This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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

This study has been completed.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Roberto Lopez, MD, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00336817
First received: June 12, 2006
Last updated: March 8, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention
Immunosuppression Drug: Myfortic Drug: CellCept

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective Study on the Tolerability and Efficacy of the de Novo Use of Myfortic in Liver Transplant Recipients

Resource links provided by NLM:


Further study details as provided by Roberto Lopez, MD, University of Pittsburgh:

Primary Outcome Measures:
  • 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.


  • 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


  • 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


  • 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


  • 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


  • 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


  • 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)

  • Incidence of Cytomegalovirus Infection or Disease During the Study Period [ Time Frame: 12 weeks ]
    number of participants


Secondary Outcome Measures:
  • Drug Discontinuation Due to Side Effects [ Time Frame: 12 weeks ]
    Drug discontinuation due to drug side effects regarding Cellcept and Myfortic.

  • Number of Participants With Clinically Significant Decrease in Serum Creatinine From Baseline Through Week 12 [ Time Frame: 12 weeks ]
    Creatinine levels

  • Number of Participants With Neurotoxicity [ Time Frame: 12 weeks ]

Other Outcome Measures:
  • Incidence of Graft Loss or Death During the Study Period [ Time Frame: 12 weeks ]
    number of patients

  • Incidence of Biopsy-proven Acute Cellular Rejection During the Study Period [ Time Frame: 12 weeks ]
    number of patients with ACR


Enrollment: 30
Study Start Date: November 2006
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00336817

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
Novartis Pharmaceuticals
Investigators
Principal Investigator: Michael E de Vera, MD University of Pittsburgh
  More Information

Responsible Party: Roberto Lopez, MD, Assistant Professor of Surgery, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00336817     History of Changes
Other Study ID Numbers: CERL080A-US26
Study First Received: June 12, 2006
Results First Received: May 23, 2016
Last Updated: March 8, 2017

Keywords provided by Roberto Lopez, MD, University of Pittsburgh:
Liver transplantation
mycophenolate mofetil
gastrointestinal
adverse effects

Additional relevant MeSH terms:
Mycophenolate mofetil
Mycophenolic Acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 21, 2017