Intensified Dosing of Cellcept (Mycophenolate Mofetil) in Kidney Transplantation

Acute Rejection of Renal Transplant Clinical Trial

Official title:

Intensified Dosing of Cellcept in Kidney Transplantation Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00943228
• Other study ID #: IDOC001
• Status: Completed
• Phase: Phase 4
• First received: July 6, 2009
• Last updated: August 8, 2012
• Start date: February 2010
• Est. completion date: February 2012

Study information

• Verified date: August 2012
• Source: Nova Scotia Health Authority
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Bio-availability Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Acute Rejection of Renal Transplant

Intervention

Drug:
• mycophenolate mofetil
High dose 4gms daily

Locations

Country	Name	City	State
Canada	QE II Health Sciences Centre	Halifax	Nova Scotia

Sponsors (1)

Lead Sponsor	Collaborator
Nova Scotia Health Authority

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adequate drug exposure. MPA AUC > 40 mg*hr/l		First two weeks - 14 days	No
Secondary	Gastrointestinal symptoms (nausea, vomiting, abdominal pain, diarrhea).		First two weeks - 14 days	Yes
Secondary	Leukopenia, anemia, thrombocytopenia and infection.		First two weeks - 14 days	Yes