Clinical trial NCT00248040: Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation
Official title: Randomized, Double-blind, Placebo-controlled, Parallel-group Pilot Study to Assess Efficacy, Safety and Pharmacokinetics of 2 Schedules of Reparixin in the Prevention of Delayed Graft Function After Kidney Transplant in High Risk Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ischemia-Reperfusion Injury
Kidney Diseases
Keywords: Kidney transplantation
Reperfusion Injury
Survival
Lead sponsor: Dompé Farmaceutici S.p.A
Sponsor class: INDUSTRY
First posted: 2005-11-03
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility criteria: 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

Primary outcomes:
measure: Creatinine Clearance (CrCl) in the Immediate Post-transplant Period
timeFrame: 1-3 and 10-12 hours post allograft reperfusion
Secondary outcomes:
measure: Renal Function Tests - Serum Creatinine
timeFrame: daily up to day 7 post-transplant or hospital discharge
measure: Renal Function Tests - Calculated Glomerular Filtration Rate
timeFrame: from Day 1 up to 7 days post-transplant or up to hospital discharge
measure: Renal Function Tests - Urine Output
timeFrame: from Day 1 up to 7 days post-transplant or up to hospital discharge
measure: Number of Patients Requiring Dialysis Within 7 Days Post-transplant
timeFrame: up to day 7 post-transplant
measure: Number of Days on Dialysis Before Resuming Kidney Function
timeFrame: up to Day 7 post-transplant
measure: Number of Patients With Immediate, Slow and Delayed Graft Function
timeFrame: day 5 post-transplant
measure: Duration of Hospital Stay
timeFrame: first 30 days post-transplant
measure: Mortality
timeFrame: first 30 days post-transplant
measure: Serum Creatinine at Month 1, Month 6 and Month 12
timeFrame: at Month 1, Month 6 and Month 12
measure: Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12
timeFrame: at Month 1, Month 6 and Month 12
measure: Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12
timeFrame: at Month 6 and between Month 6 and Month 12
measure: Patient Survival Rate
timeFrame: at Month 1, Month 6 and Month 12
measure: Graft Survival Rate
timeFrame: at Month 1, Month 6 and Month 12
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Transplant Center, University of Minnesota Medical School
state: Minnesota
city: Philadelphia
country: United States
facility: Division of Transplantation, Drexel University College of Medicine
state: Pennsylvania
city: Montpellier
country: France
facility: Service de Nephrologie et Transplantation, Hopital Lapeyronie, Centre Hospitalier Universitaire Montpellier
city: Paris
country: France
facility: Service de Transplantation et Soins Intensifs Nephrologiques, Hopital Necker
city: Bergamo
country: Italy
facility: Divisione di Nefrologia e Dialisi, Ospedali Riuniti di Bergamo
city: Brescia
country: Italy
facility: Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Spedali Civili di Brescia
city: Padova
country: Italy
facility: Università degli Studi di Padova, Clinica Chirurgica III
city: Barcelona
country: Spain
facility: Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge
Study officials:
affiliation: A.O. Ospedale Papa Giovanni XXIII
name: Giuseppe Remuzzi, MD
role: PRINCIPAL_INVESTIGATOR
References: