality and 30 days graft dysfunction
timeFrame: 30 days
Secondary outcomes:
measure: 1 year mortality and 1 year graft dysfunction
timeFrame: 1 year
measure: 30 days and 1 year mortality and graft dysfunction
timeFrame: 30 days and 1 year
measure: CKMB
timeFrame: 3 days
measure: TnI
timeFrame: 3 days
measure: ProBNP
timeFrame: 3 days
measure: Stay in ICU
timeFrame: 1 year
measure: Cardiac Transplant Events
timeFrame: 1 year
measure: Postoperative use of mechanical circulatory support
timeFrame: 1 year
measure: Postoperative duration of mechanical circulatory support
timeFrame: 1 year
measure: Overall success/failure 30 days
timeFrame: 30 days
measure: Overall success/failure 1 year
timeFrame: 1 year
measure: ECHO data (Left ventricular ejection fraction)
timeFrame: 24 hours
measure: ECHO data (Left ventricular ejection fraction)
timeFrame: 1 week
measure: ECHO data (Left ventricular ejection fraction)
timeFrame: 6 months
measure: ECHO data (Left ventricular ejection fraction)
timeFrame: 1 year
measure: ECHO data (Right ventricular ejection fraction)
timeFrame: 24 hours
measure: ECHO data (Right ventricular ejection fraction)
timeFrame: 1 week
measure: ECHO data (Right ventricular ejection fraction)
timeFrame: 6 months
measure: ECHO data (Right ventricular ejection fraction)
timeFrame: 1 year
measure: ECHO data (Tricuspid annular plane systolic excursion)
timeFrame: 24 hours
measure: ECHO data (Tricuspid annular plane systolic excursion)
timeFrame: 1 week
measure: ECHO data (Tricuspid annular plane systolic excursion)
timeFrame: 6 months
measure: ECHO data (Tricuspid annular plane systolic excursion)
timeFrame: 1 year
Other outcomes:
measure: Serious adverse device effects
timeFrame: 1 year
measure: Adverse device effects
timeFrame: 1 year
measure: Device dysfunction resulting in loss of transplantable heart
timeFrame: 12 hours
measure: Intra operative details; duration of ECC
timeFrame: 12 hours
measure: Intra operative details; duration of cross clamp
timeFrame: 12 hours
measure: Intra operative details; duration of surgery
timeFrame: 12 hours
measure: Intra operative details; attempts to wean off ECC
timeFrame: 12 hours
measure: Intra operative details; need for inotropic support
timeFrame: 12 hours
measure: Intra operative details; need for pulmonary vasodilator
timeFrame: 12 hours
measure: Intra operative details; defibrillations
timeFrame: 12 hours
measure: Intra operative details; arryhythmias
timeFrame: 12 hours
measure: Intra operative details; conduction abnormalities
timeFrame: 12 hours
measure: Intra operative details; Left ventricular ejection fraction (LVEF)
timeFrame: 12 hours
measure: Intra operative details; Right ventricular ejection fraction (RVEF)
timeFrame: 12 hours
measure: Intra operative details; Mitral valve regurgitations
timeFrame: 12 hours
measure: Intra operative details; Tricuspid valve regurgitations
timeFrame: 12 hours
measure: Arterial blood gas lactate
timeFrame: 6 hours
measure: Arterial blood gas lactate
timeFrame: 24 hours
measure: Pro-BNP during follow up
timeFrame: 1 year
Locations:
city: Wien
country: Austria
facility: Allgemeines Krankenhaus der Stadt Wien
city: Leuven
country: Belgium
facility: UZ Leuven
state: Flemish Brabant
city: Paris
country: France
facility: Institut de cardiologie, Chirurgie thoracique et cardiovasculaire La Pitié Salpetrière
state: Paris Cedex
city: Paris
country: France
facility: Hôpital Bichat Claude-Bernard
city: München
country: Germany
facility: Klinikum der Universität München
state: Bavaria
city: Berlin
country: Germany
facility: Deutschen Herzzentrum Berlin
state: Brandenburg
city: Bad Oeynhausen
country: Germany
facility: Universitätsklinik der Ruhr-Universität Bochum
city: Duesseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf
city: Hanover
country: Germany
facility: Hannover Medical School
city: Padova
country: Italy
facility: Azienda osedalaria di Padova
state: Padova PD
city: Madrid
country: Spain
facility: Hospital Puerto de Hierro
state: Majadahonda Madrid
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
state: Västra Götalands regionen
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
state: Newcastle upon Tyne
city: Birmingham
country: United Kingdom
facility: Queen Elisabeth Hospital
city: Cambridge
country: United Kingdom
facility: Royal Papworth Hospital
Study officials:
affiliation: UZ Leuven
name: Filip Rega, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: