Kidney Transplantation, Renal Transplantation
Conditions
Keywords
Transplant, Renal transplant, Rejection,allograf, Rejection, Xenograft rejection, Host vs graft disease, Kidney Transplant
Brief summary
This study was designed to evaluate the renal function comparing Certican based immunosuppressive regimens with two different CNIs (Tacrolimus or Cyclosporin A) versus a standard treatment with Mycophenolic Acid and Tacrolimus in de novo renal transplant recipients.
Interventions
DRUGEverolimus
DRUGTacrolimus
Capsules: 0.5 mg, 1 mg or 5 mg. Dosing schedule: transplant to month 2: 4-8ng/ml, month 3 to month 12 3-5 ng/ml according to standard blood levels
DRUGCyclosporin A
Capsules: 10 mg, 25 mg, 50 mg or 100 mg. Transplantation to month 2: 75 - 125 ng/ml, month 3 to month 12: 50 - 100 ng/ml
Tablets: 180 mg or 360 mg. Dosing: duration of study 360 mg bid and no less than 360 mg daily dose
DRUGMycophenolate mofetil (MMF)
Capsules: 250 or 500 mg. Dosing: duration of study 500 mg bid and no less than 500 mg total daily dose
DRUGCorticosteroids
A minimum dose of 5 mg prednisolon or equivalent
DRUGSimulect
Lyophilisate in vials with ampoules of sterile water for injection (5 mL), one vial containing 20 mg lyophilisate given intravenously on the day of transplantation and on day four post-transplantation.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient who had received a primary or secondary kidney transplant * Patients who were willing and from whom written informed consent was obtained * kidney allograft with a cold ischemia time (CIT) \< 30 hours * negative pregnancy test prior to study enrollment
Exclusion criteria
--Multi-organ recipients * former Graft loss due to immunological reasons * Patients who received a kidney from a non-heart beating donor * A-B-0 incompatible transplants * a current Panel Reactive Antibody (PRA) level of \> 20% * existing antibodies against the HLA-type of the receiving transplant * a known hypersensitivity/contraindication to any of the immunosuppressants * Use of other investigational drugs * Patients with thrombocytopenia (platelets \< 100,000/mm³), with an absolute neutrophil count of \< 2,000/mm³ or leucopenia (leucocytes \< 3,000/mm³), or hemoglobin \< 8 g/dL * significant mental illness * history of malignancy during the last five years * HIV positive * uncontrolled hypercholesterolemia or hypertriglyceridemia * drug or alcohol abuse * pregnant or breast feeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | One year post transplant | To demonstrate non-inferiority in renal function assessed by glomerular filtration rate (Nankivell formula) in at least one of the Certican® treatment regimens compared to the standard regimen group at month 12 post-transplantation in renal transplant patients. Nankivell formula: GFR = 6.7/Scr + BW/4 - Surea/2 - 100/(height)² + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The eGFR is expressed in mL/min per 1.73m². If a patient was on dialysis at the time of urea or creatinine assessment, the eGFR was set to 0. Analysis set = per protocol set |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant | Month 12 post transplant | Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method = GFR=141 x min(Scr/κ, 1)α x max(Scr/κ, 1)1.209 x 0.993Age x 1.018 \[if female\] x 1.159 \[if black\] where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is 0.329 for females and 0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model |
| Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant | Month 12 post transplant | Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model |
| Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant | Month 12 post transplant | Modification of Diet in Renal Disease (MDRD) = For men: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x (albumin0,318) For women: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x albumin0,318) x 0.762 with urea nitrogen = urea / 2.144. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model |
| Percentage of Participants With Treatment Failure Endpoints at Month 12 | Month 12 post transplant | Treatment failure endpoints: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS) |
| Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | Month 12 post transplant | Combined endpoint included: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS) |
| Percent of Participants With Delayed Graft Function by Day | Post transplant up to day 7 | Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. |
| Percent of Participants With Viral Infections | Post transplant to month 12 | Viral infections for BKV Virus Humane Polyomavirus 1 and Cytomegalovirus |
| Percent of Participants With Wound Healing Complications During Study | Post transplant until individual reporting | Information collected to report wound healing process which included percentage of participants with complications, fluid collections detected and occurrence of lymphoceles |
| Duration of Wound Healing | Post transplant until individual reporting | A wound will be considered healed if all the suture material and staples are removed and the wound is intact. Number of participants is based on all patients of the respective treatment group in the safety set, excluding patients with no answer (unknown). |
| Percent of Participants With Delayed Graft Function and Slow Graft Function | Post transplant to month 12 | Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. Slow graft function (SGF) was defined as a serum creatinine \>3.0 mg/dL at Day 5 post-transplantation. Full analysis set |
Countries
France, Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TAC+MPA Tacrolimus, Mycophenolic acid (MPA), corticosteroids and Simulect | 205 |
| TAC+Certican Tacrolimus, Certican, corticosteroids and Simulect | 208 |
| CycA+Certican Cyclosporin A, Certican, corticosteroids and Simulect | 199 |
| Total | 612 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 5 | 3 | 4 |
| Overall Study | Graft loss/retransplantation | 5 | 8 | 11 |
| Overall Study | Lost to Follow-up | 5 | 4 | 2 |
| Overall Study | Various reasons | 4 | 9 | 6 |
| Overall Study | Withdrawal by Subject | 4 | 16 | 18 |
Baseline characteristics
| Characteristic | TAC+MPA | TAC+Certican | CycA+Certican | Total |
|---|---|---|---|---|
| Age, Continuous | 55.3 years STANDARD_DEVIATION 12.09 | 54.3 years STANDARD_DEVIATION 13.5 | 55.1 years STANDARD_DEVIATION 12.61 | 54.9 years STANDARD_DEVIATION 12.74 |
| Sex: Female, Male Female | 65 Participants | 70 Participants | 66 Participants | 201 Participants |
| Sex: Female, Male Male | 140 Participants | 138 Participants | 133 Participants | 411 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 200 / 204 | 205 / 210 | 196 / 198 |
| serious Total, serious adverse events | 135 / 204 | 161 / 210 | 144 / 198 |
Outcome results
Primary
Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens
To demonstrate non-inferiority in renal function assessed by glomerular filtration rate (Nankivell formula) in at least one of the Certican® treatment regimens compared to the standard regimen group at month 12 post-transplantation in renal transplant patients. Nankivell formula: GFR = 6.7/Scr + BW/4 - Surea/2 - 100/(height)² + C where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The eGFR is expressed in mL/min per 1.73m². If a patient was on dialysis at the time of urea or creatinine assessment, the eGFR was set to 0. Analysis set = per protocol set
Time frame: One year post transplant
Population: Protocol analysis set comprised of participants who received at least one dose of study drug without major protocol deviaitons
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| TAC+MPA | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 9 - Day 229 to 319 (140,106,77) | 69.47 mL/min per 1.73m² | Standard Deviation 16.251 |
| TAC+MPA | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 6 - Day 137 to 228 (142,108,76) | 68.05 mL/min per 1.73m² | Standard Deviation 16.994 |
| TAC+MPA | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 1 - Day 1 to 60 (146,111,78) | 62.62 mL/min per 1.73m² | Standard Deviation 16.931 |
| TAC+MPA | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 3 - Day 61 to 136 (143,108,79) | 66.36 mL/min per 1.73m² | Standard Deviation 16.672 |
| TAC+MPA | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month12 - Day 320 to 450 (147,111, 80) | 70.41 mL/min per 1.73m² | Standard Deviation 16.514 |
| TAC+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 6 - Day 137 to 228 (142,108,76) | 62.76 mL/min per 1.73m² | Standard Deviation 16.763 |
| TAC+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 1 - Day 1 to 60 (146,111,78) | 60.54 mL/min per 1.73m² | Standard Deviation 17.31 |
| TAC+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 3 - Day 61 to 136 (143,108,79) | 61.21 mL/min per 1.73m² | Standard Deviation 14.771 |
| TAC+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 9 - Day 229 to 319 (140,106,77) | 64.68 mL/min per 1.73m² | Standard Deviation 15.507 |
| TAC+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month12 - Day 320 to 450 (147,111, 80) | 63.34 mL/min per 1.73m² | Standard Deviation 16.986 |
| CycA+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month12 - Day 320 to 450 (147,111, 80) | 61.51 mL/min per 1.73m² | Standard Deviation 16.942 |
| CycA+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 9 - Day 229 to 319 (140,106,77) | 62.89 mL/min per 1.73m² | Standard Deviation 14.947 |
| CycA+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 1 - Day 1 to 60 (146,111,78) | 59.47 mL/min per 1.73m² | Standard Deviation 16.754 |
| CycA+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 6 - Day 137 to 228 (142,108,76) | 63.17 mL/min per 1.73m² | Standard Deviation 16.789 |
| CycA+Certican | Glomular Filtration Rate (GFR) mL/Min Via Nankivell Method at Month 12 - Standard Regimen vs Certican Regimens | Month 3 - Day 61 to 136 (143,108,79) | 62.22 mL/min per 1.73m² | Standard Deviation 16.196 |
Comparison: The trial tests the null hypotheses that the treatment difference (investigational minus reference) in mean eGFR at re-assigned visit Month 12 is lower than the non-inferiority margin (Δ) of 7 mL/min per 1.73m2 versus the alternative that the treatment difference is equal to or greater than the non-inferiority marginp-value: <0.000195% CI: [-13.82, -4.88]ANOVA
p-value: 0.006795% CI: [-9.56, -1.55]ANOVA
Secondary
Duration of Wound Healing
A wound will be considered healed if all the suture material and staples are removed and the wound is intact. Number of participants is based on all patients of the respective treatment group in the safety set, excluding patients with no answer (unknown).
Time frame: Post transplant until individual reporting
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAC+MPA | Duration of Wound Healing | 42.4 days | Standard Deviation 41.13 |
| TAC+Certican | Duration of Wound Healing | 54.1 days | Standard Deviation 61.97 |
| CycA+Certican | Duration of Wound Healing | 85.3 days | Standard Deviation 62.7 |
Secondary
Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant
Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
Time frame: Month 12 post transplant
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TAC+MPA | Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant | 60.26 mL/min per 1.73m² |
| TAC+Certican | Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant | 52.25 mL/min per 1.73m² |
| CycA+Certican | Glomular Filtration Rate (GFR) mL/Min Via Cockcroft- Gault Method at Month 12 Post Transplant | 51.30 mL/min per 1.73m² |
Secondary
Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method = GFR=141 x min(Scr/κ, 1)α x max(Scr/κ, 1)1.209 x 0.993Age x 1.018 \[if female\] x 1.159 \[if black\] where Scr is serum creatinine, κ is 0.7 for females and 0.9 for males, α is 0.329 for females and 0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
Time frame: Month 12 post transplant
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TAC+MPA | Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant | 51.62 mL/min per 1.73m² |
| TAC+Certican | Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant | 44.42 mL/min per 1.73m² |
| CycA+Certican | Glomular Filtration Rate (GFR) Via Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Method at Month 12 Post Transplant | 42.44 mL/min per 1.73m² |
Secondary
Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant
Modification of Diet in Renal Disease (MDRD) = For men: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x (albumin0,318) For women: GFR = 170 x (serum creatinine -0,999) x (age-0,176) x (urea nitrogen -0,17) x albumin0,318) x 0.762 with urea nitrogen = urea / 2.144. last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
Time frame: Month 12 post transplant
Population: Full analysis set
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| TAC+MPA | Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant | 53.24 mL/min per 1.73m² |
| TAC+Certican | Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant | 45.72 mL/min per 1.73m² |
| CycA+Certican | Glomular Filtration Rate (GFR) Via Modification of Diet in Renal Disease (MDRD) Method at Month 12 Post Transplant | 43.47 mL/min per 1.73m² |
Secondary
Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12
Combined endpoint included: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS)
Time frame: Month 12 post transplant
Population: Full analysis set includes all participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAC+MPA | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR or graft loss or death | 9.8 Percentage of participants |
| TAC+MPA | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR, graft loss, death, or loss of follow-up | 15.6 Percentage of participants |
| TAC+Certican | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR or graft loss or death | 13.0 Percentage of participants |
| TAC+Certican | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR, graft loss, death, or loss of follow-up | 22.6 Percentage of participants |
| CycA+Certican | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR or graft loss or death | 24.6 Percentage of participants |
| CycA+Certican | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR, graft loss, death, or loss of follow-up | 32.7 Percentage of participants |
| Tac+Certican - Tac+MPA - Difference Between Groups | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR, graft loss, death, or loss of follow-up | 7.0 Percentage of participants |
| Tac+Certican - Tac+MPA - Difference Between Groups | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR or graft loss or death | 3.2 Percentage of participants |
| CycA+Certican -Tac+MPA - Difference Between Groups | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR or graft loss or death | 14.9 Percentage of participants |
| CycA+Certican -Tac+MPA - Difference Between Groups | Percentage of Participants With Composite Treatment Failure Endpoints - Difference Between Groups at Month 12 | BPAR, graft loss, death, or loss of follow-up | 17.1 Percentage of participants |
Comparison: TAC+Certican - TAC+MPA - difference between groups95% CI: [-0.029, 0.093]
Comparison: CycA+Certican -Tac+MPA - difference between groups95% CI: [0.076, 0.221]
Secondary
Percentage of Participants With Treatment Failure Endpoints at Month 12
Treatment failure endpoints: biopsy proven acute rejection (BPAR) defined as a rejection which was acute and proven by biopsy, graft loss (GL) defined as: allograft was presumed to be lost on the day the patient starts dialysis and not able to be removed from dialysis or death. Patients who prematurely discontinued the study: if the patient did not suffer from an event before discontinuation and reason was not related to efficacy, the patient was assessed as having had no event, otherwise the patient was assessed as having had an event. Full analysis set (FAS)
Time frame: Month 12 post transplant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAC+MPA | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Biopsy proven acute rejection (BPAR) | 9.3 Percentage of participants |
| TAC+MPA | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Treated BPAR (tBPAR) | 8.8 Percentage of participants |
| TAC+MPA | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Graft loss | 5.4 Percentage of participants |
| TAC+MPA | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Death | 4.9 Percentage of participants |
| TAC+Certican | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Death | 6.3 Percentage of participants |
| TAC+Certican | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Biopsy proven acute rejection (BPAR) | 12.0 Percentage of participants |
| TAC+Certican | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Graft loss | 6.3 Percentage of participants |
| TAC+Certican | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Treated BPAR (tBPAR) | 11.5 Percentage of participants |
| CycA+Certican | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Death | 6.5 Percentage of participants |
| CycA+Certican | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Treated BPAR (tBPAR) | 23.6 Percentage of participants |
| CycA+Certican | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Graft loss | 9.0 Percentage of participants |
| CycA+Certican | Percentage of Participants With Treatment Failure Endpoints at Month 12 | Biopsy proven acute rejection (BPAR) | 24.6 Percentage of participants |
Comparison: BPAR - treatment differences at Month 12p-value: <0.00195% CI: [-0.032, 0.087]Pearson's chi-square test
Secondary
Percent of Participants With Delayed Graft Function and Slow Graft Function
Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day. Slow graft function (SGF) was defined as a serum creatinine \>3.0 mg/dL at Day 5 post-transplantation. Full analysis set
Time frame: Post transplant to month 12
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAC+MPA | Percent of Participants With Delayed Graft Function and Slow Graft Function | Delayed graft function (197,187,172) | 17.8 Percent of participants |
| TAC+MPA | Percent of Participants With Delayed Graft Function and Slow Graft Function | Slow graft function (195,187,171) | 46.2 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function and Slow Graft Function | Delayed graft function (197,187,172) | 20.3 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function and Slow Graft Function | Slow graft function (195,187,171) | 48.7 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function and Slow Graft Function | Delayed graft function (197,187,172) | 22.1 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function and Slow Graft Function | Slow graft function (195,187,171) | 49.7 Percent of participants |
Secondary
Percent of Participants With Delayed Graft Function by Day
Delayed graft function (DGF) was defined as the need for dialysis within the first 7 days post-transplantation, excluding the first post-transplantation day.
