Reparixin in Prevention of Delayed Graft Dysfunction After Kidney Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00248040
Recruitment Status : Completed
First Posted : November 3, 2005
Last Update Posted : June 8, 2011
Information provided by:
Dompé Farmaceutici S.p.A

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.

Condition or disease Intervention/treatment Phase
Ischemia-Reperfusion Injury Kidney Diseases Drug: Reparixin continuous infusion Drug: reparixin intermittent infusion Other: placebo infusion Phase 2

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 2, Multi-centre, Randomized, Double-blind, Placebo-controlled, Parallel-group (3 Arms) Pilot Study to Assess the Efficacy, the Safety and the Pharmacokinetics of Two Treatment Schedules of Reparixin in the Prevention of Delayed Graft Function After Kidney Transplantation in High Risk Patients
Study Start Date : October 2005
Actual Primary Completion Date : May 2008
Actual Study Completion Date : June 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: reparixin continuous infusion Drug: Reparixin continuous infusion
Reparixin continuous infusion

Experimental: reparixin intermittent infusion Drug: reparixin intermittent infusion
reparixin intermittent infusion

Placebo Comparator: placebo infusion Other: placebo infusion
placebo infusion

Primary Outcome Measures :
  1. Creatinine clearance (CrCl) in the immediate post-transplant period [ Time Frame: 1-3 and 10-12 hours post-reperfusion ]

Secondary Outcome Measures :
  1. Renal function tests [ Time Frame: daily up to day 7 post-transplant ]
  2. Number of patients requiring dialysis within 7 days post-transplant [ Time Frame: up to day 7 post-transplant ]
  3. Number of patients with immediate, slow and delayed graft function [ Time Frame: day 5 post-transplant ]
  4. Acute rejection episodes [ Time Frame: month 6 and 12 post-transplant ]
  5. Patient and graft survival rate [ Time Frame: month 6 and 12 post-transplant ]
  6. Pharmacokinetic profile [ Time Frame: day 1 and 2 of treatment ]
  7. Standard laboratory tests and vital signs [ Time Frame: day -1 pre-transplant and day 7 post-transplant ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00248040

United States, Minnesota
Transplant Center, University of Minnesota Medical School
Minneapolis, Minnesota, United States, 55455
United States, Pennsylvania
Division of Transplantation, Drexel University College of Medicine
Philadelphia, Pennsylvania, United States, 19102
Service de Nephrologie et Transplantation, Hopital Lapeyronie, Centre Hospitalier Universitaire Montpellier
Montpellier, France, 34295 Cedex 5
Service de Transplantation et Soins Intensifs Nephrologiques, Hopital Necker
Paris, France, 75743 Cedex 15
Divisione di Nefrologia e Dialisi, Ospedali Riuniti di Bergamo
Bergamo, Italy, 24128
Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Spedali Civili di Brescia
Brescia, Italy, 25123
Università degli Studi di Padova, Clinica Chirurgica III
Padova, Italy, 35128
Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge
Barcelona, Spain, 08907
Sponsors and Collaborators
Dompé Farmaceutici S.p.A

Responsible Party: Dr. Marcello Allegretti/Research and Development Director, Dompé s.p.a. Identifier: NCT00248040     History of Changes
Other Study ID Numbers: REP0204
First Posted: November 3, 2005    Key Record Dates
Last Update Posted: June 8, 2011
Last Verified: June 2011

Keywords provided by Dompé Farmaceutici S.p.A:
Kidney transplantation
Reperfusion Injury

Additional relevant MeSH terms:
Kidney Diseases
Reperfusion Injury
Urologic Diseases
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases
Postoperative Complications