Non-ischemic Preservation of the Donor Heart in Heart Transplantation
- Conditions
- Heart Transplantation
- Interventions
- Device: XVIVO heart preservation devicesDevice: Standard ICSS
- Registration Number
- NCT03991923
- Lead Sponsor
- XVIVO Perfusion
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 230
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Non-ischemic heart preservation (NIHP) XVIVO heart preservation devices Continous cold cardioplegic perfusion of hearts Ischemic cold static storage (ICSS) Standard ICSS Standard preservation technique
- Primary Outcome Measures
Name Time Method 30 days mortality and 30 days graft dysfunction 30 days The Primary End-Point is defined as time-to-first-event of cardiac related death, moderate or severe primary graft dysfunction of the left ventricle or primary graft dysfunction of the right ventricle (according to Kobashigawa et al., 2014), acute cellular rejection ≥2R (according to Stewart et al., 2005) or graft failure (use of mechanical circulatory support or retransplantation) within 30 days.
- Secondary Outcome Measures
Name Time Method Stay in ICU 1 year Length of Stay at Intensive Care Unit, reported as number of days
TnI 3 days Tropinin I (TnI) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
1 year mortality and 1 year graft dysfunction 1 year The key secondary endpoint is defined as time-to-first-event of either any cause of death, moderate or severe PGD-LV or PGD-RV (according to Kobashigawa et al., 2014), acute cellular rejection ≥2R (according to Stewart et al., 2005) or graft failure (use of mechanical circulatory support or retransplantation) or CAV ≥ 1 (according to Mehra, 2010) within 12 months.
30 days and 1 year mortality and graft dysfunction 30 days and 1 year The individual variables included in the composite primary endpoint at 30 days and 1 year analyzed as time-to-first-event.
ProBNP 3 days Pro Brain Natriuretic Protein (ProBNP) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
Cardiac Transplant Events 1 year Incidence of Major Adverse Cardiac Transplant Events
ECHO data (Left ventricular ejection fraction) 1 year ECHO data with Left ventricular ejection fraction in percentage 1 year after transplantation
ECHO data (Tricuspid annular plane systolic excursion) 1 year ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 year after transplantation
Postoperative use of mechanical circulatory support 1 year Incidence of use of postoperative mechanical circulatory support, reported as number of days
Overall success/failure 1 year 1 year Success is defined as a recipient that are transplanted and alive at 1 year without any of the complication given in key secondary endpoint before 1 year.
ECHO data (Right ventricular ejection fraction) 1 year ECHO data with Right ventricular ejection fraction in percentage 1 year after transplantation
CKMB 3 days Creatine kinase MB (CKMB) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
Postoperative duration of mechanical circulatory support 1 year Duration of use of postoperative mechanical circulatory support, reported as number of days
Overall success/failure 30 days 30 days Success is defined as a recipient that are transplanted and alive at 30 days without any of the complication in the primary endpoint before 30 days.
Trial Locations
- Locations (15)
Hannover Medical School
🇩🇪Hanover, Germany
Azienda osedalaria di Padova
🇮🇹Padova, Padova PD, Italy
Allgemeines Krankenhaus der Stadt Wien
🇦🇹Wien, Austria
UZ Leuven
🇧🇪Leuven, Flemish Brabant, Belgium
Institut de cardiologie, Chirurgie thoracique et cardiovasculaire La Pitié Salpetrière
🇫🇷Paris, Paris Cedex, France
Deutschen Herzzentrum Berlin
🇩🇪Berlin, Brandenburg, Germany
Hôpital Bichat Claude-Bernard
🇫🇷Paris, France
Klinikum der Universität München
🇩🇪München, Bavaria, Germany
Universitätsklinik der Ruhr-Universität Bochum
🇩🇪Bad Oeynhausen, Germany
Universitätsklinikum Düsseldorf
🇩🇪Duesseldorf, Germany
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