Ischemia-Reperfusion InjuryPhase 2NCT00248040
Reparixin in Prevention of Delayed Graft Function After Kidney Transplantation
A Phase 2 study testing Reparixin continuous infusion and reparixin intermittent infusion in people with Ischemia-Reperfusion Injury and Kidney Diseases, run by Dompé Farmaceutici S.p.A at 9 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Ischemia-Reperfusion Injury, Kidney Diseases
- What is being tested?
- Reparixin continuous infusion and reparixin intermittent infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 9 sitesin 4 countries
- Study dates
- Oct 2005to Jun 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
Italy3 sites
Divisione di Nefrologia e Dialisi, Ospedali Riuniti di Bergamo
Bergamo, 24128
Divisione di Nefrologia e Dialisi, Azienda Ospedaliera Spedali Civili di Brescia
Brescia, 25123
Università degli Studi di Padova, Clinica Chirurgica III
Padova, 35128
United States2 sites
Transplant Center, University of Minnesota Medical School
Minneapolis, Minnesota, 55455
Division of Transplantation, Drexel University College of Medicine
Philadelphia, Pennsylvania, 19102
France2 sites
Service de Nephrologie et Transplantation, Hopital Lapeyronie, Centre Hospitalier Universitaire Montpellier
Montpellier, 34295 Cedex 5
Service de Transplantation et Soins Intensifs Nephrologiques, Hopital Necker
Paris, 75743 Cedex 15
Spain2 sites
Renal Transplant Unit, Hopital Clinic i Provincial de Barcelona
Barcelona, 08036
Division of Nephrology, Institut Catala de la Salut, Ciutat Sanitaria i Universitaria de Bellvitge
Barcelona, 08907
About this study
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
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.
Read the 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
- Conditions
- Ischemia-Reperfusion Injury, Kidney Diseases
- Being tested
- Reparixin continuous infusion, reparixin intermittent infusion, placebo infusion
- Keywords
- Kidney transplantation, Reperfusion Injury, Survival
- Medical subject headings
- Reperfusion Injury, Kidney Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Reparixin continuous infusionDrug
Also called REP
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.
reparixin intermittent infusionDrug
Also called REP
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.
placebo infusionOther
placebo was volume/schedule matched saline
| Study group | Role | What they receive |
|---|---|---|
| reparixin group - continuous infusion | Experimental | 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. Receives: Drug: Reparixin continuous infusion |
| reparixin group - intermittent infusion | Experimental | 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. Receives: Drug: reparixin intermittent infusion |
| placebo infusion | Placebo comparator | 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. Receives: Other: placebo infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1-3 and 10-12 hours post allograft reperfusion
Secondary outcomes (13)
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.
Measured: daily up to day 7 post-transplant or hospital discharge
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
Measured: from Day 1 up to 7 days post-transplant or up to hospital discharge
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
Measured: from Day 1 up to 7 days post-transplant or up to hospital discharge
Number of Patients Requiring Dialysis Within 7 Days Post-transplant
The number of patients who required dialysis within 7 days post-transplant was evaluated.
Measured: up to day 7 post-transplant
Number of Days on Dialysis Before Resuming Kidney Function
the number of days on dialysis before resuming kidney function was evaluated.
Measured: up to Day 7 post-transplant
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)
Measured: day 5 post-transplant
Duration of Hospital Stay
The mean duration of hospital stay was evaluated.
Measured: first 30 days post-transplant
Mortality
Mortality in the first 30 days post-transplant was evaluated.
Measured: first 30 days post-transplant
Serum Creatinine at Month 1, Month 6 and Month 12
Serum creatinine (SrCr) was measured at Month 1, Month 6 and Month 12.
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.
Measured: at Month 1, Month 6 and Month 12
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.
Measured: at Month 6 and between Month 6 and Month 12
Patient Survival Rate
Numbers of patients alive, dead, and lost to follow up are reported.
Measured: at Month 1, Month 6 and Month 12
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.
Measured: at Month 1, Month 6 and Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2005 (estimated)
- Study startOct 2005
- Primary completionMay 2008
- Study completionJun 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Ischemia-Reperfusion InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dompé Farmaceutici S.p.A
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Giuseppe Remuzzi, MD, Principal investigator, A.O. Ospedale Papa Giovanni XXIII
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00248040
- Sponsor's protocol ID
- REP0204
- Status last verified
- Sep 2020
- First submitted
- 2 Nov 2005
- Last updated
- 10 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00248040
- Acronym / sponsor ID
- REP0204
- Conditions
- Ischemia-Reperfusion Injury, Kidney Diseases
- Keywords
- Kidney transplantation, Reperfusion Injury, Survival
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Dompé Farmaceutici S.p.AIndustry (pharma, biotech, devices)
- Study start
- Oct 2005 (actual)
- Primary completion
- May 2008 (actual)
- Study completion
- Jun 2008 (actual)
- First posted
- 3 Nov 2005 (estimated)
- Results
- Posted 14 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| reparixin group - continuous infusion | Experimental | Drug: Reparixin continuous infusionContinuous 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. |
| reparixin group - intermittent infusion | Experimental | Drug: reparixin intermittent infusionIntermittent 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. |
| placebo infusion | Placebo comparator | Other: placebo infusionContinuous/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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Reparixin continuous infusionAlso: REPThe 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. | Drug | reparixin group - continuous infusion |
| reparixin intermittent infusionAlso: REPA 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. | Drug | reparixin group - intermittent infusion |
| placebo infusionplacebo was volume/schedule matched saline | Other | placebo infusion |
Primary outcome
Creatinine Clearance (CrCl) in the Immediate Post-transplant Period
Time frame: 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.
13 secondary outcomes
Renal Function Tests - Serum Creatinine
Time frame: daily up to day 7 post-transplant or hospital discharge
Renal Function Tests - Calculated Glomerular Filtration Rate
Time frame: from Day 1 up to 7 days post-transplant or up to hospital discharge
Renal Function Tests - Urine Output
Time frame: from Day 1 up to 7 days post-transplant or up to hospital discharge
Number of Patients Requiring Dialysis Within 7 Days Post-transplant
Time frame: up to day 7 post-transplant
Number of Days on Dialysis Before Resuming Kidney Function
Time frame: up to Day 7 post-transplant
Number of Patients With Immediate, Slow and Delayed Graft Function
Time frame: day 5 post-transplant
Duration of Hospital Stay
Time frame: first 30 days post-transplant
Mortality
Time frame: first 30 days post-transplant
Serum Creatinine at Month 1, Month 6 and Month 12
Time frame: at Month 1, Month 6 and Month 12
Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12
Time frame: at Month 1, Month 6 and Month 12
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
Patient Survival Rate
Time frame: at Month 1, Month 6 and Month 12
Graft Survival Rate
Time frame: at Month 1, Month 6 and Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuseppe Remuzzi, MD principal investigator
A.O. Ospedale Papa Giovanni XXIII
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Reparixin continuous infusion and reparixin intermittent infusion in people with Ischemia-Reperfusion Injury and Kidney Diseases, run by Dompé Farmaceutici S.p.A at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Italy, United States, France, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Creatinine Clearance (CrCl) in the Immediate Post-transplant Period (time frame: 1-3 and 10-12 hours post allograft reperfusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2024.