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

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Transplant Rejection; Gastrointestinal Disorder, Functional
• Intervention / Treatment: Drug: Everolimus; Drug: Mycophenolic Acid

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: November 3, 2016
• First Submitted That Met QC Criteria: November 22, 2016
• First Posted (Estimate): November 28, 2016

Study Record Updates

• Last Update Posted (Actual): August 10, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Gastrointestinal Diseases; Digestive System Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid; Everolimus
• Other Study ID Numbers: 201603167; CRAD001AUS209T (Other Grant/Funding Number: Novartis Pharmaceuticals Company)