Mechanistic evaluation of machine perfusion strategies in donation after circulatory death liver transplantation
The patient population consists of adults listed for elective liver transplantation
Open-label, prospective, three-arm, phase II randomized clinical trial investigating the effects of 3 different preservation techniques on pre-defined functional and mechanistic endpoints in DCD liver transplantation. Consecutive circulatory death donors (DCD) assigned to recipients consented to participate in the trial will be randomized to one of three arms (n=12 per arm): Arm 1 (Static cold storage: SCS). The donor liver will be flushed in situ with 4 °C UW preservation solution (or HTK) through the aorta and portal vein, retrieved, and transported to the transplant centre in an icebox. Arm 2 (Normothermic regional perfusion: NRP). The donor aorta and inferior cava vein will be cannulated, followed by descending thoracic aorta cross-clamp and initiation of perfusion (Cardiohelp device) with the donor’s own blood at 37 °C for 2 h (while monitoring pump flow, venous O2 saturation, lactate and ALT), followed by in-situ flush with 4 °C preservation solution as in the SCS arm. Arm 3 (Hypothermic oxygenated perfusion: HOPE). The liver will be retrieved and preserved as in the SCS arm. Then, on arrival to the transplant unit, the portal vein and hepatic artery will be cannulated, and the liver perfused with hypothermic oxygenated solution (VitaSmart device) for 2 h. All livers, regardless of their allocated Arm, will then be perfused under normothermic machine perfusion conditions for at least 4 h before transplantation. Primary analysis will be as per protocol and include all livers that are perfused under normothermic machine perfusion (NMP) conditions for at least 4 h. A secondary analysis including recipient outcomes will include only livers actually transplanted. The overall study duration will be up to 30 months. The study participant recruitment phase will last up to 18 months. Patient follow-up will be 12 months. Clinical outcome data will be collected up to 5 years post-transplant.
Donor inclusion criteria: 1. DCD category III donors considered for abdominal organs-only retrieval 2. Donor age ≥18 years 3. Retrieval procedure allocated to the recruiting site’s NORS team 4. Donor liver accepted for a patient on the recruiting site’s transplant waiting list via the standard offering process 5. Donor BMI <35kg/m2 6. Predicted cold ischaemic time <8 hours 7. Donor family has given consent to use donated liver for research Recipient inclusion criteria: 1. Recipients 18 years of age or older 2. Listed on an elective transplant waiting list 3. Suitable to receive a DCD graft based on the liver listing MDT 4. Willing and able to consent for the study participation
Donor exclusion criteria (at the time of randomisation): 1. Donor is HIV, hepatitis B (HBV HbsAg) or hepatitis C (HCV RNA) positive 2. Any medical condition that, in the opinion of the principal investigator, would interfere with safe completion of the trial Donor exclusion criteria (at the time of retrieval): 1. Liver weight >2.5 kg 2. Macroscopic evidence of advanced fibrosis 3. Functional donor warm ischaemia (defined as a period between the systolic blood pressure <50mmHg and aortic cold flush) >30 minutes 4. Any other clinical issue that in the opinion of the surgical team constitutes a contraindication to proceed with transplantation Recipient exclusion criteria: 1. High-risk surgical candidates (e.g. presence of extensive portomesenteric thrombosis, previous complex upper abdominal surgery) 2. Patients undergoing liver re-transplantation or multi-organ transplantation 3. Patients receiving super-urgent transplantation for acute and acute-on-chronic liver failure