Intensified Dosing of Cellcept (Mycophenolate Mofetil) in Kidney Transplantation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Capital District Health Authority, Canada
ClinicalTrials.gov Identifier:
NCT00943228
First received: July 6, 2009
Last updated: August 8, 2012
Last verified: August 2012
  Purpose

The primary objective of this study is to determine whether 4 grams daily of mycophenolate mofetil (MMF) results in a greater proportion of individuals adequately exposed as measured by drug levels (area under the curve of > 40 mg*hr/L).


Condition Intervention Phase
Acute Rejection of Renal Transplant
Drug: mycophenolate mofetil
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Bio-availability Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Intensified Dosing of Cellcept in Kidney Transplantation Trial

Resource links provided by NLM:


Further study details as provided by Capital District Health Authority, Canada:

Primary Outcome Measures:
  • Adequate drug exposure. MPA AUC > 40 mg*hr/l [ Time Frame: First two weeks - 14 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea). [ Time Frame: First two weeks - 14 days ] [ Designated as safety issue: Yes ]
  • Leukopenia, anemia, thrombocytopenia and infection. [ Time Frame: First two weeks - 14 days ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: February 2010
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: mycophenolate mofetil
mycophenolate mofetil 2000mg BID (4g/day) for 14 days, followed by mycophenolate 1000mg BID (2g/day) thereafter
Drug: mycophenolate mofetil
High dose 4gms daily
Other Names:
  • MMF
  • Cellcept

Detailed Description:

Several studies have shown that early exposure to adequate levels of immunosuppression are required to reduce acute rejection rates in kidney transplantation.(1, 2) Our center has shown that early exposure of mycophenolate mofetil (MMF or Cellcept) is associated with acute rejection rates and that many patients are underexposed in the early transplant period.(2) In a recently completed multicenter Canadian (CLEAR) study we found that higher doses of mycophenolate mofetil (MMF 3 grams daily versus 2 grams daily) were associated with better early exposure by day 5 and that this was associated with less rejection but no increase in toxicity.(3) The best cut point that discriminated between low and high rejection rates was a mycophenolic acid (MPA) 12 hour area under the curve (AUC) of 40 mg*hr/L. Patients below this level experienced rejection rates of 50% compared to <16% for those above this level. Even with the higher dose 26% of subjects were inadequately exposed. Since medication adjustments based on drug levels is hampered by steady state conditions and the turn around time of MPA testing we are interested in exploring even higher initial doses of MMF with the aim to maximize the numbers of patients achieving adequate early exposure to MPA.

Objectives:

The primary objective of this study is to determine whether 4 gms daily of MMF results in a greater proportion of individuals adequately exposed as measured by a day 5 MPA AUC of >40 mg*hr/L.

The secondary objectives of this study are to assess the ability of this strategy to achieve target MPA AUC exposure of 40-60 mg*hr/L by day 14 and to determine the distribution of MMF doses that are necessary to achieve this level of exposure. Safety data (hemoglobin and WBC counts, need for further dose changes based on gastrointestinal intolerance, acute rejection, renal function, and wound infection) will be also collected over the first 3 months post transplantation.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients undergoing single organ kidney transplantation.
  • Age > 18 years old.
  • Patients who would normally receive our standard therapy of basiliximab, tacrolimus, MMF and steroids.
  • All patients will be required to sign informed consent.

Exclusion Criteria:

  • Patients will be excluded if they require anti-thymocyte induction therapy, have documented gastroparesis, have known intolerance to MMF, or are prescribed cyclosporine.
  • As a standard policy all women of childbearing age will be informed about the risks of all immunosuppressive drugs on fetal outcomes and will be required to use 2 forms of birth control.
  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: NCT00943228

Locations
Canada, Nova Scotia
QE II Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Sponsors and Collaborators
Capital District Health Authority, Canada
Investigators
Principal Investigator: Bryce A Kiberd, MD Dalhousie University
  More Information

No publications provided by Capital District Health Authority, Canada

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Capital District Health Authority, Canada
ClinicalTrials.gov Identifier: NCT00943228     History of Changes
Other Study ID Numbers: IDOC001
Study First Received: July 6, 2009
Last Updated: August 8, 2012
Health Authority: Canada: Health Canada

Keywords provided by Capital District Health Authority, Canada:
Renal transplantation
Adequate exposure
Acute rejection
mycophenolate mofetil
immunosuppression

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

ClinicalTrials.gov processed this record on October 23, 2014