Intensified Dosing of Cellcept (Mycophenolate Mofetil) in Kidney Transplantation
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).
Acute Rejection of Renal Transplant
Drug: mycophenolate mofetil
|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|
- Adequate drug exposure. MPA AUC > 40 mg*hr/l [ Time Frame: First two weeks - 14 days ] [ Designated as safety issue: No ]
- 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 ]
|Study Start Date:||February 2010|
|Study Completion Date:||February 2012|
|Primary Completion Date:||February 2012 (Final data collection date for primary outcome measure)|
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
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.
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.
|Canada, Nova Scotia|
|QE II Health Sciences Centre|
|Halifax, Nova Scotia, Canada, B3H 1V7|
|Principal Investigator:||Bryce A Kiberd, MD||Dalhousie University|