Ischemia-Reperfusion Injury, Kidney Diseases
Conditions
Keywords
Kidney transplantation, Reperfusion Injury, Survival
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
Interventions
DRUGReparixin continuous infusion
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.
DRUGreparixin intermittent infusion
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.
OTHERplacebo infusion
placebo was volume/schedule matched saline
Sponsors
Dompé Farmaceutici S.p.A
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Patient Survival Rate | at Month 1, Month 6 and Month 12 | Numbers of patients alive, dead, and lost to follow up are reported. |
| 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 |
| 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. |
| 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) |
| 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. |
| 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. |
| 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. |
| Duration of Hospital Stay | first 30 days post-transplant | The mean duration of hospital stay was evaluated. |
Countries
France, Italy, Spain, United States
Participant flow
Recruitment details
74 pt. (25 & 23 in reparixin continuous and intermittent infusion, and 26 in the pooled placebo) received the drug and were included in the safety population; 73 pt. (24, 23, 26) received both the study drug and the transplant and were included in the ITT. 1 started study drug but did not receive a kidney transplant, so was excluded from the ITT.
Pre-assignment details
Six patients (2 in the reparixin continuous infusion group; 3 in the reparixin intermittent infusion group; 1 in the placebo intermittent infusion group) did not receive Investigational Product(s) or kidney transplants and hence they were excluded from both the Safety and ITT populations.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 25 |
| 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. | 23 |
| Placebo Continuous/Intermittent 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. | 26 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | transplant cancelled post treat start | 1 | 0 | 0 |
| Overall Study | transplantectomy | 2 | 1 | 3 |
Baseline characteristics
| Characteristic | Placebo Continuous/Intermittent Infusion | Total | Reparixin Continuous Infusion | Reparixin Intermittent Infusion |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 26 Participants | 74 Participants | 25 Participants | 23 Participants |
| Age, Continuous | 51.4 years STANDARD_DEVIATION 11.3 | 53.8 years STANDARD_DEVIATION 8.8 | 54.4 years STANDARD_DEVIATION 7.4 | 55.9 years STANDARD_DEVIATION 6.3 |
| Region of Enrollment France | 10 participants | 29 participants | 10 participants | 9 participants |
| Region of Enrollment Italy | 8 participants | 21 participants | 6 participants | 7 participants |
| Region of Enrollment Spain | 4 participants | 16 participants | 7 participants | 5 participants |
| Region of Enrollment United States | 4 participants | 8 participants | 2 participants | 2 participants |
| Sex: Female, Male Female | 19 Participants | 50 Participants | 18 Participants | 13 Participants |
| Sex: Female, Male Male | 7 Participants | 24 Participants | 7 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 23 | 1 / 26 |
| other Total, other adverse events | 24 / 25 | 23 / 23 | 25 / 26 |
| serious Total, serious adverse events | 12 / 25 | 5 / 23 | 9 / 26 |
Outcome results
Primary
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.
