Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial.
Rostaing L, Bunnapradist S, et alAmerican Journal of Kidney Diseases 2016; 67(4): 648-659.
Aims
To report the blinded efficacy and safety outcomes at 24months of a phase 3 trial of novel once-daily extended-release Tacrolimus (LCPT) versus twice-daily immediate-release tacrolimus (IR-Tac) in de novo kidney transplant recipients*.
Interventions
Participants were randomly assigned to receive either once daily LCPT tablets (0.17 mg/kg/d), or twice-daily IR-Tac capsules (0.1 mg/kg/d) with subsequent doses of each study drug adjusted to maintain whole-blood trough concentrations within the target range of 6-11 ng/mL for the first 30 days, then 4-11 ng/mL thereafter.
Participants
543 de novo kidney transplant recipients of a living or deceased donor kidney transplant.
Outcomes
The primary outcome measured was the incidence of treatment failures such as death, transplant failure, biopsy-proven acute rejection, or loss to follow-up. Secondary outcomes measured were adverse events (AEs), serious AEs, discontinuation due to AEs, incidence of predefined potentially clinically significant laboratory values, new-onset diabetes after transplantation, posttransplantation lymphoproliferative disorder, glomerular filtration rate, laboratory values and vital signs, opportunistic infections, malignancy and BK virus diseases.
Follow-up
24 months
CET Conclusions
This double-blinded, noninferiority RCT compared the efficacy and safety of once-daily (LCP-Tacro) versus twice-daily tacrolimus in de novo kidney transplant recipients at 24 months and included a subgroup analysis for gender, age and race. Patients received LCP-Tacro or a matching double-dummy placebo and both patients and investigators were blinded up to 24 months. The sample size was adequate to provide 90% power and a non-inferiority margin of 10% was used. LCP-tacro was non-inferior to twice-daily tacrolimus at 12 and 24 months. There were also no significant differences for the subgroups in terms of treatment failure.
Data analysis
Modified intention-to-treat analysis
Quality notes
Previously reported as *Budde K, et al. Once daily LCP-Tacro MeltDose tacrolimus vs. twice daily tacrolimus in de novo kidney transplants: one-year results of phase 3, double-blind, randomized trial. Am J Transplant. 2014;14:2796-2806.
Trial registration
ClinicalTrials.gov - NCT01187953