CINERGY - Pilot Trial

Calcineurin Inhibitor in NEuRoloGically deceased donors to decrease kidney delaYed graft function (CINERGY)

Background

Organs originating from deceased organ donors carry a high risk of ischemia reperfusion injury, which can lead to delayed graft function (DGF). DGF is associated with long term disease, and graft failure. Animal studies have shown that tacrolimus to donors reduces ischemia-reperfusion injury in transplant recipients to enhance survival. Clinical trials in transplantation support this role, but no studies have yet evaluated the effect of the administration of tacrolimus in donors.

We therefore aim to assess the feasibility of multicentre placebo-controlled randomized main trial with respect to: (i) organ donor accrual rates, (ii) transplant recipient research consent rates, and (iii) completeness of long-term outcome data. We aim to refine our methods prior to a national randomized trial to test our hypothesis.

Rationale for this type of research

Improving donor management through rigorous clinical research is a new frontier for closing the gap between organ supply and demand, and for enhancing survival and quality of life post transplantation. This research poses uniquely challenging ethical and logistical hurdles, which our group is addressing, creating a national platform for other deceased donor intervention trials.

Main Trial Research Question

Does the administration of tacrolimus (vs placebo) to neurologically deceased donors: (i) reduce kidney delayed graft function (DGF) (primary outcome), (ii) reduce DGF in all organs, and (iii) reduce graft loss and recipient death at 1 year; without causing harm?

Study Design

This is a multi-centre, randomized, double-blind, placebo-controlled pilot 2.5 year study that will include 414 participants (90 donors PLUS approximately 324 corresponding recipients).

Intervention

• Experimental arm: a single 4-hour infusion of tacrolimus, 0.02 mg/kg IBW diluted with 0.9% sodium chloride in 250 mL bags.
• Control arm: a single 4-hour infusion of the placebo (0.9% Sodium Chloride)

Outcomes

We will assess feasibility with respect to:  1) donor accrual; and 2) consent rates of organ recipients. Secondarily, we will evaluate the methods for obtaining long-term outcome data. Secondary clinical outcomes related to the main trial include unexpected adverse events, safety outcomes in donors and recipients, graft function within 7 days post transplantation, as well as vital status, re-transplantation and dialysis at 1 year.