Kidney Transplantation
Conditions
Keywords
de novo renal allograft recipients, renal allograft function, CNI-free regimen
Brief summary
The purpose of this study was to determine whether an early Calcineurin Inhibitor (CNI) to everolimus conversion at 10-14 weeks post transplantation improves renal allograft function without compromising efficacy compared to standard CNI treatment in de novo renal allograft recipients. In addition, the study was designed to evaluate the impact of a CNI-free regimen on evolution of cardiovascular parameters in de novo renal allograft recipients
Detailed description
This was a 24-month, multi-center, randomized, open-label trial with two parallel arms in adult de novo renal allograft recipients. The study consisted of a run-in period from transplantation to Randomization and a treatment period from Randomization until Month 24. At baseline visit, patients were transplanted and entered the run-in period from transplantation (Baseline) to Randomization (week 10-14 post-transplantation). At Week 10-14, eligible patients were randomized into one of the 2 treatment arms: standard CNIs and Myfortic versus everolimus and Myfortic and entered the treatment period of the study from Randomization to Month 24. Patients in both arms received steroids as per center practice and in any caseat least 5 mg/Day. At Randomization, patients were stratified according to their renal allograft function and previous cardiovascular events. The main analysis was performed at Month 12 and the follow-up analysis was performed at Month 24.
Interventions
DRUGEverolimus
Early CNI to everolimus conversion
DRUGPrograf or Neoral
Active CNI-based control (Prograf or Neoral)
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
at Baseline: * Male or female renal allograft recipients at least 18 years old. * Written informed consent. * Patient receiving a primary or secondary kidney transplant from a cadaveric or living unrelated-/related donor. * Cold ischemia time (CIT) \< 24 hours. * Negative pregnancy test for female patients. Inclusion Criteria at Randomization: * Patients on CNI (TAC or CsA) + Myfortic + steroids. * Serum creatinine \< 2.8 mg/dL (250 µmol/L) and an actual eGFR (MDRD4) ≥ 25 mL/min/1.73m exp2 (without renal replacement therapy).
Exclusion criteria
at Baseline: Patients fulfilling any of the following criteria are not eligible for inclusion in this study: * Recipient of multiple organ transplants. * Recipient of ABO incompatible allograft or a positive cross-match. * Panel Reactive Antibodies (PRA) level ≥ 30 %. * Positive test for human immunodeficiency virus (HIV). * Patient receiving an allograft from a Hepatitis B surface Antigen (HBsAg) or a Hepatitis C Virus (HCV) positive donor. * HBsAg and/or a HCV positive patient with evidence of elevated LFTs (ALT/AST levels ≥ 2.5 times ULN). * Severe restrictive or obstructive pulmonary disorders. * Patient with severe allergy requiring acute or chronic treatment or hypersensitivity to any of the study drugs or similar drugs. * Severe hypercholesterolemia or hypertriglyceridemia. * Low platelet count. * Low white blood cell count. * History of malignancy of any organ system
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Glomerular Filtration Rate (eGFR) | Month 12 | Assessment of renal function by comparing change from randomization to Month 12 in eGFR (MDRD4) between treatment arms (Full analysis set). Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR \[mL/min/1.73m˄2\] = 186.3\*(C˄-1.154)\*(A˄-0.203)\*G\*R. DEFINITIONS: C = serum concentration of creatinine \[mg/dL\]; A = age \[years\]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 | at 12 months and month 24 post-transplantation | Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)\*, (2) graft loss\*\*, or (3) death . \*A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. \*\*Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted. |
| Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Randomization, Month 12 and Month 24 | Evolution of left ventricular mass and hypertrophy were evaluated by left ventricular mass index (LVMi) assessed by echocardiography. LVMi is derived using a standard formula from dimensional measurements on the echocardiogram. Analysis of covariance was applied with treatment, center (as a random effect), and donor type as factors and LVMi at Randomization as covariate. |
| Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | at 24 months post-transplantation | (treated BPAR ≥ IB, graft loss or death)A comparison of the incidence rates for the individual components of the composite efficacy endpoint between treatment arms |
Countries
Argentina, Australia, Austria, Belgium, Estonia, France, Germany, Greece, India, Italy, Latvia, Lithuania, Mexico, Netherlands, Norway, Portugal, Romania, Russia, Spain, Thailand, Turkey (Türkiye)
