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Slower than expected recruitment rate
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| Name | Class |
|---|---|
| Veloxis Pharmaceuticals | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 - conversion to Envarsus XR | Active Comparator | Optimize: conversion to Envarsus XR (Tacrolimus Extended Release Oral Tablet [Envarsus]) with 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 |
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| Arm 2 - plasma exchange and IVIG | Active Comparator | Treat clinical AMR: 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tacrolimus Extended Release Oral Tablet [Envarsus] | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline and 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 and 12 months |
| Change in Donor-Specific Antibody (DSA) Mean Fluorescence Intensity (MFI) Level |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| James Cooper, M.D. | University of Colorado, Denver | Principal Investigator |
| Scott Davis, M.D. | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Colorado Anschutz Medical Campus | Aurora | Colorado | 80045 | United States |
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Only patients meeting histologic criteria for AMR by Banff 2013 criteria will be randomized (ptc + g + c4d ≥ 2). Subjects will be randomized to either undergo optimization (conversion to Envarsus with goal trough tacrolimus level > 8 ng/ml, mycophenolic acid at 720 mg, prednisone at current dose (5mg) or continue taper to 5mg per center standard of care protocol of or treatment.); or, to treat clinical AMR (antibody mediated rejection) with plasma exchange x 5 treatments, each followed by IVIG (intravenous immunoglobulin) 200 mg/kg except last dose of 1 gm/kg. Rituximab 375 mg/m2 following final plasma exchange treatment.
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| Plasma Exchange and IVIG (Intravenous Immunoglobulin ) | Other | 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. |
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Comparison of these levels and any changes of levels/rates using two-sided two-sample t-tests. |
| 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. | 6 and 12 months |
| Graft Survival | Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests. | 6 and 12 months |
| Patient Survival | Total and death-censored calculated using Kaplan-Meier methods and compared using logrank tests. | 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. | 6 and 12 months |
| ID | Term |
|---|---|
| D016559 | Tacrolimus |
| D010951 | Plasma Exchange |
| D016756 | Immunoglobulins, Intravenous |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D001803 | Blood Transfusion |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D010956 | Plasmapheresis |
| D001781 | Blood Component Removal |
| D016060 | Sorption Detoxification |
| D005112 | Extracorporeal Circulation |
| D013514 | Surgical Procedures, Operative |
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
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