Trial Outcomes & Findings for Tacrolimus/Everolimus Versus Tacrolimus/Enteric-Coated Mycophenolate Sodium (NCT NCT01680861)

NCT ID: NCT01680861

Last Updated: 2016-12-15

Results Overview

BPAR (biopsy-proven acute rejection) incidence during the first 12 months post-transplant. Grading is determined using standard Banff criteria.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 32 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2016-12-15

Participant Flow

Participant milestones

Measure	Tacrolimus/Everolimus our experimental maintenance arm: Target 12-hr Tacrolimus trough level: 5-8 ng/mL Target 12-hr Everolimus trough level: 3-8 ng/mL.	Tacrolimus/EC-MPS our standard maintenance arm: Target 12-hr Tacrolimus trough level: 5-8 ng/mL Target EC-MPS dose: 720 mg PO BID (as tolerated).
Early Post-transplant Period STARTED	16	16
Early Post-transplant Period COMPLETED	15	15
Early Post-transplant Period NOT COMPLETED	1	1
First 12 Months Post-transplant STARTED	15	15
First 12 Months Post-transplant COMPLETED	15	15
First 12 Months Post-transplant NOT COMPLETED	0	0

Reasons for withdrawal

Measure	Tacrolimus/Everolimus our experimental maintenance arm: Target 12-hr Tacrolimus trough level: 5-8 ng/mL Target 12-hr Everolimus trough level: 3-8 ng/mL.	Tacrolimus/EC-MPS our standard maintenance arm: Target 12-hr Tacrolimus trough level: 5-8 ng/mL Target EC-MPS dose: 720 mg PO BID (as tolerated).
Early Post-transplant Period Protocol Violation	1	1

Baseline Characteristics

Tacrolimus/Everolimus Versus Tacrolimus/Enteric-Coated Mycophenolate Sodium

Baseline characteristics by cohort

Measure	Tacrolimus/Everolimus n=15 Participants our experimental maintenance arm.	Tacrolimus/EC-MPS n=15 Participants our standard maintenance arm.	Total n=30 Participants Total of all reporting groups
Age, Continuous	49.9 years STANDARD_DEVIATION 10.5 • n=5 Participants	48.5 years STANDARD_DEVIATION 11.2 • n=7 Participants	49.2 years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized African-American	5 participants n=5 Participants	2 participants n=7 Participants	7 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	7 participants n=5 Participants	10 participants n=7 Participants	17 participants n=5 Participants
Race/Ethnicity, Customized White/Asian	3 participants n=5 Participants	3 participants n=7 Participants	6 participants n=5 Participants
Region of Enrollment United States	15 participants n=5 Participants	15 participants n=7 Participants	30 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

BPAR (biopsy-proven acute rejection) incidence during the first 12 months post-transplant. Grading is determined using standard Banff criteria.

Outcome measures

Measure	Tacrolimus/Everolimus n=15 Participants our experimental maintenance arm.	Tacrolimus/EC-MPS n=15 Participants our standard maintenance arm.
BPAR (Biopsy-proven Acute Rejection) Incidence During the First 12 Months Post-transplant	1 participants	3 participants

SECONDARY outcome

Timeframe: 1 year

Incidence of (biopsy-proven) chronic allograft nephropathy (CAI) [interstitial fibrosis and tubular atrophy, using standard Banff criteria] at 12 months post-transplant.

Outcome measures

Measure	Tacrolimus/Everolimus n=15 Participants our experimental maintenance arm.	Tacrolimus/EC-MPS n=15 Participants our standard maintenance arm.
Incidence of Chronic Allograft Nephropathy (CAI) at 12 Months Post-transplant	3 participants	3 participants

SECONDARY outcome

Timeframe: during the first 12 months post-transplant

Outcome measures

Measure	Tacrolimus/Everolimus n=15 Participants our experimental maintenance arm.	Tacrolimus/EC-MPS n=15 Participants our standard maintenance arm.
Graft Loss (Return to Permanent Dialysis or Death)	0 participants	0 participants

SECONDARY outcome

Timeframe: at 1 month post-transplant

using the abbreviated MDRD formula.

