Reparixin in Prevention of Delayed Graft Dysfunction After Kidney Transplantation

Delayed graft function (DGF) is the most common allograft complication in the immediate
kidney post-transplant period, affecting 25-35% of all patients who receive a cadaver graft,
but rates up to 50% have been reported, especially in recipients of kidneys from marginal
donors. It is an important clinical complication as it requires dialysis, prolongs
hospitalisation, raises the cost of transplantation, and makes more difficult the management
of immunosuppressive therapy. Although the effects of DGF on long-term graft function are
still debated, there is overall increasing evidence that DGF reduces long-term graft
survival. Moreover, given the well documented impact of acute rejection on long-term graft
survival, it is conceivable that DGF and acute rejection synergize in negatively influencing
long-term graft survival. Kidney reperfusion, after long cold ischemia period, is associated
with an inflammatory reaction characterized by massive polymorphonuclear leukocyte (PMN)
infiltration both at the glomerular and tubular levels. The importance of CXCL8 in recruiting
PMN in kidney tissue during the ischemic time and after reperfusion has been clearly
documented.

The efficacy of reparixin in preventing PMN infiltration and tissue damage in rat models of
kidney transplantation and lung transplantation, as well as the safety shown in human phase 1
studies, provide the rationale for a clinical study aimed at evaluating the effect of
reparixin in preventing DGF after kidney transplantation

Inclusion Criteria:

- Male and female patients accepted and listed for renal transplantation due to end
stage renal disease (ESRD)

- Planned isolated single kidney transplant from a non-living donor with brain death

- Recipients of a kidney maintained in cold storage

- Recipients at risk of developing DGF

- Planned induction with steroids + mycophenolate mofetil (MMF) or mycophenolic acid +
biological induction

- Patient willing and able to comply with the protocol procedures for the duration of
the study, including scheduled follow-up visits and examinations

- Patient given written informed consent, prior to any study-related procedure not part
of normal medical care, with the understanding that consent may be withdrawn by the
patient at any time without prejudice to their future medical care

Exclusion Criteria:

- Recipients of an intended multiple organ transplant

- Recipients of a kidney from a living donor

- Recipients of a kidney from a non-heart beating donor

- Recipients of double kidney transplant

- Re-transplant >2

- Recipients of a kidney maintained by pulsatile machine perfusion

- Concurrent sepsis

- Recipients with hepatic dysfunction at the time of transplant

- Clinical contraindications to central line access, or arteriovenous fistula, if any,
not suitable for infusion of investigational product

- Hypersensitivity to non steroidal anti-inflammatory drugs (NSAIDs)

- Patients simultaneously participating in any other clinical trials involving an
investigational drug not yet authorized for use in kidney transplant

- Pregnant or breast-feeding women