Impact of Once- Versus Twice-Daily Tacrolimus Dosing on Medication Adherence in Stable Renal Transplant Recipients: A Canadian Single-Center Randomized Controlled Trial.

backgroundPrevalence of immunosuppressant nonadherence in renal transplant recipients is high despite negative clinical outcomes associated with nonadherence. Simplification of dosing has been demonstrated to improve adherence in renal transplant recipients as measured through electronic monitoring and self-report.

objectiveThe purpose of this study was to replicate and extend previous findings by measuring adherence with multiple methods in a Canadian sample.

designThe study design was a randomized controlled medication dosing trial in adult renal transplant patients. The trial length was 4 months.

settingThis study was conducted within the Solid Organ Transplant (SOT) Clinic at Vancouver General Hospital (VGH; Vancouver, Canada). PATIENTS: A total of 46 adult renal recipients (at least 1 year post-transplant) were recruited through the SOT clinic. With 8 withdrawals, 38 individuals completed all phases of the study. MEASUREMENTS: Medication adherence was measured for a period of 4 months using multiple methods, including electronic monitoring (MEMS [Medication Event Monitoring System]), pharmacy refill data (medication possession ratio [MPR]), and by self-report using the Adherence subscale of the Transplant Effects Questionnaire (TEQ).

methodsParticipants were randomized to twice-daily (n = 19) or once-daily tacrolimus dosing (n = 19) and followed over a 4-month period via monthly clinic study visits. Comparisons between the treatment groups were performed using the Mann-Whitney

resultsAs outlined in Table 3, the once-daily dosing group showed significantly better MEMS Dose Adherence ( LIMITATIONS: Limitations included small sample size and short follow-up period, precluding the examination of clinical outcome differences.

conclusionsResults for dose adherence replicate the finding that dose simplification increases adherence to immunosuppressants as measured through electronic monitoring. Such an advantage for the once-daily dosing group was not seen across the 2 other electronic monitoring measurement variables (days and timing adherence). This study extends previous research by examining adherence in once versus twice-daily dosing via prescription refill data in a Canadian sample. Given the gravity of potential health outcomes associated with nonadherence, although results indicate inconsistencies in significance testing across measurement methods, the medium to large effect sizes seen in the data favoring better adherence with once-daily dosing provide an indication of the potential clinical significance of these findings.

trial registrationThis study was registered with ClinicalTrials.gov (NCT01334333) on April 11, 2011.