Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation

Dompé Farmaceutici S.p.A80 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

Conditions

Ischemia-Reperfusion Injury Kidney Diseases

Interventions

Reparixin continuous infusionDRUG

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.

reparixin intermittent infusionDRUG

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 infusionOTHER

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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

Locations (9)

Transplant Center, University of Minnesota Medical School

Minneapolis, Minnesota, United States

Division of Transplantation, Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Service de Nephrologie et Transplantation, Hopital Lapeyronie, Centre Hospitalier Universitaire Montpellier

Montpellier, France

Outcomes

Primary Outcomes

Creatinine Clearance (CrCl) in the Immediate Post-transplant Period

CrCl was determined by two 60 minute urine collections, during the time intervals 1-3 and 10-12 hours of allograft reperfusion. Blood was withdrawn at the midpoint of each urine collection. CrCl at each timepoint was calculated according to the formula: creatinine clearance (mL/minutes) = urine creatinine (mmol/L) x urine volume (mL) / serum creatinine (mmol/L) x time of collection (minutes) An average was to be calculated from the two 60 minute values in each interval.

Time frame: 1-3 and 10-12 hours post allograft reperfusion

Secondary Outcomes

Renal Function Tests - Serum Creatinine

Serum creatinine (SrCr) was measured daily from Day 1 up to 7 days post-transplant or up to hospital discharge, whichever occurred earlier; in patients undergoing dialysis, SrCr values were measured immediately before dialysis.

Time frame: daily up to day 7 post-transplant or hospital discharge

Renal Function Tests - Calculated Glomerular Filtration Rate

Calculated glomerular filtration rate (GFR) was measured daily from Day 1 up to 7 days post-transplant or up to hospital discharge, whichever occurred earlier; in patients undergoing dialysis, SrCr values were measured immediately before dialysis

Time frame: from Day 1 up to 7 days post-transplant or up to hospital discharge

Renal Function Tests - Urine Output

Urine output, measured in the interval from transplant to 8:00 of Day 1, and then daily from Day 2 up to 7 days post-transplant or up to hospital discharge, whichever occurred earlier

Time frame: from Day 1 up to 7 days post-transplant or up to hospital discharge

Number of Patients Requiring Dialysis Within 7 Days Post-transplant

The number of patients who required dialysis within 7 days post-transplant was evaluated.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.