A Prospective Study on the Tolerability and Efficacy of the de Novo Use of Myfortic in Liver Transplant Recipients

March 8, 2017 updated by: Roberto Lopez, MD, University of Pittsburgh
The objective of this study is to compare the safety and efficacy of Myfortic with CellCept in liver transplant patients. Myfortic and CellCept are both immunosuppressive (anti-rejection) drugs. CellCept is commonly used after liver transplantation but gastrointestinal (GI) side effects are very common, sometimes necessitating in its discontinuation. Myfortic is a new drug similar to CellCept, except it is enteric-coated. Our hypothesis is that Myfortic has less GI side effects than CellCept and also has comparable effectiveness to CellCept.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a prospective, randomized, double-blinded, single center, safety and efficacy study comparing Myfortic with CellCept used after liver transplantation. Patients with biopsy-proven acute cellular rejection, renal insufficiency (i.e. acute or chronic renal failure requiring hemodialysis or patients with creatinine clearance < 50 ml/min), or calcineurin inhibitor-induced neurotoxicity (defined as the presence of neurologic symptoms such as tremors, altered mental status, seizures, etc) will be randomized to start on either Myfortic (720 mg po bid) or CellCept (1 gm po bid). In those patients with calcineurin-induced neurotoxicity or nephrotoxicity, tacrolimus or cyclosporine doses will also be reduced to maintain serum trough levels of 4-8 mg/dl or 100-200 mg/dl, respectively.

Comparison: Thirty patients will be enrolled and randomized in this two-armed, double-blinded study- half of the patients will receive Myfortic and the other half, CellCept.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • ALL patients will be adult liver transplant recipients, males or females, 18-80 years of age.
  • Patients must be 30 to 180 days (1 to 6 months) post-transplant to be eligible.
  • Patients currently receiving tacrolimus or cyclosporine with or without corticosteroids as part of their immunosuppressive regimen.
  • Patients with renal insufficiency (history of renal insufficiency or renal failure in the past, patients on hemodialysis, patients with a rising creatinine post-transplant).
  • Patients with biopsy-proven acute cellular rejection (mild, moderate, or severe based on Rejection Activity Index (RAI) as graded by pathologists at UPMC) or repeated bouts of rejection (greater than 2 episodes within a 30 day period).
  • Patients with tacrolimus- or cyclosporine-induced neurotoxicity.
  • Females of childbearing potential must have a negative serum pregnancy test prior to the inclusion period.

Exclusion Criteria:

  • Multi-organ transplant patients.
  • HIV positive patients.
  • Living-related liver transplant recipients
  • Pregnant patients and nursing mothers.
  • Patients with a history of extra-hepatic malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin.
  • Patients with thrombocytopenia (<50,000/mm3), with an absolute neutrophil count of <1,000/mm3 and/or leukocytopenia (<2,000/mm3), and/or hemoglobin <7.0 g/dL prior to enrollment.
  • Presence of clinically significant infection requiring continued therapy, severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus.
  • Evidence of drug and/or alcohol abuse.
  • Decisionally impaired subjects who are not medically or mentally capable of providing consent themselves

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Myfortic Group
Subjects in the Myfortic arm will receive Myfortic 360mg or 720 mg BID for 90 days
Drug: Myfortic
Myfortic 360mg or 720 mg BID for 90 days
Active Comparator: CellCept Group
Subjects in the CellCept arm will receive CellCept 500mg or 1000mg BID for 90 days
Drug: CellCept
CellCept 500mg or 1000mg BID for 90 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil
Time Frame: screening, 2, 6 and 12 weeks

The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation).

The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. The total GSRS range of scores is 15 to 105 with higher scores meaning the worst of symptoms.
screening, 2, 6 and 12 weeks
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil (Abdominal Pain Subscale)
Time Frame: screening, 2, 6 and 12 weeks

The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation).

The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms.

The abdominal Pain subscale range is 3 to 21 with higher scores means worst symptoms
screening, 2, 6 and 12 weeks
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil (Reflux Subscale)
Time Frame: screening, 2, 6 and 12 weeks

The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation).

The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms.

Reflux subscale range is 2 to 14 with higher scores means worst symptoms
screening, 2, 6 and 12 weeks
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Indigestion Subscale)
Time Frame: screening, 2, 6 and 12 weeks

The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation).

The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms.

The Indigestion subscale range is 4 to 28 with higher scores means worst symptoms
screening, 2, 6 and 12 weeks
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Diarrhea Subscale)
Time Frame: screening, 2, 6 and 12 weeks

The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation).

The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms.

The Diarrhea subscale range is 3 to 21 with higher scores means worst symptoms
screening, 2, 6 and 12 weeks
GI Side Effects as Assessed by Gastro Intestinal Symptoms Rating Scale (GSRS) of Enteric-coated Mycophenolate Sodium vs Mycophenolate Mofetil ( Constipation Subscale)
Time Frame: screening, 2, 6 and 12 weeks

The GSRS contains 15 items, each rated on a seven-point Likert scale from no discomfort to very severe discomfort. Based on a factor analysis, the 15 GSRS items break down into the following five scale: abdominal pain syndrome ( abdominal pain, hunger pains, and nausea); reflux syndrome (heartburn and acid regurgitation), diarrhea syndrome (diarrhea, loose stools and urgent need for defecation), indigestion syndrome (borborygmus, abdominal distension, eructation and increased flatus) and constipation syndrome (constipation, hard stools, and feeling of incomplete evacuation).

The GSRS is a disease-specific instrument of 15 items combined into five symptom clusters depicting Reflux, Abdominal pain, Indigestion, Diarrhea, and Constipation. The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms.

Constipation subscale range is 3 to 21 with higher scores means worst symptoms
screening, 2, 6 and 12 weeks
Number of Participants With Bone Marrow Suppression
Time Frame: 12 weeks
Number of participants with: Thrombocytopenia (<50,000 mm3), Leukopenia (< 2000 mm3), absolute neutrophils count ( <1000 mm3) or hemoglobin ( < 7.0 g/dL)
12 weeks
Incidence of Cytomegalovirus Infection or Disease During the Study Period
Time Frame: 12 weeks
number of participants
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Drug Discontinuation Due to Side Effects
Time Frame: 12 weeks
Drug discontinuation due to drug side effects regarding Cellcept and Myfortic.
12 weeks
Number of Participants With Clinically Significant Decrease in Serum Creatinine From Baseline Through Week 12
Time Frame: 12 weeks
Creatinine levels
12 weeks
Number of Participants With Neurotoxicity
Time Frame: 12 weeks
12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Graft Loss or Death During the Study Period
Time Frame: 12 weeks
number of patients
12 weeks
Incidence of Biopsy-proven Acute Cellular Rejection During the Study Period
Time Frame: 12 weeks
number of patients with ACR
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2006

Primary Completion (Actual)

November 1, 2008

Study Completion (Actual)

November 1, 2008

Study Registration Dates

First Submitted

June 12, 2006

First Submitted That Met QC Criteria

June 12, 2006

First Posted (Estimate)

June 14, 2006

Study Record Updates

Last Update Posted (Actual)

March 9, 2017

Last Update Submitted That Met QC Criteria

March 8, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CERL080A-US26

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe