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

The Washington University

Status and phase: Terminated; Phase 4

Conditions: Gastrointestinal Disorder, Functional; Kidney Transplant Rejection

Treatments: Drug: Mycophenolic Acid; Drug: Everolimus

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02974686

201603167

CRAD001AUS209T (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Kidney transplant recipients at Washington University/Barnes-Jewish Hospital
2. Experiencing GI toxicity from MPA as determined by the treating physician within 12 months post-renal transplant
3. On standard immunosuppression with tacrolimus and prednisone

Exclusion criteria

1. Dual organ or kidney after another solid organ transplant

2. Presence of a preexisting significant GI condition that does not have a presumed causal relationship with MPA

3. Evidence of any GI disorder induced by an infection, underlying medical condition, or concomitant medication other than MPA

4. Estimated glomerular filtration rate (eGFR) <40 ml/min at time of possible conversion

5. Proteinuria >1 gram/day at time of possible conversion

6. 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

7. Wound healing issues at time of possible conversion (eg, wound dehiscence, wound infection, incisional hernia, lymphocele, seroma)

8. Elevated total cholesterol (>350 mg/dL) and/or triglycerides (>500 ng/dL) at time of possible conversion

9. Hypersensitivity to everolimus, sirolimus, or other rapamycin derivatives

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1 participants in 2 patient groups

Interventional (EVR)

Active Comparator group

Description:

Patients experiencing gastrointestinal adverse effects in the first year post transplant will be converted from mycophenolate to everolimus

Treatment:

Drug: Everolimus

Prior Agent (MPA)

Active Comparator group

Description:

Patient will have baseline data collected while on MPA for comparison with EVR

Treatment:

Drug: Mycophenolic Acid