Clinical trial NCT00611494: Gastrointestinal Tolerability of MMF vs EC-MPS in Maintenance Transplant Patients Treated With Calcineurin Inhibitors
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Organ Transplantation
Keywords: Drug tolerance
Quality of Life
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2008-02-11
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: The number of patients with at least 1 GI symptom that is continuing or starting after the 1-month dose stabilization period
timeFrame: 12 months
Secondary outcomes:
measure: 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.
timeFrame: At months 1, 3, 6, 12 post-study start
measure: Incidence and severity of adverse events
timeFrame: months 3, 6, 12
measure: Patient survival, graft survival and rejection episodes across the 2 cohorts
timeFrame: months 3, 6, 12
measure: Dose reductions, interruptions, fractionations and patient withdrawals across the two cohorts due to adverse events
timeFrame: Months 6, 12
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Toronto General Hospital - Multi Organ Transplant Program
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: George Therapondos, MD
role: PRINCIPAL_INVESTIGATOR
References: