Trial Outcomes & Findings for Concentration Controlled Everolimus With Reduced Dose Cyclosporine Versus Mycophenolate Mofetil With Standard Dose Cyclosporine in de Novo Renal Transplant Adult Recipients Treated With Basiliximab and Corticosteroids (NCT NCT00658320)

Last Updated: 2013-06-21

Results Overview

The composite efficacy endpoint consisted of treated biopsy proven acute rejection (BPAR) episodes, graft loss, death or loss to follow-up. A treated BPAR was defined as a biopsy graded IA, IB, IIA, IIB, or III and which was treated with anti-rejection therapy. The allograft was presumed to be lost on the day the patient starts dialysis and was not able to stop dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss. For the individual components (including loss of follow-up)of the composite endpoint, patients are counted for the first event to occur.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

122 participants

Primary outcome timeframe

12 months

Results posted on

2013-06-21

Participant Flow

Core Study randomization was conducted within 24 hours post reperfusion. Participants who completed the 12 month visit of the Core Study and met inclusion/exclusion criteria were eligible to participate in the Extension Study and continued the same treatment as the Core Study until Month 24.

Participant milestones

Participant milestones
Measure	Everolimus + Reduced Dose of Cyclosporine An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8 ng/mL). Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study. Everolimus was available after 24 months for compassionate use.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study.
Core Study: 12 Months STARTED	61	61
Core Study: 12 Months COMPLETED	56	58
Core Study: 12 Months NOT COMPLETED	5	3
Extension Study: Month 12 to Month 24 STARTED	53	57
Extension Study: Month 12 to Month 24 Extension ITT: Received Study Drug	50	50
Extension Study: Month 12 to Month 24 COMPLETED	47	50
Extension Study: Month 12 to Month 24 NOT COMPLETED	6	7
Extension Study: After Month 24 STARTED	44	0
Extension Study: After Month 24 COMPLETED	42	0
Extension Study: After Month 24 NOT COMPLETED	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Everolimus + Reduced Dose of Cyclosporine An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8 ng/mL). Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study. Everolimus was available after 24 months for compassionate use.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study.
Core Study: 12 Months Subject withdrew consent	5	3
Extension Study: Month 12 to Month 24 Subject withdrew consent	3	0
Extension Study: Month 12 to Month 24 Did not receive study drug in Extension	3	7
Extension Study: After Month 24 Subject withdrew consent	2	0

Baseline Characteristics

Concentration Controlled Everolimus With Reduced Dose Cyclosporine Versus Mycophenolate Mofetil With Standard Dose Cyclosporine in de Novo Renal Transplant Adult Recipients Treated With Basiliximab and Corticosteroids

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Everolimus + Reduced Dose of Cyclosporine n=61 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=61 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Total n=122 Participants Total of all reporting groups
Age Continuous	42.5 years STANDARD_DEVIATION 14.13 • n=5 Participants	38.6 years STANDARD_DEVIATION 11.36 • n=7 Participants	40.5 years STANDARD_DEVIATION 12.92 • n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	24 Participants n=7 Participants	39 Participants n=5 Participants
Sex: Female, Male Male	46 Participants n=5 Participants	37 Participants n=7 Participants	83 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Population: The Intent-To-Treat (ITT) population consisted of all patients randomized after transplantation.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=61 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=61 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Core Study: Number of Patients With Composite Efficacy Endpoint Composite Efficacy Endpoint	7 Participants	7 Participants
Core Study: Number of Patients With Composite Efficacy Endpoint Treated BPAR	3 Participants	5 Participants
Core Study: Number of Patients With Composite Efficacy Endpoint Graft Loss	0 Participants	0 Participants
Core Study: Number of Patients With Composite Efficacy Endpoint Death	0 Participants	0 Participants
Core Study: Number of Patients With Composite Efficacy Endpoint Loss to follow up (see caveats)	4 Participants	2 Participants

PRIMARY outcome

Timeframe: Month 24

Population: Participants from the Extension Intent-to-treat population with data available for analyses.

Renal function was assessed by glomerular filtration rate (GFR) using the MDRD formula: GFR \[mL/min/1.73m2\] = 186.3\*(C-1.154)\*(A-0.203)\*G\*R C is the serum concentration of creatinine \[mg/dL\] A is age \[years\] G = 0.742 when gender is female, otherwise G=1 R = 1.21 when race is black, otherwise R=1 Loss to follow up (in In Primary Core Outcome Measure) is composite efficacy failure and contains incidence of treated BPAR, graft loss, death or loss to follow-up

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=49 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=50 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula	58.90 mL/min/1.73m^2 Interval 14.4 to 118.9	54.95 mL/min/1.73m^2 Interval 28.3 to 92.7

PRIMARY outcome

Timeframe: Month 48

Population: Participants from the Extension Intent-to-treat population with data available for analyses.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=9 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using the Modification of Diet in Renal Disease (MDRD) Formula	59.80 mL/min/1.73m^2 Interval 36.8 to 72.0	—

SECONDARY outcome

Timeframe: 12 months

Population: The Intent-To-Treat (ITT) population consisted of all patients randomized after transplantation.

The allograft was presumed to be lost on the day the patient starts dialysis and was not able to stop dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss. A loss to follow-up in graft loss, death or loss to follow-up is a patient who did not experience graft loss or death and whose last day of contact was prior to Day 316, i.e. prior to the Month 12 visit window.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=61 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=61 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Core Study: Number Participants With Combined Graft Loss, Death or Loss to Follow-up	5 Participants	3 Participants

SECONDARY outcome

Timeframe: Month 12

Modification of Diet in Renal Disease (MDRD) formula is: Calculated GFR \[mL/min/1.73m\^2\] = 186.3\*(C\^-1.154)\*(A\^-0.203)\*G\*R where * C is the serum concentration of creatinine \[mg/dL\], * A is patient age at sample collection date \[years\], * G=0.742 when gender is female, otherwise G=1, * R=1.21 when race is black, otherwise R=1

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=61 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=61 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Core Study: Renal Function Measured by Calculated Glomerular Filtration Rate (cGFR) Using Modification of Diet in Renal Disease (MDRD) Formula	58.00 mL/min/1.73m^2 Full Range 18.993 • Interval 17.8 to 123.3	55.25 mL/min/1.73m^2 Full Range 15.227 • Interval 26.1 to 111.8

SECONDARY outcome

Timeframe: 24 Months

Population: Extension Intent-to-treat population.

Graft loss was defined as the day the patient started dialysis and was not able to subsequently be removed from dialysis or re-transplant. Loss-to-follow was a patient who did not experience a treated BPAR, graft loss or death and whose last day of contact was prior to Month 24. A Graft Biopsy was done within 48 hours of suspect rejection. Biopsies were read by the local pathologist according to the updated Banff '97 criteria. Treated BPAR was based on local laboratory biopsy results and was defined as a biopsy Banff criteria graded IA to III that was treated with anti-rejection therapy.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=50 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=50 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) Combined Efficacy Endpoint	4 Participants	5 Participants
Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) Treated BPAR	3 Participants	5 Participants
Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) Graft Loss	0 Participants	0 Participants
Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) Death	0 Participants	0 Participants
Extension Study: Number of Participants With Combined Efficacy Endpoint: Graft Loss, Death, Loss to Follow-up and/or Treated Biopsy Proven Acute Rejection (BPAR) Loss to follow-up	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Month 24, Month 48

Population: Participants from the Extension Intent-to-treat population with data available for analyses.

The Nankivell formula was used to calculate GFR at Month 24: GFR\[mL/min\]=6.7/C + W/4 - UREA/2 - 100/H\^2 + 35 (25 for females) W= body weight \[kg\] H= height \[m\] C= serum creatinine \[mmol/L\] UREA= serum urea \[mmol\\L\]

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=46 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=50 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula Month 24	63.49 mL/min Standard Deviation 20.479	59.24 mL/min Standard Deviation 13.840
Extension Study: Renal Function Measured by Calculated Glomerular Filtration Rate (GFR) Using the Nankivell Formula Month 48 (9,0)	60.16 mL/min Standard Deviation 9.892	NA mL/min Standard Deviation NA 0 participants in the Mycophenolate mofetil (MMF) + Standard dose of cyclosporine arm after Week 24.

SECONDARY outcome

Timeframe: 24 Months

Population: Participants from the Extension Safety Population.

Additional information about Adverse Events can be found in the Adverse Event Section.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=50 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=50 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Extension Study: Number of Participants With Adverse Events and Serious Adverse Events Adverse Events	50 Participants	50 Participants
Extension Study: Number of Participants With Adverse Events and Serious Adverse Events Serious Adverse Events	30 Participants	30 Participants

SECONDARY outcome

Timeframe: Month 24, Month 48

Population: Participants from the Extension safety population with data available for analyses.

Blood was collected at all visits after Day 3 for trough (collected 5 minutes before study drug dose) everolimus levels and was analyzed at a central laboratory using liquid chromatography mass spectrometry.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=45 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Extension Study: Everolimus Trough Levels Month 24	5.258 ng/mL Standard Deviation 1.1170	—
Extension Study: Everolimus Trough Levels Month 48 (n=8)	4.408 ng/mL Standard Deviation 0.5986	—

SECONDARY outcome

Timeframe: Month 24, Month 48

Population: Participants from the Extension safety population with data available for analyses.

Blood was collected at all visits after Day 3 for trough (collected 5 minutes before study drug dose) cyclosporine levels and was analyzed at a central laboratory using immunoassay.

Outcome measures

Outcome measures
Measure	Everolimus + Reduced Dose of Cyclosporine n=44 Participants An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8ng/mL).Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=48 Participants Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice.
Extension Study: Cyclosporine Trough Levels Month 24	54.1 ng/mL Standard Deviation 39.07	105.5 ng/mL Standard Deviation 44.16
Extension Study: Cyclosporine Trough Levels Month 48 (n=7,0)	34.2 ng/mL Standard Deviation 37.94	NA ng/mL Standard Deviation NA 0 participants in the Mycophenolate mofetil (MMF) + Standard dose of cyclosporine arm at Week 48.

Adverse Events

Everolimus + Reduced Dose of Cyclosporine

Serious events: 37 serious events

Other events: 61 other events

Deaths: 0 deaths

Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine

Serious events: 37 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Everolimus + Reduced Dose of Cyclosporine n=61 participants at risk An initial everolimus dose of 0.75 mg orally twice daily (1.5 mg/day) was administered 24-36 hours from reperfusion after transplantation and dose adjustments based on everolimus trough level (target trough level 3-8 ng/mL). Reduced dose of cyclosporine was initiated either pre-transplantation or within 24 hours after transplantation following the local regimen. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study. Everolimus was available after 24 months for compassionate use.	Mycophenolate Mofetil (MMF) + Standard Dose of Cyclosporine n=61 participants at risk Patients were treated with 1 gram twice a day (2 grams/day) of Mycophenolate mofetil (MMF) and standard dose of cyclosporine for 12 months post renal transplant. Patients were treated with antibody induction therapy using 20 mg basiliximab two hours prior to transplant and 20 mg basiliximab 4 days post transplant or according to local practice. Corticosteroids were administered according to local practice. Patients were treated for 12 months in the core study and 12 months in the extension study.
Blood and lymphatic system disorders Pancytopenia	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Eye disorders Cataract	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Eye disorders Cataract nuclear	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Gastrointestinal disorders Diarrhoea	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Gastrointestinal disorders Enteritis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Gastrointestinal disorders Gastritis	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Gastrointestinal disorders Inguinal hernia	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Gastrointestinal disorders Vomiting	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
General disorders Impaired healing	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
General disorders Pyrexia	4.9% 3/61 Combined data of adverse events that occurred in the Core and Extension studies.	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Hepatobiliary disorders Cholelithiasis	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Hepatobiliary disorders Hepatic function abnormal	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Hepatobiliary disorders Hepatobiliary disease	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Adenoviral haemorrhagic cystitis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Adenovirus infection	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Cellulitis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Cystitis viral	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Cytomegalovirus infection	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	18.0% 11/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Cytomegalovirus viraemia	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Enterocolitis infectious	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Gastroenteritis	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.	6.6% 4/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Herpes zoster	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Mycobacterium avium complex infection	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Pertussis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Pharyngitis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Pneumocystis jiroveci pneumonia	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Pneumonia	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Pneumonia bacterial	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Pneumonia cytomegaloviral	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Renal cyst infection	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Rhinitis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Infections and infestations Urinary tract infection	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.
Injury, poisoning and procedural complications Incisional hernia	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Injury, poisoning and procedural complications Kidney rupture	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Injury, poisoning and procedural complications Lower limb fracture	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Injury, poisoning and procedural complications Ureteric anastomosis complication	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Investigations Bacterial test positive	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Investigations Blood beta-D-glucan increased	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Investigations Blood creatinine increased	8.2% 5/61 Combined data of adverse events that occurred in the Core and Extension studies.	9.8% 6/61 Combined data of adverse events that occurred in the Core and Extension studies.
Investigations Blood urea increased	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Investigations C-reactive protein increased	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Investigations Cytomegalovirus test positive	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.	16.4% 10/61 Combined data of adverse events that occurred in the Core and Extension studies.
Investigations HLA marker study positive	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Metabolism and nutrition disorders Dehydration	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Metabolism and nutrition disorders Diabetes mellitus	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Musculoskeletal and connective tissue disorders Osteonecrosis	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign ovarian tumour	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Diffuse large B-cell lymphoma	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Calculus urinary	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Focal segmental glomerulosclerosis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Glomerulonephritis membranous	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Hydronephrosis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders IgA nephropathy	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Nephropathy toxic	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Nephrotic syndrome	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Proteinuria	8.2% 5/61 Combined data of adverse events that occurred in the Core and Extension studies.	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Renal impairment	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Renal and urinary disorders Renal tubular necrosis	3.3% 2/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Reproductive system and breast disorders Azoospermia	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Reproductive system and breast disorders Prostatitis	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Respiratory, thoracic and mediastinal disorders Pneumomediastinum	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Respiratory, thoracic and mediastinal disorders Pneumothorax	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	6.6% 4/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Skin and subcutaneous tissue disorders Subcutaneous emphysema	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.
Vascular disorders Angiopathy	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.
Vascular disorders Deep vein thrombosis	1.6% 1/61 Combined data of adverse events that occurred in the Core and Extension studies.	0.00% 0/61 Combined data of adverse events that occurred in the Core and Extension studies.