Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation

NCT ID: NCT00248040

Last Updated: 2024-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-10-31
• Study Completion Date: 2008-06-30

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

Conditions

Ischemia-Reperfusion Injury; Kidney Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

reparixin group - continuous infusion

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.

Group Type: EXPERIMENTAL

Reparixin continuous infusion

Intervention Type: DRUG

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 group - intermittent infusion

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.

Group Type: EXPERIMENTAL

reparixin intermittent infusion

Intervention Type: DRUG

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 infusion

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.

Group Type: PLACEBO_COMPARATOR

placebo infusion

Intervention Type: OTHER

placebo was volume/schedule matched saline

Interventions

Reparixin continuous infusion

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 Type: DRUG

reparixin intermittent infusion

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 Type: DRUG

placebo infusion

placebo was volume/schedule matched saline

Intervention Type: OTHER

Other Intervention Names

REP; REP

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Dompé Farmaceutici S.p.A

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Giuseppe Remuzzi, MD

Role: PRINCIPAL_INVESTIGATOR

A.O. Ospedale Papa Giovanni XXIII

Locations

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

Service de Transplantation et Soins Intensifs Nephrologiques, Hopital Necker

Paris, , France

Divisione di Nefrologia e Dialisi, Ospedali Riuniti di Bergamo

Bergamo, , Italy

Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Spedali Civili di Brescia

Brescia, , Italy

Università degli Studi di Padova, Clinica Chirurgica III

Padua, , Italy

Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona

Barcelona, , Spain

Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge

Barcelona, , Spain

Countries

United States; France; Italy; Spain

Other Identifiers

REP0204

Identifier Type: -

Identifier Source: org_study_id