Outcome measures

Measure	Tacrolimus/Everolimus n=15 Participants our experimental maintenance arm.	Tacrolimus/EC-MPS n=15 Participants our standard maintenance arm.
eGFR (Calculated Glomerular Filtration Rate), i.e., Renal Function, at 1 Month Post-transplant.	82.1 ml/min per 1.73 m2 Standard Error 8.2	62.1 ml/min per 1.73 m2 Standard Error 6.2

SECONDARY outcome

Timeframe: at 3 months post-transplant

Renal function as determined by the estimated glomerular filtration rate (eGFR) at 3 months post-transplant, using the abbreviated MDRD formula.

Outcome measures

Measure	Tacrolimus/Everolimus n=15 Participants our experimental maintenance arm.	Tacrolimus/EC-MPS n=15 Participants our standard maintenance arm.
eGFR (Renal Function) at Month 3 Post-transplant	75.7 ml/min per 1.73 m^2 Standard Error 6.0	65.6 ml/min per 1.73 m^2 Standard Error 4.2

SECONDARY outcome

Timeframe: at 6 months post-transplant

using the abbreviated MDRD formula.

Outcome measures

Measure	Tacrolimus/Everolimus n=13 Participants our experimental maintenance arm.	Tacrolimus/EC-MPS n=14 Participants our standard maintenance arm.
eGFR (Renal Function) at 6 Months Post-transplant	66.7 ml/min per 1.73 m2 Standard Error 5.0	63.7 ml/min per 1.73 m2 Standard Error 3.9

SECONDARY outcome

Timeframe: during the first 12 months post-transplant

Population: Note: one patient in the Tacrolimus/EC-MPS arm discontinued EC-MPS at 12 months post-transplant following a colon cancer diagnosis and the necessity to receive chemotherapy.

Outcome measures

Measure	Tacrolimus/Everolimus n=15 Participants our experimental maintenance arm.	Tacrolimus/EC-MPS n=15 Participants our standard maintenance arm.
Discontinuance of Any Study Medication (Tacrolimus, Everolimus, or EC-MPS)	0 participants	1 participants

Adverse Events

Tacrolimus/Everolimus

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Tacrolimus/EC-MPS

Serious events: 4 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tacrolimus/Everolimus n=15 participants at risk our experimental maintenance arm	Tacrolimus/EC-MPS n=15 participants at risk our standard maintenance arm
Infections and infestations Urinary Tract Infection Requiring Hospitalization	6.7% 1/15 • Number of events 1 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.	0.00% 0/15 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.
Infections and infestations Ear Infection Requiring Hospitalization	0.00% 0/15 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.	6.7% 1/15 • Number of events 1 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.
Infections and infestations Pneumonia	0.00% 0/15 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.	6.7% 1/15 • Number of events 1 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.
Infections and infestations Sepsis	6.7% 1/15 • Number of events 1 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.	0.00% 0/15 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.
Infections and infestations CMV Viremia	0.00% 0/15 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.	6.7% 1/15 • Number of events 1 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.
Infections and infestations Polyoma Viral Infection (Viremia)	13.3% 2/15 • Number of events 2 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.	6.7% 1/15 • Number of events 1 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.
Infections and infestations Herpes Zoster Infection	6.7% 1/15 • Number of events 1 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.	0.00% 0/15 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.
Endocrine disorders NODAT	13.3% 2/15 • Number of events 2 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.	0.00% 0/15 • during the first 12 months post-transplant, Here, we are reporting the numbers of patients who 1) developed an infection requiring hospitalization (or had an opportunistic viral infection not requiring hospitalization) and 2) developed NODAT (new onset diabetes after transplant) (among patients not having pretransplant diabetes mellitus) during the first 12 months post-transplant. Please note that adverse events specified to be studied as secondary outcomes were the only AEs collected in our randomized trial.

Other adverse events

Adverse event data not reported

Additional Information

Jeffrey Gaynor, Ph.D. biostatistician

Miami Transplant Institute

Email: jgaynor@med.miami.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place