Randomized Trial Comparing Late Concentration-controlled Calcineurin Inhibitor or Mycophenolate Mofetil Withdrawal.
Mourer JS, Hartigh J, et al.Transplantation, 93(9): 887-894, 2012.
Aims
To explore whether late concentration-controlled withdrawal of a calcineurin inhibitor (CNI) or mycophenolate mofetil (MMF) would reduce the risk of acute rejection in renal transplant recipients.
Interventions
Initial triple immunosuppression therapy consisted of a CNI, MMF and steroids for at least 6 months post-transplantation. At 6 months patients were randomized to continuation of triple therapy versus concentration-controlled MMF-withdrawal (target area under the time-concentration curve (AUC) for cyclosporine was 3250 ng•hr/mL and 120 ng•hr/mL for tacrolimus:) versus CNI-withdrawal (AUC for mycophenolic acid was 75 µg•hr/mL).
Participants
177 stable renal transplant recipients.
Outcomes
Primary outcome was change in creatinine clearance and estimated glomerular filtration rate after 3 years. Secondary outcomes included the number and severity of acute rejection episodes, chronic transplant dysfunction, patient and graft survival rates, blood pressure, serum lipids profile, hematologic parameters, malignancies, infections and adverse events.
Follow-up
3 years
CET Conclusions
This well conducted single centre RCT suggests that patients on triple therapy comprising a CNI, MMF and steroids after 6 months could have either MMF or CNI withdrawal with no major problems provided the AUC of MMF was monitored. There was improvement in renal function, which was maintained up to three years, in those patients who had had CNI withdrawal.
Data analysis
Modified intention-to-treat analysis
Trial registration
ISRCTN81895822 (ISRCTN)