Time frame: 1-3 and 10-12 hours post allograft reperfusion
Population: ITT population. The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin Continuous Infusion | Creatinine Clearance (CrCl) in the Immediate Post-transplant Period | 1-3 hours post-transplant | 5.11 mL/min | Standard Deviation 8.56 |
| Reparixin Continuous Infusion | Creatinine Clearance (CrCl) in the Immediate Post-transplant Period | 10-12 hours post-transplant | 9.66 mL/min | Standard Deviation 10.52 |
| Reparixin Intermittent Infusion | Creatinine Clearance (CrCl) in the Immediate Post-transplant Period | 1-3 hours post-transplant | 7.44 mL/min | Standard Deviation 12.81 |
| Reparixin Intermittent Infusion | Creatinine Clearance (CrCl) in the Immediate Post-transplant Period | 10-12 hours post-transplant | 14.45 mL/min | Standard Deviation 17.39 |
| Placebo Continuous/Intermittent Infusion | Creatinine Clearance (CrCl) in the Immediate Post-transplant Period | 1-3 hours post-transplant | 6.30 mL/min | Standard Deviation 6.26 |
| Placebo Continuous/Intermittent Infusion | Creatinine Clearance (CrCl) in the Immediate Post-transplant Period | 10-12 hours post-transplant | 10.75 mL/min | Standard Deviation 10.93 |
Comparison: This analysis refers to the 1-3 hours time pointp-value: 0.907695% CI: [-5, 4.45]Other
Comparison: This analysis refers to the 1-3 hours timepoint.p-value: 0.308495% CI: [-2.32, 7.21]Other
p-value: 0.256595% CI: [-7.47, 2.03]Other
Comparison: This analysis refers to the 10-12 hours time point.p-value: 0.985595% CI: [-6.91, 6.79]Other
Comparison: This analysis refers to the 10-12 hours timepoint.p-value: 0.193495% CI: [-2.36, 11.39]Other
Comparison: This analysis refers to the 10-12 hours time point.p-value: 0.179795% CI: [-11.3, 2.17]Other
Secondary
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.
Time frame: at Month 6 and between Month 6 and Month 12
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin Continuous Infusion | Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12 | Month 6 | 2 episodes |
| Reparixin Continuous Infusion | Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12 | Between Month 6 and Month 12 | 0 episodes |
| Reparixin Intermittent Infusion | Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12 | Month 6 | 6 episodes |
| Reparixin Intermittent Infusion | Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12 | Between Month 6 and Month 12 | 0 episodes |
| Placebo Continuous/Intermittent Infusion | Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12 | Month 6 | 2 episodes |
| Placebo Continuous/Intermittent Infusion | Acute Rejection Episodes at Month 6 and Between Month 6 and Month 12 | Between Month 6 and Month 12 | 4 episodes |
Secondary
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.
Time frame: at Month 1, Month 6 and Month 12
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin Continuous Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 12 | 53.48 mL/min | Standard Deviation 20.39 |
| Reparixin Continuous Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 6 | 52.43 mL/min | Standard Deviation 18.18 |
| Reparixin Continuous Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 1 | 42.86 mL/min | Standard Deviation 22.56 |
| Reparixin Intermittent Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 6 | 51.14 mL/min | Standard Deviation 12.54 |
| Reparixin Intermittent Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 1 | 44.75 mL/min | Standard Deviation 16.2 |
| Reparixin Intermittent Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 12 | 51.10 mL/min | Standard Deviation 15.07 |
| Placebo Continuous/Intermittent Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 1 | 41.21 mL/min | Standard Deviation 14.23 |
| Placebo Continuous/Intermittent Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 12 | 41.74 mL/min | Standard Deviation 19.03 |
| Placebo Continuous/Intermittent Infusion | Calculated Serum Creatinine Clearance at Month 1, Month 6 and Month 12 | Month 6 | 46.93 mL/min | Standard Deviation 16.65 |
Secondary
Duration of Hospital Stay
The mean duration of hospital stay was evaluated.
Time frame: first 30 days post-transplant
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reparixin Continuous Infusion | Duration of Hospital Stay | 14.6 days | Standard Deviation 8.4 |
| Reparixin Intermittent Infusion | Duration of Hospital Stay | 16.1 days | Standard Deviation 7.6 |
| Placebo Continuous/Intermittent Infusion | Duration of Hospital Stay | 13.3 days | Standard Deviation 7.9 |
Secondary
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.