Participant flow
Recruitment details
Full analysis set (24 month analysis)
Participants by arm
| Arm | Count |
|---|---|
| Everolimus Conversion from Calcineurin inhibitor (CNI) to everolimus in combination with Myfortic (mycophenolic acid) and steroids | 353 |
| Standard CNI (Tac) Calcineurin inhibitor (CNI) continuation with Tacrolimus (Tac) in combination with Myfortic (mycophenolic acid), and steroids | 231 |
| Standard CNI (CsA) Calcineurin inhibitor (CNI) continuation with Cyclosporine (CsA) in combination with Myfortic (mycophenolic acid) and steroids | 125 |
| Total | 709 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Completed Study Medication at Month 24 | Abnormal laboratory value(s) | 6 | 0 | 1 |
| Completed Study Medication at Month 24 | Abnormal test procedure result(s) | 3 | 0 | 1 |
| Completed Study Medication at Month 24 | Administrative problems | 2 | 1 | 2 |
| Completed Study Medication at Month 24 | Adverse Event | 87 | 18 | 17 |
| Completed Study Medication at Month 24 | Death | 2 | 1 | 2 |
| Completed Study Medication at Month 24 | Graft loss | 0 | 2 | 0 |
| Completed Study Medication at Month 24 | Lack of Efficacy | 2 | 1 | 2 |
| Completed Study Medication at Month 24 | Lost to Follow-up | 1 | 4 | 2 |
| Completed Study Medication at Month 24 | Missing | 2 | 0 | 0 |
| Completed Study Medication at Month 24 | Protocol Violation | 0 | 5 | 2 |
| Completed Study Medication at Month 24 | Subject's no longer required drug | 1 | 1 | 1 |
| Completed Study Medication at Month 24 | Withdrawal by Subject | 18 | 8 | 2 |
| Completed Study Phase at Month 24 | Death | 8 | 5 | 4 |
| Completed Study Phase at Month 24 | Lost to Follow-up | 10 | 5 | 7 |
| Completed Study Phase at Month 24 | Missing | 2 | 0 | 0 |
| Completed Study Phase at Month 24 | Other | 2 | 0 | 0 |
| Completed Study Phase at Month 24 | Withdrawal by Subject | 18 | 6 | 3 |
Baseline characteristics
| Characteristic | Everolimus | Standard CNI (Tac) | Standard CNI (CsA) | Total |
|---|---|---|---|---|
| Age, Continuous | 46.0 years STANDARD_DEVIATION 14.4 | 47.3 years STANDARD_DEVIATION 14.5 | 45.4 years STANDARD_DEVIATION 15.6 | 46.2 years STANDARD_DEVIATION 14.8 |
| Race/Ethnicity, Customized Asian | 66 participants 18.7 | 41 participants 17.7 | 20 participants 16 | 127 participants |
| Race/Ethnicity, Customized Black | 4 participants 1.1 | 5 participants 2.2 | 0 participants 0 | 9 participants |
| Race/Ethnicity, Customized Caucasian | 246 participants 69.7 | 173 participants 74.9 | 97 participants 77.6 | 516 participants |
| Race/Ethnicity, Customized Native American | 1 participants 0.3 | 0 participants 0 | 0 participants 0 | 1 participants |
| Race/Ethnicity, Customized Other | 36 participants 10.2 | 11 participants 4.8 | 7 participants 5.6 | 54 participants |
| Race/Ethnicity, Customized Pacific Islander | 0 participants 0 | 1 participants 0.4 | 1 participants 0.8 | 2 participants |
| Sex: Female, Male Female | 111 Participants | 71 Participants | 33 Participants | 215 Participants |
| Sex: Female, Male Male | 242 Participants | 160 Participants | 92 Participants | 494 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 | 316 / 346 | 216 / 238 | 103 / 121 |
| serious Total, serious adverse events | 188 / 346 | 118 / 238 | 58 / 121 |
Outcome results
Primary
Estimated Glomerular Filtration Rate (eGFR)
Assessment of renal function by comparing change from randomization to Month 12 in eGFR (MDRD4) between treatment arms (Full analysis set). Renal function was assessed by estimated Glomerular Filtration Rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula. MDRD formula: GFR \[mL/min/1.73m˄2\] = 186.3\*(C˄-1.154)\*(A˄-0.203)\*G\*R. DEFINITIONS: C = serum concentration of creatinine \[mg/dL\]; A = age \[years\]; G = 0.742 when gender is female, otherwise G = 1; R = 1.21 when race is black, otherwise R = 1
Time frame: Month 12
Population: Full Analysis set - observed eGFR values at month 12 (counted the patients with available values)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Everolimus | Estimated Glomerular Filtration Rate (eGFR) | 64.1 mL/min/1.73m^2 | Standard Deviation 22.31 |
| Standard CNI (Tac) | Estimated Glomerular Filtration Rate (eGFR) | 61.5 mL/min/1.73m^2 | Standard Deviation 19.86 |
| Standard CNI (CsA) | Estimated Glomerular Filtration Rate (eGFR) | 58.4 mL/min/1.73m^2 | Standard Deviation 19.62 |
Secondary
Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24
Evolution of left ventricular mass and hypertrophy were evaluated by left ventricular mass index (LVMi) assessed by echocardiography. LVMi is derived using a standard formula from dimensional measurements on the echocardiogram. Analysis of covariance was applied with treatment, center (as a random effect), and donor type as factors and LVMi at Randomization as covariate.
