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

NCT02974686 | Terminated Phase 4 Results DMC

• 2 other identifiers: 201603167CRAD001AUS209T
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Kidney Transplant Rejection; Gastrointestinal Disorder, Functional

Outcome Measures

Primary Outcomes (1)

• Gastrointestinal Symptom Rating Scale

  Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.

  3 months

Secondary Outcomes (2)

• Gastrointestinal Symptom Rating Scale

  1, 6, and 12 months

• Biopsy Proven Acute Rejection

  12 months

Study Arms (2)

Interventional (EVR)

ACTIVE COMPARATOR

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

Drug: Everolimus

Prior Agent (MPA)

ACTIVE COMPARATOR

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

Drug: Mycophenolic Acid

Interventions

Everolimus DRUG

Also known as: Zortress

Interventional (EVR)

Mycophenolic Acid DRUG

Also known as: Cellcept, Myfortic

Prior Agent (MPA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Gastrointestinal Diseases

Interventions

Everolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Limitations and Caveats

Trial was terminated with only 1 participant enrolled. No data is reported here to maintain patient confidentiality.

Results Point of Contact

• Title: Dr. R. Delos Santos
• Organization: Washington University

delossantos@wustl.edu

314-362-8351

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2016
• First Posted: November 28, 2016
• Study Start: November 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: August 10, 2020
• Results First Posted: August 10, 2020

Record last verified: 2020-08

Locations

US (1)