Time frame: at Month 1, Month 6 and Month 12
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin Continuous Infusion | Graft Survival Rate | Month 1 - Graft functioning | 21 number of grafts |
| Reparixin Continuous Infusion | Graft Survival Rate | Month 1 - Graft failed | 3 number of grafts |
| Reparixin Continuous Infusion | Graft Survival Rate | Month 6 - Graft functioning | 19 number of grafts |
| Reparixin Continuous Infusion | Graft Survival Rate | Month 6 - Graft failed | 0 number of grafts |
| Reparixin Continuous Infusion | Graft Survival Rate | Month 12 - Graft functioning | 18 number of grafts |
| Reparixin Continuous Infusion | Graft Survival Rate | Month 12 - Graft failed | 1 number of grafts |
| Reparixin Intermittent Infusion | Graft Survival Rate | Month 12 - Graft failed | 1 number of grafts |
| Reparixin Intermittent Infusion | Graft Survival Rate | Month 1 - Graft functioning | 22 number of grafts |
| Reparixin Intermittent Infusion | Graft Survival Rate | Month 6 - Graft failed | 0 number of grafts |
| Reparixin Intermittent Infusion | Graft Survival Rate | Month 12 - Graft functioning | 20 number of grafts |
| Reparixin Intermittent Infusion | Graft Survival Rate | Month 1 - Graft failed | 1 number of grafts |
| Reparixin Intermittent Infusion | Graft Survival Rate | Month 6 - Graft functioning | 22 number of grafts |
| Placebo Continuous/Intermittent Infusion | Graft Survival Rate | Month 1 - Graft failed | 3 number of grafts |
| Placebo Continuous/Intermittent Infusion | Graft Survival Rate | Month 6 - Graft functioning | 20 number of grafts |
| Placebo Continuous/Intermittent Infusion | Graft Survival Rate | Month 12 - Graft failed | 0 number of grafts |
| Placebo Continuous/Intermittent Infusion | Graft Survival Rate | Month 6 - Graft failed | 1 number of grafts |
| Placebo Continuous/Intermittent Infusion | Graft Survival Rate | Month 1 - Graft functioning | 22 number of grafts |
| Placebo Continuous/Intermittent Infusion | Graft Survival Rate | Month 12 - Graft functioning | 20 number of grafts |
Secondary
Mortality
Mortality in the first 30 days post-transplant was evaluated.
Time frame: first 30 days post-transplant
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reparixin Continuous Infusion | Mortality | No | 24 Participants |
| Reparixin Continuous Infusion | Mortality | Yes | 0 Participants |
| Reparixin Intermittent Infusion | Mortality | No | 23 Participants |
| Reparixin Intermittent Infusion | Mortality | Yes | 0 Participants |
| Placebo Continuous/Intermittent Infusion | Mortality | No | 25 Participants |
| Placebo Continuous/Intermittent Infusion | Mortality | Yes | 1 Participants |
Secondary
Number of Days on Dialysis Before Resuming Kidney Function
the number of days on dialysis before resuming kidney function was evaluated.
Time frame: up to Day 7 post-transplant
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reparixin Continuous Infusion | Number of Days on Dialysis Before Resuming Kidney Function | 2.5 days | Standard Deviation 0.7 |
| Reparixin Intermittent Infusion | Number of Days on Dialysis Before Resuming Kidney Function | 1.0 days | Standard Deviation 0 |
| Placebo Continuous/Intermittent Infusion | Number of Days on Dialysis Before Resuming Kidney Function | 2.0 days | Standard Deviation 0 |
Secondary
Number of Patients Requiring Dialysis Within 7 Days Post-transplant
The number of patients who required dialysis within 7 days post-transplant was evaluated.
