Gastrointestinal Tolerability of MMF vs EC-MPS in Maintenance Transplant Patients Treated With Calcineurin Inhibitors

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to assess the gastrointestinal tolerability of EC-MPS compared to MMF in maintenance transplant patients on a calcineurin inhibitor regimen, who require MMF dose reductions of 25% or more due to GI complications. The tested hypothesis is that the EC-MPS treatment is superior to the MMF therapy in terms of tolerability and that patients on the EC-MPS formulation will be able to tolerate higher doses compared to those on MMF.

Detailed Description
-----------------
The use of mycophenolate mofetil (MMF) in combination with a calcineurin inhibitor (CNI: tacrolimus or cyclosporine) has been shown to improve graft survival in renal, cardiac and liver transplantation patients. However, its use has been associated with significant side effects, including gastrointestinal complications, causing dose reductions, interruption or termination of the therapy. An alternate formulation: enteric coated mycophenolate sodium (EC-MPS) was designed to alleviate the severity of upper gastrointestinal side effects. Several trials detailed in the protocol suggest a benefit in GI related health following conversion from MMF to EC-MPS, however we believe that robust data are lacking.

Official Title
-----------------
A Single Centre, Prospective, Open-Label, Parallel Group, Randomized Study to Compare the Gastrointestinal Tolerability of Mycophenolate Mofetil (MMF, CellCept) and Enteric-Coated Mycophenolate Sodium (EC-MPS, Myfortic) in Maintenance Transplant Patients Treated With Calcineurin Inhibitors

Conditions
-----------------
Organ Transplantation

Intervention / Treatment
-----------------
* Drug: MMF
* Drug: EC-MPS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: recipients of liver or kidney or heart or lung or kidney/pancreas transplants at least 1 month post solid organ transplant on an immunosuppressive regimen which includes MMF in combination with cyclosporine A or tacrolimus previous MMF dose reduction of minimum of 25% of total dose due to at least one gastrointestinal complication with MMF therapy age of 18-75 years Exclusion Criteria: less than 1 month post transplant allergy (hypersensitivity) to MPA, MMF, EC-MPS or to any ingredients of Myfortic or CellCept unwillingness or inability to give written consent pregnant or nursing women, or women planning to become pregnant patients with GI symptoms due to reasons other than related to MMF therapy active Post Transplant Lymphoproliferative Disease (PTLD) significant or uncontrolled concomitant infections or other serious medical problems active bacterial, viral or fungal infection inability to self-administer the Quality of Life questionnaires

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>MMF | Drug: MMF<br>* Gradual optimization of drug dosage, as clinically tolerated.<br>* Other names: CellCept;|
| Active Comparator: B<br>EC-MPS | Drug: EC-MPS<br>* Conversion from MMF to EC-MPS. Gradual optimization of drug dosage, as clinically tolerated.<br>* Other names: Myfortic;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of patients with at least 1 GI symptom that is continuing or starting after the 1-month dose stabilization period |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis and comparison of various Gastrointestinal Symptom Rating and Quality of Life Questionnaire (the GSRS, GIQLI, PGWB,OTE for HRQoL) scores across and within the 2 cohorts. |  | At months 1, 3, 6, 12 post-study start | 
| Incidence and severity of adverse events |  | months 3, 6, 12 | 
| Patient survival, graft survival and rejection episodes across the 2 cohorts |  | months 3, 6, 12 | 
| Dose reductions, interruptions, fractionations and patient withdrawals across the two cohorts due to adverse events |  | Months 6, 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug tolerance, Quality of Life