Reparixin in Prevention of Delayed Graft Dysfunction After Kidney Transplantation

This study has been completed.
Sponsor:
Information provided by:
Dompé s.p.a.
ClinicalTrials.gov Identifier:
NCT00248040
First received: November 2, 2005
Last updated: June 7, 2011
Last verified: June 2011
  Purpose

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 Intervention Phase
Ischemia-Reperfusion Injury
Kidney Diseases
Drug: Reparixin continuous infusion
Drug: reparixin intermittent infusion
Other: placebo infusion
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Dompé s.p.a.:

Primary Outcome Measures:
  • Creatinine clearance (CrCl) in the immediate post-transplant period [ Time Frame: 1-3 and 10-12 hours post-reperfusion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Renal function tests [ Time Frame: daily up to day 7 post-transplant ] [ Designated as safety issue: No ]
  • Number of patients requiring dialysis within 7 days post-transplant [ Time Frame: up to day 7 post-transplant ] [ Designated as safety issue: No ]
  • Number of patients with immediate, slow and delayed graft function [ Time Frame: day 5 post-transplant ] [ Designated as safety issue: No ]
  • Acute rejection episodes [ Time Frame: month 6 and 12 post-transplant ] [ Designated as safety issue: No ]
  • Patient and graft survival rate [ Time Frame: month 6 and 12 post-transplant ] [ Designated as safety issue: No ]
  • Pharmacokinetic profile [ Time Frame: day 1 and 2 of treatment ] [ Designated as safety issue: No ]
  • Standard laboratory tests and vital signs [ Time Frame: day -1 pre-transplant and day 7 post-transplant ] [ Designated as safety issue: Yes ]

Enrollment: 80
Study Start Date: October 2005
Study Completion Date: June 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00248040

Locations
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
France
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
Italy
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
Spain
Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge
Barcelona, Spain, 08907
Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Sponsors and Collaborators
Dompé s.p.a.
  More Information

No publications provided

Responsible Party: Dr. Marcello Allegretti/Research and Development Director, Dompé s.p.a.
ClinicalTrials.gov Identifier: NCT00248040     History of Changes
Other Study ID Numbers: REP0204
Study First Received: November 2, 2005
Last Updated: June 7, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Dompé s.p.a.:
Kidney transplantation
Reperfusion Injury
Survival

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

ClinicalTrials.gov processed this record on September 18, 2014