Time frame: up to day 7 post-transplant
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reparixin Continuous Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | No | 15 Participants |
| Reparixin Continuous Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | Yes | 7 Participants |
| Reparixin Continuous Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | Unknown | 2 Participants |
| Reparixin Intermittent Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | No | 15 Participants |
| Reparixin Intermittent Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | Yes | 7 Participants |
| Reparixin Intermittent Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | Unknown | 1 Participants |
| Placebo Continuous/Intermittent Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | Yes | 6 Participants |
| Placebo Continuous/Intermittent Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | Unknown | 2 Participants |
| Placebo Continuous/Intermittent Infusion | Number of Patients Requiring Dialysis Within 7 Days Post-transplant | No | 18 Participants |
Secondary
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)
Time frame: day 5 post-transplant
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reparixin Continuous Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Immediate graft function | 6 Participants |
| Reparixin Continuous Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Slow graft function | 8 Participants |
| Reparixin Continuous Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Delayed graft function | 8 Participants |
| Reparixin Continuous Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Unknown | 2 Participants |
| Reparixin Intermittent Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Unknown | 0 Participants |
| Reparixin Intermittent Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Immediate graft function | 10 Participants |
| Reparixin Intermittent Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Delayed graft function | 8 Participants |
| Reparixin Intermittent Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Slow graft function | 5 Participants |
| Placebo Continuous/Intermittent Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Unknown | 2 Participants |
| Placebo Continuous/Intermittent Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Slow graft function | 11 Participants |
| Placebo Continuous/Intermittent Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Delayed graft function | 6 Participants |
| Placebo Continuous/Intermittent Infusion | Number of Patients With Immediate, Slow and Delayed Graft Function | Immediate graft function | 7 Participants |
Secondary
Patient Survival Rate
Numbers of patients alive, dead, and lost to follow up are reported.
Time frame: at Month 1, Month 6 and Month 12
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reparixin Continuous Infusion | Patient Survival Rate | Month 12 - Alive | 19 Participants |
| Reparixin Continuous Infusion | Patient Survival Rate | Month 12 - Dead | 0 Participants |
| Reparixin Continuous Infusion | Patient Survival Rate | Month 1 - Dead | 0 Participants |
| Reparixin Continuous Infusion | Patient Survival Rate | Month 12 - Lost to follow up | 1 Participants |
| Reparixin Continuous Infusion | Patient Survival Rate | Month 6 - Dead | 0 Participants |
| Reparixin Continuous Infusion | Patient Survival Rate | Month 1 - Lost to follow up | 2 Participants |
| Reparixin Continuous Infusion | Patient Survival Rate | Month 1 - Alive | 22 Participants |
| Reparixin Continuous Infusion | Patient Survival Rate | Month 6 - Alive | 20 Participants |
| Reparixin Continuous Infusion | Patient Survival Rate | Month 6 - Lost to follow up | 2 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 6 - Lost to follow up | 0 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 12 - Alive | 21 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 6 - Dead | 0 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 6 - Alive | 22 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 12 - Dead | 1 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 1 - Lost to follow up | 1 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 1 - Alive | 22 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 12 - Lost to follow up | 0 Participants |
| Reparixin Intermittent Infusion | Patient Survival Rate | Month 1 - Dead | 0 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 12 - Lost to follow up | 0 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 6 - Dead | 0 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 1 - Alive | 22 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 1 - Dead | 1 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 1 - Lost to follow up | 3 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 6 - Lost to follow up | 1 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 12 - Alive | 21 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 12 - Dead | 0 Participants |
| Placebo Continuous/Intermittent Infusion | Patient Survival Rate | Month 6 - Alive | 21 Participants |
Secondary
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
Time frame: from Day 1 up to 7 days post-transplant or up to hospital discharge
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin Continuous Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 2 | 6.95 mL/min | Standard Deviation 5 |
| Reparixin Continuous Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 5 | 17.97 mL/min | Standard Deviation 22.53 |
| Reparixin Continuous Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 4 | 13.90 mL/min | Standard Deviation 15.15 |
| Reparixin Continuous Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 1 | 6.04 mL/min | Standard Deviation 2.99 |
| Reparixin Continuous Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 7 | 22.42 mL/min | Standard Deviation 22.35 |
| Reparixin Continuous Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 6 | 20.46 mL/min | Standard Deviation 24.24 |
| Reparixin Continuous Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 3 | 10.99 mL/min | Standard Deviation 12.26 |
| Reparixin Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 4 | 19.64 mL/min | Standard Deviation 15.28 |
| Reparixin Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 1 | 8.03 mL/min | Standard Deviation 6.46 |
| Reparixin Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 2 | 10.68 mL/min | Standard Deviation 8.61 |
| Reparixin Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 3 | 14.86 mL/min | Standard Deviation 11.67 |
| Reparixin Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 5 | 23.91 mL/min | Standard Deviation 19.02 |
| Reparixin Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 6 | 26.64 mL/min | Standard Deviation 19.81 |
| Reparixin Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 7 | 28.06 mL/min | Standard Deviation 20.1 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 5 | 18.61 mL/min | Standard Deviation 22.03 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 2 | 8.74 mL/min | Standard Deviation 8.06 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 7 | 22.70 mL/min | Standard Deviation 24.45 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 6 | 20.75 mL/min | Standard Deviation 24.01 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 4 | 15.79 mL/min | Standard Deviation 18.57 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 3 | 13.15 mL/min | Standard Deviation 15.22 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Calculated Glomerular Filtration Rate | Day 1 | 7.03 mL/min | Standard Deviation 3.48 |
Secondary
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.
