Trial Outcomes & Findings for Novartis Everolimus Transition (NCT NCT02096107)

NCT ID: NCT02096107

Last Updated: 2018-08-08

Results Overview

Measure and compare the change in interstitial fibrosis (morphometric analysis of trichrome stained slides) at one-year post-transplant in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen. The scale is a percentage of the tissue that demonstrates fibrosis. The scale range is 0 to 100%. The higher the percentage, the worse the fibrosis and the poorer the prognosis. A lower score (percentage) is therefore better.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

1 year

Results posted on

2018-08-08

Participant Flow

Participant milestones

Participant milestones
Measure	Low Intensity Tacrolimus Low tacrolimus, everolimus, and steroids Convert mycophenolate to everolimus (concentration goal of 3-8 ng/mL) with subsequent reduction in exposure to tacrolimus (concentration of 2-5 ng/mL)	Standard of Care Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus (concentration goal of 5-12 ng/mL), mycophenolate mofetil and steroids
Overall Study STARTED	30	30
Overall Study COMPLETED	30	30
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Novartis Everolimus Transition

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Low Intensity Tacrolimus n=30 Participants Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=30 Participants Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids	Total n=60 Participants Total of all reporting groups
Age, Continuous	51.0 years STANDARD_DEVIATION 13.6 • n=5 Participants	51.6 years STANDARD_DEVIATION 12.1 • n=7 Participants	51.3 years STANDARD_DEVIATION 12.85 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	11 Participants n=7 Participants	14 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants	19 Participants n=7 Participants	46 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants	19 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) White	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Weight	89.1 kg STANDARD_DEVIATION 17 • n=5 Participants	84.7 kg STANDARD_DEVIATION 16.6 • n=7 Participants	86.9 kg STANDARD_DEVIATION 16.8 • n=5 Participants
BMI	28.6 kg/m^2 STANDARD_DEVIATION 4.8 • n=5 Participants	28.7 kg/m^2 STANDARD_DEVIATION 4.5 • n=7 Participants	28.7 kg/m^2 STANDARD_DEVIATION 4.6 • n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: The number of subjects analyzed for the fibrosis assessment was 15 in each group, because biopsy samples for both baseline and end of follow-up were only able to be obtained from 15 subjects per group.

Outcome measures

Outcome measures
Measure	Low Intensity Tacrolimus n=15 Participants Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=15 Participants Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids
Kidney Allograft Fibrosis Assessment Baseline	22.9 % of fibrosis Interval 17.9 to 25.7	20.8 % of fibrosis Interval 18.4 to 30.4
Kidney Allograft Fibrosis Assessment End of Follow-up	22.9 % of fibrosis Interval 18.6 to 28.1	27.8 % of fibrosis Interval 18.7 to 31.0

SECONDARY outcome

Timeframe: 1 year

Measure and compare the estimated GFR (using the 4-variable modified MDRD equation) in patients converted to everolimus, low intensity tacrolimus and prednisone versus the standard of care tacrolimus, mycophenolate and prednisone regimen, both at one year and two years post-transplant.

Outcome measures

Outcome measures
Measure	Low Intensity Tacrolimus n=30 Participants Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=30 Participants Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids
Renal Function Measured by Estimated Glomerular Filtration Rate (eGFR)	59 mL/min/1.73 m^2 Standard Deviation 14	56 mL/min/1.73 m^2 Standard Deviation 15

SECONDARY outcome

Timeframe: 1 year

Compare the patient and graft survival rates at one-year post-transplant in each group.

Outcome measures

Outcome measures
Measure	Low Intensity Tacrolimus n=30 Participants Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=30 Participants Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids
Kidney Allograft Survival	100 percentage of patients graft survival	100 percentage of patients graft survival

SECONDARY outcome

Timeframe: 2 year

Measure and compare the rates of immunosuppressant discontinuation and modification for each group.

Outcome measures

Outcome measures
Measure	Low Intensity Tacrolimus n=30 Participants Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=30 Participants Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids
Percentage of Participants Discontinuing or Modifying Immunosuppressant Use	37 percentage of participants	20 percentage of participants

SECONDARY outcome

Timeframe: 2 year

Measure and compare the incidence of significant immunosuppressant-related adverse drug reactions for each group.

Outcome measures

Outcome measures
Measure	Low Intensity Tacrolimus n=30 Participants Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=30 Participants Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids
Adverse Drug Reactions	11 Participants	6 Participants

SECONDARY outcome

Timeframe: 2 year

Compare the rates of post-transplant infections, including CMV, BK, and admissions to the hospital for infectious causes in each group.

Outcome measures

Outcome measures
Measure	Low Intensity Tacrolimus n=30 Participants Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=30 Participants Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids
Infection	17 percentage of subjects with infection	30 percentage of subjects with infection

Adverse Events

Low Intensity Tacrolimus

Serious events: 8 serious events

Other events: 11 other events

Deaths: 0 deaths

Standard of Care

Serious events: 6 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Low Intensity Tacrolimus n=30 participants at risk Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=30 participants at risk Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids
Renal and urinary disorders Hospitalization	26.7% 8/30 • Number of events 8 • 2 years	20.0% 6/30 • Number of events 6 • 2 years
Renal and urinary disorders Infections	13.3% 4/30 • Number of events 4 • 2 years	10.0% 3/30 • Number of events 3 • 2 years

Other adverse events

Other adverse events
Measure	Low Intensity Tacrolimus n=30 participants at risk Low tacrolimus, everolimus, and steroids Everolimus: Convert mycophenolate to everolimus with subsequent reduction in exposure to tacrolimus	Standard of Care n=30 participants at risk Tacrolimus, mycophenolate mofetil and steroids Standard of Care: Tacrolimus, mycophenolate mofetil and steroids
Renal and urinary disorders Immunosuppression held or modified	36.7% 11/30 • Number of events 11 • 2 years	20.0% 6/30 • Number of events 6 • 2 years

Additional Information

David Taber

Medical University of South Carolina

Phone: 843-792-3368

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place