Time frame: Post transplant up to day 7
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAC+MPA | Percent of Participants With Delayed Graft Function by Day | day 3 (5,1,2) | 14.3 Percent of participants |
| TAC+MPA | Percent of Participants With Delayed Graft Function by Day | day 1 (8,7,4) | 22.9 Percent of participants |
| TAC+MPA | Percent of Participants With Delayed Graft Function by Day | day 2 (2,2,2) | 5.7 Percent of participants |
| TAC+MPA | Percent of Participants With Delayed Graft Function by Day | day 4 (4,2,4) | 11.4 Percent of participants |
| TAC+MPA | Percent of Participants With Delayed Graft Function by Day | day 5 (4,5,3) | 11.4 Percent of participants |
| TAC+MPA | Percent of Participants With Delayed Graft Function by Day | day 6 (1,1,2) | 2.9 Percent of participants |
| TAC+MPA | Percent of Participants With Delayed Graft Function by Day | day 7 (2,4,0) | 5.7 Percent of participants |
| TAC+MPA | Percent of Participants With Delayed Graft Function by Day | >7 days (9,16,21) | 25.7 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function by Day | day 3 (5,1,2) | 2.6 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function by Day | day 7 (2,4,0) | 10.5 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function by Day | day 4 (4,2,4) | 5.3 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function by Day | day 5 (4,5,3) | 13.2 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function by Day | day 6 (1,1,2) | 2.6 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function by Day | day 1 (8,7,4) | 18.4 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function by Day | >7 days (9,16,21) | 42.1 Percent of participants |
| TAC+Certican | Percent of Participants With Delayed Graft Function by Day | day 2 (2,2,2) | 5.3 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function by Day | day 2 (2,2,2) | 5.3 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function by Day | day 6 (1,1,2) | 5.3 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function by Day | day 3 (5,1,2) | 5.3 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function by Day | day 4 (4,2,4) | 10.5 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function by Day | day 7 (2,4,0) | 0.0 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function by Day | day 1 (8,7,4) | 10.5 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function by Day | day 5 (4,5,3) | 7.9 Percent of participants |
| CycA+Certican | Percent of Participants With Delayed Graft Function by Day | >7 days (9,16,21) | 55.3 Percent of participants |
Secondary
Percent of Participants With Viral Infections
Viral infections for BKV Virus Humane Polyomavirus 1 and Cytomegalovirus
Time frame: Post transplant to month 12
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - CMVModerate | 6.0 Percent of participants |
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - BKVSevere | 0 Percent of participants |
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - BKVAsymptomatic | 10.0 Percent of participants |
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - CMVSevere | 1.0 Percent of participants |
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - CMVMissing | 1.0 Percent of participants |
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - BKVModerate | 7.0 Percent of participants |
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - CMVMild | 5.0 Percent of participants |
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - CMVAsymptomatic | 7.0 Percent of participants |
| TAC+MPA | Percent of Participants With Viral Infections | Viral infections - BKVMild | 5.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - CMVSevere | 0.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - CMVMissing | 0.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - CMVAsymptomatic | 1.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - CMVMild | 2.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - CMVModerate | 1.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - BKVAsymptomatic | 8.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - BKVMild | 7.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - BKVModerate | 2.0 Percent of participants |
| TAC+Certican | Percent of Participants With Viral Infections | Viral infections - BKVSevere | 0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - CMVMild | 1.0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - CMVMissing | 1.0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - BKVMild | 3.0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - CMVAsymptomatic | 1.0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - BKVSevere | 0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - CMVSevere | 0.0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - CMVModerate | 1.0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - BKVModerate | 1.0 Percent of participants |
| CycA+Certican | Percent of Participants With Viral Infections | Viral infections - BKVAsymptomatic | 5.0 Percent of participants |
Secondary
Percent of Participants With Wound Healing Complications During Study
Information collected to report wound healing process which included percentage of participants with complications, fluid collections detected and occurrence of lymphoceles
Time frame: Post transplant until individual reporting
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TAC+MPA | Percent of Participants With Wound Healing Complications During Study | Fluids detected | 18.7 Percent of participants |
| TAC+MPA | Percent of Participants With Wound Healing Complications During Study | Occurrence of lymphoceles | 11.8 Percent of participants |
| TAC+MPA | Percent of Participants With Wound Healing Complications During Study | Wound healing complication | 14.3 Percent of participants |
| TAC+Certican | Percent of Participants With Wound Healing Complications During Study | Fluids detected | 26.8 Percent of participants |
| TAC+Certican | Percent of Participants With Wound Healing Complications During Study | Wound healing complication | 19.1 Percent of participants |
| TAC+Certican | Percent of Participants With Wound Healing Complications During Study | Occurrence of lymphoceles | 18.2 Percent of participants |
| CycA+Certican | Percent of Participants With Wound Healing Complications During Study | Wound healing complication | 22.2 Percent of participants |
| CycA+Certican | Percent of Participants With Wound Healing Complications During Study | Occurrence of lymphoceles | 21.8 Percent of participants |
| CycA+Certican | Percent of Participants With Wound Healing Complications During Study | Fluids detected | 27.8 Percent of participants |