NCT05148715

Calcineurin Inhibitor in NEuRoloGically Deceased Donors to Decrease Kidney delaYed Graft Function (CINERGY)

Calcineurin Inhibitor in NEuRoloGically Deceased Donors to Decrease Kidney delaYed Graft Function (CINERGY)-Pilot Trial

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 414 (estimated)
• Sponsor: Université de Sherbrooke · Academic / Other
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The investigators hypothesize that preconditioning neurologically deceased organ donors with the calcineurin inhibitor tacrolimus will improve short and long-term transplant survival without causing harm. Organ donors will be randomized to receive either 0.02 mg/kg ideal body weight (IBW) of tacrolimus single infusion or placebo before organ recovery. All corresponding recipients are enrolled and data is collected up to 7 days post-transplant to determine graft function and at 1 year to collect outcomes of vital status, re-transplantation and dialysis. The CINERGY Pilot Trial assesses feasibility for the main trial.

Detailed description

Background: Organ donation saves lives, and improves quality of life for thousands of people. But organ donation falls short of expectations for some patients who suffer early graft loss. During organ donation surgery, the supply of blood with oxygen and nutrients is suspended. When restored during transplant surgery, a cascade of inflammation perturbs the newly transplanted organ -causing ischemia-reperfusion injury. When severe, it can hinder transplant function in the early post-operative period, lead to profound critical illness, increase the risks of transplant rejection and chronic disease, and reduce the transplant lifespan. Administration of tacrolimus, a calcineurin inhibitor, to neurologically deceased donors may reduce ischemia-reperfusion injury in transplant recipients. Objectives: The CINERGY Pilot Trial will test the feasibility of comparing tacrolimus to placebo for the prevention of delayed graft function in kidney recipients and establish the foundation for a large, multi-centre randomized controlled trial (RCT). Methods: 90 neurologically deceased kidney donors will be randomized to either tacrolimus (0.02 mg/kg) or the corresponding placebo 4-8 hours before organ recovery. To be included in the CINERGY Pilot RCT, donors will need to meet inclusion criteria. All corresponding recipients are enrolled and their data is collected in the first 7 days and at 12 months after transplantation. Outcomes: Feasibility: Donor accrual rate and consent rate of organ recipients. Safety: acute kidney injury, hyperkalemia and anaphylaxis in donors and recipients. Clinical: graft function within 7 days in all recipients, vital status, re-transplantation and need for dialysis at 12 months. Relevance: This pilot study will inform the feasibility and design of a larger trial. Moreover, the CINERGY Pilot RCT will pave the way for future trials linking organ donation and transplantation across Canada.

Conditions

• Organ Transplant Failure or Rejection
• Brain Death
• Ischemic Reperfusion Injury

Interventions

Type	Name	Description
DRUG	Tacrolimus	Single dose intravenous tacrolimus over 4 hour infusion at a dose of 0.02 mg/kg ideal body weight diluted with 0.9% sodium chloride starting 4-8 hours before scheduled organ recovery.
DRUG	Placebo	Single dose of intravenous 0.9% sodium chloride over 4 hour infusion, starting 4-8 hours before scheduled organ recovery.

Timeline

• Start date: 2022-07-11
• Primary completion: 2025-12-01
• Completion: 2026-01-01
• First posted: 2021-12-08
• Last updated: 2025-04-17

Locations

9 sites across 1 country: Canada