Time frame: daily up to day 7 post-transplant or hospital discharge
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin Continuous Infusion | Renal Function Tests - Serum Creatinine | Day 2 | 0.683 mmol/L | Standard Deviation 0.244 |
| Reparixin Continuous Infusion | Renal Function Tests - Serum Creatinine | Day 5 | 0.509 mmol/L | Standard Deviation 0.281 |
| Reparixin Continuous Infusion | Renal Function Tests - Serum Creatinine | Day 4 | 0.589 mmol/L | Standard Deviation 0.33 |
| Reparixin Continuous Infusion | Renal Function Tests - Serum Creatinine | Day 1 | 0.686 mmol/L | Standard Deviation 0.178 |
| Reparixin Continuous Infusion | Renal Function Tests - Serum Creatinine | Day 7 | 0.474 mmol/L | Standard Deviation 0.351 |
| Reparixin Continuous Infusion | Renal Function Tests - Serum Creatinine | Day 6 | 0.510 mmol/L | Standard Deviation 0.334 |
| Reparixin Continuous Infusion | Renal Function Tests - Serum Creatinine | 0.Day 3 | 0.632 mmol/L | Standard Deviation 0.311 |
| Reparixin Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 4 | 0.427 mmol/L | Standard Deviation 0.26 |
| Reparixin Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 1 | 0.643 mmol/L | Standard Deviation 0.219 |
| Reparixin Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 2 | 0.576 mmol/L | Standard Deviation 0.254 |
| Reparixin Intermittent Infusion | Renal Function Tests - Serum Creatinine | 0.Day 3 | 0.500 mmol/L | Standard Deviation 0.27 |
| Reparixin Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 5 | 0.383 mmol/L | Standard Deviation 0.253 |
| Reparixin Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 6 | 0.333 mmol/L | Standard Deviation 0.206 |
| Reparixin Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 7 | 0.318 mmol/L | Standard Deviation 0.212 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 5 | 0.567 mmol/L | Standard Deviation 0.367 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 2 | 0.658 mmol/L | Standard Deviation 0.278 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 7 | 0.542 mmol/L | Standard Deviation 0.411 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 6 | 0.570 mmol/L | Standard Deviation 0.407 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 4 | 0.601 mmol/L | Standard Deviation 0.36 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Serum Creatinine | 0.Day 3 | 0.613 mmol/L | Standard Deviation 0.317 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Serum Creatinine | Day 1 | 0.651 mmol/L | Standard Deviation 0.202 |
Secondary
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
Time frame: from Day 1 up to 7 days post-transplant or up to hospital discharge
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin Continuous Infusion | Renal Function Tests - Urine Output | Day 4 | 2409.8 mL | Standard Deviation 2043.2 |
| Reparixin Continuous Infusion | Renal Function Tests - Urine Output | Day 6 | 1795.8 mL | Standard Deviation 1206.2 |
| Reparixin Continuous Infusion | Renal Function Tests - Urine Output | Day 7 | 2072.3 mL | Standard Deviation 1240.9 |
| Reparixin Continuous Infusion | Renal Function Tests - Urine Output | Day 5 | 1958.2 mL | Standard Deviation 1609.2 |
| Reparixin Continuous Infusion | Renal Function Tests - Urine Output | Day 2 | 2242.7 mL | Standard Deviation 2236.8 |
