NRP + ex Situ HMPO2 vs NRP Alone in DCD Kidney Transplantation

The trial is designed as a randomised, controlled, multicentre superiority trial with the primary endpoint of eGFR at one year after kidney transplant. The trial will be carried out in the four academic hospitals with renal transplant programs in Sweden: Stockholm, Gothenburg, Malmo and Uppsala. Randomisation 1:1 and eCRF will be done using RedCap.

Each eligible kidney for the trial will be randomised 1:1 between the following groups:

Group 1 - control group: Following in-situ NRP and in-situ flushing, the kidney will be packed in a storage box and stored on ice until back-table preparation before transplantation at the recipient centre.

Group 2 - intervention group: Following in-situ NRP and in-situ flushing, the kidney will be placed on the Kidney Assist Transporter HMPO2 device and perfused with oxygenated Belzers Machine Preservation Solution at a pulsatile pressure of 25 mmHg starting immediately after retrieval until back-table preparation before kidney transplantation at the transplant centre. Oxygen will be delivered at a rate of 100 ml/min via an oxygenator from a portable oxygen cylinder, resulting in a partial oxygen tension in the perfusate of 90 kPa (for reference, +/- 675 mmHg).

Kidney donors All standard allocation rules and recipient matching will be undertaken according to standard practice. Randomisation 1:1 of the kidneys between the two study arms will be done once the recovery of the organs is completed successfully with NRP and both kidneys are accepted for transplant. One kidney will be allocated to static cold storage preservation arm and the other to HMPO2 arm. If both kidneys are transplanted at the same centre, an additional stratification will determine which kidney will be transplanted first. If only one kidney is recovered or allocated to a Swedish centre, this will be randomised following a kidney alone randomisation procedure. Kidneys will be shared between the four transplant centres according to clinical protocols in place. The care of the donor and the NRP recovery procedure, will be performed according to standard practice.

Kidney recipients Written consent regarding trial participation will be sought from all patients on the waiting list or for the newly listed patients, at the time of listing. Kidney recipients will be selected according to national organ allocation rules, independent of participation in the trial. Surgery will be performed according to local clinical protocols and postoperative care managed according to standard of care. During the follow-up, biopsies will be performed according to the local standard of care and if indicated for clinical management. At the end of the one year follow up, a renal biopsy will be taken to determine the iBox score. The clinical care of the patients will reflect the current standard of care at the recipient hospital with no deviation from routine care protocols.

Modifications

• Since the intervention is a one-time event occurring prior to transplantation, the assigned study intervention will not need to be modified or discontinued once the kidney is transplanted.
• If the machine fails, the kidney will be end up being cold stored on the device. If these kidneys are transplanted, the recipient will still be included in the secondary modified intention-to-treat analysis according to the treatment actually received.

Adherence Since the intervention occurs prior to the transplantation procedure, there are no measures to assure adherence to study intervention. For data collection, all variables beside the 1-year study biopsy are part of standard of care after kidney transplantation so no additional measures are needed. As one year biopsy is not part of routine care in all centres, all study participants will be consented for the biopsy and will have the option to opt out. A subgroup analysis will be undertaken in those patients for whom a one year biopsy is undertaken. All study participants that consented to participation, will receive a written invitation for the biopsy performed at the local centre.

Follow up visits All follow-up visits and endpoint measures besides the 1-year biopsy are standard of care after renal transplantation in Sweden. The patient will receive an invitation for the 1-year biopsy if they've signed the informed consent for biopsy. Data will be collected from patient medical records after informed consent. Data will be accessed in medical records.

During the trial the following data will be retrieved:

• Donor demographics
• Recipient demographics
• NRP and Preservation parameters
• Surgical and clinical variables
• Graft and patient survival
• Follow-up data (including complications, adverse events, biopsy and biochemical markers)

Variables and data collection Data will be collected on RedCap for the trial. All blood sampling will be undertaken as part of the routine clinical follow-up with additional study specific samples as above.

Recruitment Approximately 100 kidney transplants from DCD donors are performed each year in Sweden. Although these numbers are expected to increase by about 20%-30% over the next 3 years, researchers planned recruitment on the current level of activity and are confident that 107 eligible kidney pair recipients will be recruited in 36 months (allowing for a the drop out in follow-up and for organs allocated in Scandiatransplant in the STAMP exchange and the payback system between countries). The researchers therefore estimate an enrolment of about 214 DCD kidney transplants during the study period.

Study duration The study is planned to start in January 2027 and with patient inclusion between March 2027 and December 2029, with a one year follow until December 2030. Written summary and presentation of findings in peer-reviewed journals is planned to be completed by March 2031.

Inclusion criteria

Donor kidneys:

• All DCD donors in Sweden with consent for organ donation and where organ recovery is undertaken with NRP.
• Kidney deemed transplantable by donor surgeon and responsible transplant surgeon (not discarded before or during procurement)

Recipients:

• All adult patients (>18 yrs old) eligible for renal transplantation during study duration.
• Recipient consented for surgery, matched to a DCD kidney.

Exclusion criteria

Donor kidneys:

• Kidney allocated outside of Sweden according to Scandiatransplant allocation rules.

Recipients:

• Paediatric patients (<18 yrs old).
• Participation in other clinical drug or medical devices trials.
• Patient subject to combined transplant of kidney + other organ.