- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00248040
Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation
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 Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Montpellier, France, 34295 Cedex 5
- Service de Nephrologie et Transplantation, Hopital Lapeyronie, Centre Hospitalier Universitaire Montpellier
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Paris, France, 75743 Cedex 15
- Service de Transplantation et Soins Intensifs Nephrologiques, Hopital Necker
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Bergamo, Italy, 24128
- Divisione di Nefrologia e Dialisi, Ospedali Riuniti di Bergamo
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Brescia, Italy, 25123
- Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Spedali Civili di Brescia
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Padova, Italy, 35128
- Università degli Studi di Padova, Clinica Chirurgica III
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Barcelona, Spain, 08036
- Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona
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Barcelona, Spain, 08907
- Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Transplant Center, University of Minnesota Medical School
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19102
- Division of Transplantation, Drexel University College of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 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. |
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.
Other Names:
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Experimental: 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. |
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.
Other Names:
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Placebo Comparator: 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.
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placebo was volume/schedule matched saline
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Creatinine Clearance (CrCl) in the Immediate Post-transplant Period
Time Frame: 1-3 and 10-12 hours post allograft reperfusion
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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. |
1-3 and 10-12 hours post allograft reperfusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Renal Function Tests - Serum Creatinine
Time Frame: daily up to day 7 post-transplant or hospital discharge
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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.
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daily up to day 7 post-transplant or hospital discharge
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Renal Function Tests - Calculated Glomerular Filtration Rate
Time Frame: from Day 1 up to 7 days post-transplant or up to hospital discharge
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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
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from Day 1 up to 7 days post-transplant or up to hospital discharge
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Renal Function Tests - Urine Output
Time Frame: from Day 1 up to 7 days post-transplant or up to hospital discharge
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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
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from Day 1 up to 7 days post-transplant or up to hospital discharge
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Number of Patients Requiring Dialysis Within 7 Days Post-transplant
Time Frame: up to day 7 post-transplant
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The number of patients who required dialysis within 7 days post-transplant was evaluated.
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up to day 7 post-transplant
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Number of Days on Dialysis Before Resuming Kidney Function
Time Frame: up to Day 7 post-transplant
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the number of days on dialysis before resuming kidney function was evaluated.
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up to Day 7 post-transplant
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Number of Patients With Immediate, Slow and Delayed Graft Function
Time Frame: day 5 post-transplant
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The number of patients who required dialysis within 7 days post-transplant was evaluated. Immediate graft function: SrCr ≤3 mg/dL on post operative day 5) Slow graft function: SrCr >3 mg/dL dL on post operative day 5, no need of dialysis) Delayed graft function: Dialysis needed in the first week) |
day 5 post-transplant
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Duration of Hospital Stay
Time Frame: first 30 days post-transplant
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The mean duration of hospital stay was evaluated.
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first 30 days post-transplant
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Mortality
Time Frame: first 30 days post-transplant
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Mortality in the first 30 days post-transplant was evaluated.
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first 30 days post-transplant
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Serum Creatinine at Month 1, Month 6 and Month 12
Time Frame: at Month 1, Month 6 and Month 12
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Serum creatinine (SrCr) was measured at Month 1, Month 6 and Month 12.
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at Month 1, Month 6 and Month 12
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Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12
Time Frame: at Month 1, Month 6 and Month 12
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Creatinine clearance (CrCl) is the volume of blood plasma cleared of creatinine per unit time.
It is a rapid and cost-effective method for the measurement of renal function.
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at Month 1, Month 6 and Month 12
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Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12
Time Frame: at Month 6 and between Month 6 and Month 12
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Acute rejection defined as an increase in serum creatinine level after exclusion of other causes of graft dysfunction, accompanied by a sudden decline in glomerular filtration rate and renal function and well-established diagnostic features on kidney allograft biopsy which can be either antibody-mediated and/or T cell-mediated and can occur at any time after transplant.
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at Month 6 and between Month 6 and Month 12
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Patient Survival Rate
Time Frame: at Month 1, Month 6 and Month 12
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Numbers of patients alive, dead, and lost to follow up are reported.
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at Month 1, Month 6 and Month 12
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Graft Survival Rate
Time Frame: at Month 1, Month 6 and Month 12
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Graft failure was defined as the failure of graft function for any reason, ultimately requiring renal replacement therapy and/or retransplantation (United States Renal Data System [USRDS] 2017.
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at Month 1, Month 6 and Month 12
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Giuseppe Remuzzi, MD, A.O. Ospedale Papa Giovanni XXIII
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Urologic Diseases
- Postoperative Complications
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Kidney Diseases
- Ischemia
- Reperfusion Injury
- Delayed Graft Function
Other Study ID Numbers
- REP0204
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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