Study of Gastrointestinal Side Effects in African American Kidney Transplant Recipients Treated With CellCept or Myfortic

This study has been terminated.
(enrollment halted in order to have all patients complete follow-up by Jan 2011)
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by:
University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00522548
First received: August 27, 2007
Last updated: February 18, 2011
Last verified: February 2011
  Purpose

Myfortic (enteric-coated mycophenolate sodium) has been shown to have similar effectiveness to CellCept (mycophenolate mofetil) in preventing rejection in kidney transplant recipients. However, Myfortic has been thought to possibly be associated with fewer gastrointestinal side effects. CellCept and Myfortic pharmacokinetics (how the drug is absorbed and broken down) have not been well-studied in African American kidney transplant recipients. The investigators are interested in studying Myfortic and CellCept pharmacokinetics and gastrointestinal side effects in African American kidney transplant recipients.


Condition Intervention Phase
Kidney Transplantation
Drug: Myfortic (enteric coated mycophenolate sodium)
Drug: CellCept (Mycophenolate mofetil)
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IV Randomized, Open Label, Comparative, Single Center Study to Assess Gastrointestinal Adverse Effect Outcomes of De Novo African American Kidney Transplant Recipients Treated With Prograf (Tacrolimus) or Its Generic Equivalent/CellCept (Mycophenolate Mofetil) or Its Generic Equivalent/Corticosteroids Versus Prograf (Tacrolimus) or Its Generic Equivalent/Myfortic (Enteric Coated Mycophenolate Sodium)/Corticosteroids

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Evaluate gastrointestinal toxicity defined as requirement of permanent dose decrease or discontinuation of Myfortic or CellCept related to gastrointestinal toxicity [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluate the pharmacokinetics of CellCept or Myfortic in a sub-set of patients [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Evaluate the incidence of the requirement of full dose proton pump inhibitors [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Evaluate the incidence of intolerance (defined as transient dose reduction or transient discontinuation of Myfortic or CellCept therapy) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Compare Gastrointestinal Symptom Rating Scale (GSRS) score changes from baseline to 24 weeks post-transplant [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Evaluate the incidence of the occurrence of upper and lower gastrointestinal symptoms (further details of definitions are provided by research center) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Evaluate the incidence of rejection [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Compare changes from baseline serum creatinine and Modification of Diet and Renal Disease (MDRD) measured glomerular filtration rates to 24 weeks post-transplant [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 37
Study Start Date: March 2007
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Myfortic Comparator Group
Patients in this group will receive Thymoglobulin (rabbit anti-thymocyte globulin) induction immunosuppression in combination with Myfortic (enteric-coated mycophenolate sodium), Prograf (tacrolimus) or its generic equivalent and corticosteroid immunosuppression
Drug: Myfortic (enteric coated mycophenolate sodium)
Patients in this group will receive Thymoglobulin (rabbit Anti-thymocyte globulin) induction immunosuppression, in combination with Myfortic (enteric-coated mycophenolate sodium, Prograf (tacrolimus) or its generic equivalent and corticosteroid immunosuppression.
Active Comparator: CellCept Comparator group
Patients in this group will receive Thymoglobulin (rabbit anti-thymocyte globulin) induction immunosuppression in combination with CellCept (mycophenolate mofetil) or its generic equivalent, Prograf (tacrolimus) or its generic equivalent and corticosteroid immunosuppression.
Drug: CellCept (Mycophenolate mofetil)
Patients in this group will receive Thymoglobulin (rabbit Anti-thymocyte globulin) induction immunosuppression, in combination with CellCept (mycophenolate mofetil) or its generic equivalent, Prograf (tacrolimus) or its generic equivalent and corticosteroid immunosuppression.

Detailed Description:

African American patients often experience more gastrointestinal complications after kidney transplant than Caucasian patients. In addition, African American kidney transplant recipients also experience a higher incidence of acute rejection and have worse outcomes compared with all other ethnic groups. Reasons accounting for these differences are not well understood.

In light of the increased risk of GI complications in African American patients, we will compare in a pilot study, different regimens (described below) that we commonly use in our clinical practice in this population. As part of this study, patients will also fill out a GSRS survey at specified time points to help describe gastrointestinal side effects after transplant.

Pharmacokinetic studies (studies looking at how the drugs are absorbed and broken down) for Cellcept or Myfortic have largely been performed in Caucasian populations. There is little information available in African-American patients. This is particularly concerning in the face of the worst clinical outcomes observed after transplantation in African American kidney transplant recipients.

Comparisons: Patients will be randomized to one of two groups

  • Group 1: Myfortic (enteric-coated mycophenolate sodium) in combination with Prograf (tacrolimus) or its generic equivalent and corticosteroids
  • Group 2: CellCept (mycophenolate mofetil) or its generic equivalent in combination with Prograf (tacrolimus) or its generic equivalent and corticosteroids

Since toxicity of Cellcept and Myfortic may be influenced by pharmacokinetics (studies that look at how the drugs are absorbed and broken down) of these respective drugs, we will compare the pharmacokinetics of Myfortic and CellCept in a subset of patients. This pharmacokinetic data may have the additional valuable benefit of helping to optimize dosing parameters for Cellcept and Myfortic in African American kidney transplant patients in the future.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recipients of a deceased donor or living donor kidney transplant
  • Recipients of age greater than 18 years but less than 76 years
  • African Americans (self-reported patients of Black African descent who live in the United States)
  • Willingness to participate in a randomized, clinical trial, as indicated by signed informed consent
  • Patients with a history of gastrointestinal complications including any of the following: a history of diarrhea, constipation, acid reflux, or abdominal pain as reported by the patient
  • For women of childbearing age, effective contraception must be used before beginning CellCept or Myfortic, during therapy and 6 weeks after therapy has been discontinued (childbearing women should have a negative serum or urine pregnancy test within 1 week prior to starting CellCept or Myfortic therapy)

Exclusion Criteria:

  • Recipients with any prior solid organ transplant (including kidney)
  • Recipients receiving a concurrent solid organ (heart, liver, pancreas) or cell (islet, bone marrow, stem cell) transplant
  • Recipient age is less than 18 years old or greater than 75 years old
  • Recipients who are not African American (self-reported patients of Black African descent who live in the United States)
  • Recipients on proton pump inhibitor therapy at the time of initial screening (pre-transplant to 2 days post-transplant)
  • Recipients with a gastrointestinal bleed within the past three months
  • Recipients who are pregnant or breast feeding
  • Recipients with known human immunodeficiency virus (HIV) infection
  • Allergy to any of the immunosuppressant medications
  • Concurrent investigational medication
  • Any medical or psychosocial condition, which, in the opinion of the investigators, would hinder compliance with the study requirements
  • Inability or unwillingness of patient to provide informed consent
  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: NCT00522548

Locations
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4322
Sponsors and Collaborators
University of Pennsylvania
Novartis Pharmaceuticals
Investigators
Principal Investigator: Roy Bloom, MD University of Pennsylvania-Renal Electrolyte and Hypertension Division
  More Information

No publications provided

Responsible Party: Roy Bloom, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00522548     History of Changes
Other Study ID Numbers: CERL080A-US49
Study First Received: August 27, 2007
Last Updated: February 18, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
African American
Kidney Transplant

Additional relevant MeSH terms:
Tacrolimus
Mycophenolate mofetil
Antilymphocyte Serum
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014