This is a pilot study to determine if extended release Envarsus at an optimal level is just as effective as more invasive standard therapies for subclinical (mild) AMR (antibody mediated rejection) in kidney transplant patients. Subjects will be randomized to either conversion to Envarsus XR (extended release); or, to a standard of care regimen of plasma exchange/IVIG (intravenous immunoglobulin)/rituximab treatments.
There is currently minimal data to guide treatment of mild graft damage in kidney transplant patients. Some of the current therapies used often come with dangerous complications (infections, malignancies, etc.). This is a pilot study to determine if extended release Envarsus at an optimal level is just as effective as more invasive standard therapies for subclinical (mild) AMR (antibody mediated rejection) in kidney transplant patients. The subjects will be randomized to either conversion from their current tacrolimus regimen to Envarsus XR (a once a day, extended release version of tacrolimus); or, to a regimen of 5 plasma exchanges/IVIG (intravenous immunoglobulin) treatments and one treatment with rituximab. Subjects who are within their first year of transplant will visit their doctor monthly for regular tests and checks and then will have a kidney biopsy at 6 months. Subjects who had their transplant over a year prior will see the doctor for tests and checks at 1, 3 and 5 months and then will have a biopsy of the kidney at month 6.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
4
Switching from current version of tacrolimus to the extended release, once a day version (Envarsus) and titrating dose to achieve an optimal trough level. Goal trough tac level \> 8 ng/ml, MPA at 720 mg bid unless medically contraindicated, prednisone at current dose (5mg) or continue taper to 5mg per center standard of care protocol.
Plasma exchange x 5 treatments, each followed by IVIG 200 mg/kg except last dose of 1 gm/kg. Rituximab 375 mg/m2 following final plasma exchange treatment.
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
Change in Acute Inflammatory Histologic Parameters
Any increase or reduction in ptc+g+C4d score by Banff 2013 criteria) from baseline (pre-treatment) to 6 month (post-treatment initiation). Analysis will comprise exact chi-squared tests for comparison of binomial proportions of histological response between the two treatment groups.
Time frame: Baseline and 6 months
Change in MDRD GFR (Modification of Diet in Renal Disease Glomerular Filtration Rate)
Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.
Time frame: 6 and 12 months
Change in Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI) Level
Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.
Time frame: 6 and 12 months
Change in serum creatinine
Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests.
Time frame: 6 and 12 months
Graft Survival
Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests.
Time frame: 6 and 12 months
Patient Survival
Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests.
Time frame: 6 and 12 months
Evaluation of Adverse Events
All potential adverse events will be captured and recorded by study coordinators during post-treatment standard of care clinic visits, and reviewed by PI. Adverse events will be reported for each group separately and compared using exact chi-squared tests.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 6 and 12 months