Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation
Condition: Ischemia-Reperfusion Injury; Kidney Diseases
MeSH terms: Kidney Diseases; Reperfusion Injury; Ischemia; Delayed Graft Function
Study type: Interventional
Phase: Phase 2

Summary: 
      The chemokine CXCL8 plays a key role in the recruitment and activation of polymorphonuclear
      neutrophils in post-ischemia reperfusion injury after solid organ transplantation. Reparixin
      is a novel, specific inhibitor of CXCL8. This study is configured to explore the safety and
      efficacy of reparixin in preventing the delayed graft function (DGF) after kidney
      transplantation.
    

Detailed description: 
      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
    

Intervention name(s): Reparixin continuous infusion; reparixin intermittent infusion; placebo infusion
Intervention type(s): Drug; Drug; Other
Intervention description(s): The Investigational Product was administered as an intravenous infusion into a (high flow) central vein or through an arterio-venous fistula, by an infusion pump adequate to provide reliable infusion rates, as per treatment schedule. Total infusion volume did not exceed 500 mL/24 hours. A dose of 2.772 mg/kg body weight/hour was to be administered for 12 hours. Placebo was volume/schedule matched saline.; A dose of 2.244 mg/kg body weight was to be administered over a 30-minute period, followed by a 1.5-hour interval. Twelve doses were to be administered over a total period of 22.5 hours. Placebo was volume/schedule matched saline.; placebo was volume/schedule matched saline
Other intervention name(s): REP; REP
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Kidney transplantation; Reperfusion Injury; Survival