Time frame: Randomization, Month 12 and Month 24
Population: Full Analysis Set consists of only patients with triple LVMi values available at randomization, Month 12 and month 24 are included
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Everolimus | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Month 12 | 49.95 g/m^2.7 | Standard Deviation 12.63 |
| Everolimus | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Randomization | 50.30 g/m^2.7 | Standard Deviation 11.62 |
| Everolimus | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Month 24 | 46.66 g/m^2.7 | Standard Deviation 12.19 |
| Standard CNI (Tac) | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Month 12 | 48.98 g/m^2.7 | Standard Deviation 14.63 |
| Standard CNI (Tac) | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Randomization | 51.08 g/m^2.7 | Standard Deviation 14.11 |
| Standard CNI (Tac) | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Month 24 | 45.63 g/m^2.7 | Standard Deviation 13.5 |
| Standard CNI (CsA) | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Randomization | 51.13 g/m^2.7 | Standard Deviation 12.7 |
| Standard CNI (CsA) | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Month 24 | 47.91 g/m^2.7 | Standard Deviation 12.71 |
| Standard CNI (CsA) | Change in Left Ventricular Mass Index (LVMi) From Randomization to Month 12 and Month 24 | Month 12 | 50.96 g/m^2.7 | Standard Deviation 13 |
Secondary
Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis)
(treated BPAR ≥ IB, graft loss or death)A comparison of the incidence rates for the individual components of the composite efficacy endpoint between treatment arms
Time frame: at 24 months post-transplantation
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite tBPAR>=IB, graft loss, death, loss f/u | 35 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IB | 14 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Subclinical Acute rejection | 0 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite failure: tBPAR>=IB, graft loss, death | 27 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IA | 16 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Acute rejection (AR) | 52 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR>=IB | 18 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | treated biopsy proven acute rejection (tBPAR) | 32 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Treated Acute rejection (tAR) | 40 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Antibody mediated rejection (AMR) | 16 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | biopsy proven acute rejection (BPAR) | 37 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=III | 0 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Graft loss | 4 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Antibody tBPAR | 2 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IIB | 2 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Death | 8 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite of graft loss or Death | 10 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IIA | 3 Number of incidence |
| Everolimus | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Suspected Acute rejection | 61 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=III | 0 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite failure: tBPAR>=IB, graft loss, death | 8 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite tBPAR>=IB, graft loss, death, loss f/u | 14 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite of graft loss or Death | 6 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR>=IB | 3 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Graft loss | 2 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Death | 5 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Suspected Acute rejection | 27 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Subclinical Acute rejection | 0 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Acute rejection (AR) | 14 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Treated Acute rejection (tAR) | 9 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | biopsy proven acute rejection (BPAR) | 8 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | treated biopsy proven acute rejection (tBPAR) | 7 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IA | 3 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IB | 3 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IIA | 0 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IIB | 0 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Antibody tBPAR | 1 Number of incidence |
| Standard CNI (Tac) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Antibody mediated rejection (AMR) | 4 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IA | 8 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Suspected Acute rejection | 19 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Antibody mediated rejection (AMR) | 3 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IB | 5 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Death | 4 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Antibody tBPAR | 1 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IIA | 1 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Graft loss | 2 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite failure: tBPAR>=IB, graft loss, death | 8 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=IIB | 0 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR>=IB | 5 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Treated Acute rejection (tAR) | 14 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite of graft loss or Death | 4 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | biopsy proven acute rejection (BPAR) | 13 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Acute rejection (AR) | 15 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | tBPAR=III | 0 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | treated biopsy proven acute rejection (tBPAR) | 13 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Subclinical Acute rejection | 0 Number of incidence |
| Standard CNI (CsA) | Comparison of Incidence Rates of Efficacy Endpoints Between Treatment Arms (Full Analysis Set - 24 Month Analysis) | Composite tBPAR>=IB, graft loss, death, loss f/u | 15 Number of incidence |
Secondary
Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24
Efficacy failure rate used the composite endpoint of: (1) treated biopsy-proven acute rejection (BPAR)\*, (2) graft loss\*\*, or (3) death . \*A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. \*\*Graft loss is defined as when the allograft was presumed lost on the day the participant started dialysis and was not able to subsequently be removed from dialysis or re-transplanted.
Time frame: at 12 months and month 24 post-transplantation
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Everolimus | Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 | Month 12 | 21 Number of incidence |
| Everolimus | Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 | Month 24 | 27 Number of incidence |
| Standard CNI (Tac) | Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 | Month 12 | 4 Number of incidence |
| Standard CNI (Tac) | Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 | Month 24 | 8 Number of incidence |
| Standard CNI (CsA) | Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 | Month 12 | 8 Number of incidence |
| Standard CNI (CsA) | Incidence of Composite Efficacy Endpoint for Each Arm at Month 12 and Month 24 | Month 24 | 8 Number of incidence |