Conversion From MPA to Zortress (Everolimus) for GI Toxicity Post-renal Transplantation

Study Overview
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Brief Summary
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Patients who receive renal transplantation at Barnes Jewish Hospital (BJH) are placed on triple maintenance immunosuppression, which means that patients take 3 types of immunosuppression drugs to suppress their immune system including tacrolimus, mycophenolate (MPA), and prednisone. However, due to the effects of MPA on the gastrointestinal tract, patients often complain of GI adverse effects. Current practice is to either dose-reduce MPA or convert the patient to an alternative agent, typically Azathioprine. Both of these strategies have limitations, largely due to concerns related to efficacy. Everolimus (EVR) has demonstrated similar efficacy to MPA in renal transplantation and may offer a benefit related to GI adverse effects, so the investigators will convert patients to EVR in this study. Patients who are within their first year post-transplant will be converted to EVR upon enrollment in the study, and serial measurements ,or a series of measurements looking for an increase or decrease over time, of GI adverse effects will be conducted over 1 year post-enrollment.

Official Title
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Conversion From MPA to Zortress (Everolimus) for GI Toxicity Post-renal Transplantation

Conditions
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Kidney Transplant Rejection, Gastrointestinal Disorder, Functional

Intervention / Treatment
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* Drug: Everolimus
* Drug: Mycophenolic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Kidney transplant recipients at Washington University/Barnes-Jewish Hospital Experiencing GI toxicity from MPA as determined by the treating physician within 12 months post-renal transplant On standard immunosuppression with tacrolimus and prednisone Exclusion Criteria: Dual organ or kidney after another solid organ transplant Presence of a preexisting significant GI condition that does not have a presumed causal relationship with MPA Evidence of any GI disorder induced by an infection, underlying medical condition, or concomitant medication other than MPA Estimated glomerular filtration rate (eGFR) <40 ml/min at time of possible conversion Proteinuria >1 gram/day at time of possible conversion Profound bone marrow suppression at the time of possible conversion as defined as: Hemoglobin <10 g/dL White blood cell (WBC) < 3 K/cumm Platelets <100 K/cumm Wound healing issues at time of possible conversion (eg, wound dehiscence, wound infection, incisional hernia, lymphocele, seroma) Elevated total cholesterol (>350 mg/dL) and/or triglycerides (>500 ng/dL) at time of possible conversion Hypersensitivity to everolimus, sirolimus, or other rapamycin derivatives

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Interventional (EVR)<br>Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus | Drug: Everolimus<br> <br> * Other names: Zortress;|
| Active Comparator: Prior Agent (MPA)<br>Patient will have baseline data collected while on MPA for comparison with EVR | Drug: Mycophenolic Acid<br> <br> * Other names: Myfortic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal Symptom Rating Scale | Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal Symptom Rating Scale | Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality. | 1, 6, and 12 months | 
| Biopsy Proven Acute Rejection | Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality. | 12 months |