Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation
- Conditions
- Kidney DiseasesIschemia-Reperfusion Injury
- Interventions
- Registration Number
- NCT00248040
- Lead Sponsor
- 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.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description reparixin group - intermittent infusion reparixin 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. reparixin group - continuous infusion Reparixin 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. placebo infusion 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.
- Primary Outcome Measures
Name Time Method Creatinine Clearance (CrCl) in the Immediate Post-transplant Period 1-3 and 10-12 hours post allograft reperfusion 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.
- Secondary Outcome Measures
Name Time Method Number of Patients Requiring Dialysis Within 7 Days Post-transplant up to day 7 post-transplant The number of patients who required dialysis within 7 days post-transplant was evaluated.
Renal Function Tests - Serum Creatinine daily up to day 7 post-transplant or hospital discharge 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.
Renal Function Tests - Calculated Glomerular Filtration Rate from Day 1 up to 7 days post-transplant or up to hospital discharge 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
Renal Function Tests - Urine Output from Day 1 up to 7 days post-transplant or up to hospital discharge 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
Duration of Hospital Stay first 30 days post-transplant The mean duration of hospital stay was evaluated.
Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12 at Month 6 and between Month 6 and Month 12 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.
Graft Survival Rate at Month 1, Month 6 and Month 12 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.
Number of Days on Dialysis Before Resuming Kidney Function up to Day 7 post-transplant the number of days on dialysis before resuming kidney function was evaluated.
Number of Patients With Immediate, Slow and Delayed Graft Function day 5 post-transplant 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)Mortality first 30 days post-transplant Mortality in the first 30 days post-transplant was evaluated.
Serum Creatinine at Month 1, Month 6 and Month 12 at Month 1, Month 6 and Month 12 Serum creatinine (SrCr) was measured at Month 1, Month 6 and Month 12.
Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 at Month 1, Month 6 and Month 12 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.
Patient Survival Rate at Month 1, Month 6 and Month 12 Numbers of patients alive, dead, and lost to follow up are reported.
Trial Locations
- Locations (9)
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
🇮🇹Padova, 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
Transplant Center, University of Minnesota Medical School🇺🇸Minneapolis, Minnesota, United States