| Reparixin Continuous Infusion | Renal Function Tests - Urine Output | Day 3 | 2321.1 mL | Standard Deviation 2087.8 |
| Reparixin Continuous Infusion | Renal Function Tests - Urine Output | Day 1 | 1615.9 mL | Standard Deviation 2082.7 |
| Reparixin Intermittent Infusion | Renal Function Tests - Urine Output | Day 4 | 2583.3 mL | Standard Deviation 1698.6 |
| Reparixin Intermittent Infusion | Renal Function Tests - Urine Output | Day 3 | 2979.6 mL | Standard Deviation 2000.1 |
| Reparixin Intermittent Infusion | Renal Function Tests - Urine Output | Day 6 | 2239.3 mL | Standard Deviation 1228.1 |
| Reparixin Intermittent Infusion | Renal Function Tests - Urine Output | Day 1 | 1749.9 mL | Standard Deviation 2109.9 |
| Reparixin Intermittent Infusion | Renal Function Tests - Urine Output | Day 2 | 2620.2 mL | Standard Deviation 2444.1 |
| Reparixin Intermittent Infusion | Renal Function Tests - Urine Output | Day 7 | 2226.1 mL | Standard Deviation 1093.2 |
| Reparixin Intermittent Infusion | Renal Function Tests - Urine Output | Day 5 | 2474.8 mL | Standard Deviation 1575.4 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Urine Output | Day 7 | 1805.1 mL | Standard Deviation 1390.9 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Urine Output | Day 5 | 2035.4 mL | Standard Deviation 1816.7 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Urine Output | Day 4 | 2939.4 mL | Standard Deviation 2585 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Urine Output | Day 1 | 1925.3 mL | Standard Deviation 2214.1 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Urine Output | Day 2 | 2844.5 mL | Standard Deviation 2861.2 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Urine Output | Day 3 | 2904.0 mL | Standard Deviation 2468.3 |
| Placebo Continuous/Intermittent Infusion | Renal Function Tests - Urine Output | Day 6 | 1994.8 mL | Standard Deviation 1688.5 |
Secondary
Serum Creatinine at Month 1, Month 6 and Month 12
Serum creatinine (SrCr) was measured at Month 1, Month 6 and Month 12.
Time frame: at Month 1, Month 6 and Month 12
Population: The ITT population consisted of all randomized patients who received any Investigational Product(s) and a kidney transplant.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin Continuous Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 6 | 0.145 mmo/L | Standard Deviation 0.0658 |
| Reparixin Continuous Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 1 | 0.252 mmo/L | Standard Deviation 0.225 |
| Reparixin Continuous Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 12 | 0.150 mmo/L | Standard Deviation 0.0879 |
| Reparixin Intermittent Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 6 | 0.139 mmo/L | Standard Deviation 0.0417 |
| Reparixin Intermittent Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 1 | 0.169 mmo/L | Standard Deviation 0.0777 |
| Reparixin Intermittent Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 12 | 0.150 mmo/L | Standard Deviation 0.0618 |
| Placebo Continuous/Intermittent Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 1 | 0.186 mmo/L | Standard Deviation 0.089 |
| Placebo Continuous/Intermittent Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 12 | 0.227 mmo/L | Standard Deviation 0.2578 |
| Placebo Continuous/Intermittent Infusion | Serum Creatinine at Month 1, Month 6 and Month 12 | Month 6 | 0.179 mmo/L | Standard Deviation 0.1227 |