Clinical trial NCT00248040
Conditions: Ischemia-Reperfusion Injury Kidney Diseases
Keywords: Kidney transplantation Reperfusion Injury Survival
Sponsor: Dompé Farmaceutici S.p.A
Start date: 2005-10-01; Completion date: 2008-06-01
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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

Arms: arm 1: Continuous iv infusion into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump.

A dose of 2.772 mg/kg/h was administered for12 hours. arm 2: Intermittent iv infusion into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump.

A dose of 2.244 mg/kg was administered over a 30-minute period, followed by a 1.5-hour interval. Twelve doses were administered over a total period of 22.5 hours. arm 3: Continuous/intermittent iv infusion of a volume/schedule matched saline into a (high flow) central vein (or through an arterio-venous fistula) by an infusion pump.
Interventions: intervention 1: Reparixin continuous infusion intervention 2: reparixin intermittent infusion intervention 3: placebo infusion
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: placebo was volume/schedule matched saline

Protocol documents: