search
Back to results

Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation

Primary Purpose

Ischemia-Reperfusion Injury, Kidney Diseases

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Reparixin continuous infusion
reparixin intermittent infusion
placebo infusion
Sponsored by
Dompé Farmaceutici S.p.A
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ischemia-Reperfusion Injury focused on measuring Kidney transplantation, Reperfusion Injury, Survival

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care Exclusion Criteria: Recipients of an intended multiple organ transplant Recipients of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

Sites / Locations

  • Transplant Center, University of Minnesota Medical School
  • Division of Transplantation, Drexel University College of Medicine
  • Service de Nephrologie et Transplantation, Hopital Lapeyronie, Centre Hospitalier Universitaire Montpellier
  • Service de Transplantation et Soins Intensifs Nephrologiques, Hopital Necker
  • Divisione di Nefrologia e Dialisi, Ospedali Riuniti di Bergamo
  • Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Spedali Civili di Brescia
  • Università degli Studi di Padova, Clinica Chirurgica III
  • Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona
  • Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

reparixin group - continuous infusion

reparixin group - intermittent infusion

placebo infusion

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Creatinine Clearance (CrCl) in the Immediate Post-transplant Period
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

Renal Function Tests - Serum Creatinine
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
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
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
Number of Patients Requiring Dialysis Within 7 Days Post-transplant
The number of patients who required dialysis within 7 days post-transplant was evaluated.
Number of Days on Dialysis Before Resuming Kidney Function
the number of days on dialysis before resuming kidney function was evaluated.
Number of Patients With Immediate, Slow and Delayed Graft Function
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)
Duration of Hospital Stay
The mean duration of hospital stay was evaluated.
Mortality
Mortality in the first 30 days post-transplant was evaluated.
Serum Creatinine 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
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.
Acute Rejection Episodes 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.
Patient Survival Rate
Numbers of patients alive, dead, and lost to follow up are reported.
Graft Survival Rate
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.

Full Information

First Posted
November 2, 2005
Last Updated
September 1, 2020
Sponsor
Dompé Farmaceutici S.p.A
search

1. Study Identification

Unique Protocol Identification Number
NCT00248040
Brief Title
Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
October 2005 (Actual)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
June 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dompé Farmaceutici S.p.A

4. Oversight

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemia-Reperfusion Injury, Kidney Diseases
Keywords
Kidney transplantation, Reperfusion Injury, Survival

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Actual)

8. Arms, Groups, and Interventions

Arm Title
reparixin group - continuous infusion
Arm Type
Experimental
Arm Description
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.
Arm Title
reparixin group - intermittent infusion
Arm Type
Experimental
Arm Description
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.
Arm Title
placebo infusion
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Reparixin continuous infusion
Other Intervention Name(s)
REP
Intervention Description
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
Intervention Name(s)
reparixin intermittent infusion
Other Intervention Name(s)
REP
Intervention Description
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
Other
Intervention Name(s)
placebo infusion
Intervention Description
placebo was volume/schedule matched saline
Primary Outcome Measure Information:
Title
Creatinine Clearance (CrCl) in the Immediate Post-transplant Period
Description
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.
Time Frame
1-3 and 10-12 hours post allograft reperfusion
Secondary Outcome Measure Information:
Title
Renal Function Tests - Serum Creatinine
Description
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.
Time Frame
daily up to day 7 post-transplant or hospital discharge
Title
Renal Function Tests - Calculated Glomerular Filtration Rate
Description
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
Time Frame
from Day 1 up to 7 days post-transplant or up to hospital discharge
Title
Renal Function Tests - Urine Output
Description
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
Time Frame
from Day 1 up to 7 days post-transplant or up to hospital discharge
Title
Number of Patients Requiring Dialysis Within 7 Days Post-transplant
Description
The number of patients who required dialysis within 7 days post-transplant was evaluated.
Time Frame
up to day 7 post-transplant
Title
Number of Days on Dialysis Before Resuming Kidney Function
Description
the number of days on dialysis before resuming kidney function was evaluated.
Time Frame
up to Day 7 post-transplant
Title
Number of Patients With Immediate, Slow and Delayed Graft Function
Description
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)
Time Frame
day 5 post-transplant
Title
Duration of Hospital Stay
Description
The mean duration of hospital stay was evaluated.
Time Frame
first 30 days post-transplant
Title
Mortality
Description
Mortality in the first 30 days post-transplant was evaluated.
Time Frame
first 30 days post-transplant
Title
Serum Creatinine at Month 1, Month 6 and Month 12
Description
Serum creatinine (SrCr) was measured at Month 1, Month 6 and Month 12.
Time Frame
at Month 1, Month 6 and Month 12
Title
Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12
Description
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.
Time Frame
at Month 1, Month 6 and Month 12
Title
Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12
Description
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.
Time Frame
at Month 6 and between Month 6 and Month 12
Title
Patient Survival Rate
Description
Numbers of patients alive, dead, and lost to follow up are reported.
Time Frame
at Month 1, Month 6 and Month 12
Title
Graft Survival Rate
Description
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.
Time Frame
at Month 1, Month 6 and Month 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giuseppe Remuzzi, MD
Organizational Affiliation
A.O. Ospedale Papa Giovanni XXIII
Official's Role
Principal Investigator
Facility Information:
Facility Name
Transplant Center, University of Minnesota Medical School
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Division of Transplantation, Drexel University College of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19102
Country
United States
Facility Name
Service de Nephrologie et Transplantation, Hopital Lapeyronie, Centre Hospitalier Universitaire Montpellier
City
Montpellier
ZIP/Postal Code
34295 Cedex 5
Country
France
Facility Name
Service de Transplantation et Soins Intensifs Nephrologiques, Hopital Necker
City
Paris
ZIP/Postal Code
75743 Cedex 15
Country
France
Facility Name
Divisione di Nefrologia e Dialisi, Ospedali Riuniti di Bergamo
City
Bergamo
ZIP/Postal Code
24128
Country
Italy
Facility Name
Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Spedali Civili di Brescia
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Università degli Studi di Padova, Clinica Chirurgica III
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge
City
Barcelona
ZIP/Postal Code
08907
Country
Spain

12. IPD Sharing Statement

Learn more about this trial

Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation

We'll reach out to this number within 24 hrs