Intensified Dosing of Cellcept (Mycophenolate Mofetil) in Kidney Transplantation

Intensified Dosing of Cellcept in Kidney Transplantation Trial

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).

Study Overview

• Status: Completed
• Conditions: Acute Rejection of Renal Transplant
• Intervention / Treatment: Drug: mycophenolate mofetil

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • QE II Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: Cellcept; MMF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adequate drug exposure. MPA AUC > 40 mg*hr/l	First two weeks - 14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea).	First two weeks - 14 days
Leukopenia, anemia, thrombocytopenia and infection.	First two weeks - 14 days

Collaborators and Investigators

• Sponsor: Nova Scotia Health Authority
• Investigators: Principal Investigator: Bryce A Kiberd, MD, Dalhousie University

Publications and helpful links

General Publications

• Kiberd BA, Lawen J, Daley C. Limits to intensified mycophenolate mofetil dosing in kidney transplantation. Ther Drug Monit. 2012 Dec;34(6):736-8. doi: 10.1097/FTD.0b013e31826d7bfa.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (ACTUAL): February 1, 2012
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: July 6, 2009
• First Submitted That Met QC Criteria: July 21, 2009
• First Posted (ESTIMATE): July 22, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): August 9, 2012
• Last Update Submitted That Met QC Criteria: August 8, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: immunosuppression; mycophenolate mofetil; Acute rejection; Renal transplantation; Adequate exposure
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: IDOC001