Novel once-daily extended-release tacrolimus (LCPT) versus twice-daily tacrolimus in de novo kidney transplants: one-year results of Phase III, double-blind, randomized trial
K Budde, S Bunnapradist, J M Grinyo, K Ciechanowski, J E Denny, H T Silva, L Rostaing, Envarsus study group, Jason E Denny, Sanjay Kulkarni, Donald Hricik, Barbara A Bresnahan, Suphamai Bunnapradist, Rafik A El-Sabrout, Laurence K Chan, Gaetano Ciancio, Mohamed A El-Ghoroury, Michael J Goldstein, Robert S Gaston, Reginald Y Gohh, Mary T Killackey, Anne King, Richard J Knight, Arputharaj H Kore, Debra L Sudan, Javier Chapochnick Friedmann, Shamkant P Mulgaonkar, Charles Nolan, Oleh G Pankewycz, John D Pirsch, Heidi M Schaefer, Steven M Steinberg, Bruce E Gelb, Karin A True, Patricia M West-Thielke, Mary M Waybill, Joshua H Wolf, Beverley L Ketel, Robert C Harland, Fuad S Shihab, Elisabeth Cassuto, Yannick Le Meur, Lionel Rostaing, Christophe Mariat, Josep Maria Grinyó, Jose Puig, Daniel Seron, Giuseppe Tisone, Kazimierz Ciechanowski, Bartosz Foroncewicz, Zbigniew Wlodarczyk, Klemens Budde, Oliver Witzke, Guillermo A Mondragon, Eduardo Mancilla Urrea, Josefina Alberu Gomez, Rafael Reyes Acevedo, Maria del Carmen Rial, Pablo A Novoa, Helio T Silva Junior, Valter D Garcia, Deise D Carvalho, Luciana T Santamaria Saber, Fabiana L Contieri, Marcos G Bastos, Roberto C Manfro, John Kanellis, Josette Eris, Philip O'Connell, Peter Hughes, Graeme Russ, Grant B Pidgeon, Ian D Dittmer, Terence Kee, Anantharaman Vathsala, Radomir Naumovic, Igor Mitic, Parmjeet Randhawa, K Budde, S Bunnapradist, J M Grinyo, K Ciechanowski, J E Denny, H T Silva, L Rostaing, Envarsus study group, Jason E Denny, Sanjay Kulkarni, Donald Hricik, Barbara A Bresnahan, Suphamai Bunnapradist, Rafik A El-Sabrout, Laurence K Chan, Gaetano Ciancio, Mohamed A El-Ghoroury, Michael J Goldstein, Robert S Gaston, Reginald Y Gohh, Mary T Killackey, Anne King, Richard J Knight, Arputharaj H Kore, Debra L Sudan, Javier Chapochnick Friedmann, Shamkant P Mulgaonkar, Charles Nolan, Oleh G Pankewycz, John D Pirsch, Heidi M Schaefer, Steven M Steinberg, Bruce E Gelb, Karin A True, Patricia M West-Thielke, Mary M Waybill, Joshua H Wolf, Beverley L Ketel, Robert C Harland, Fuad S Shihab, Elisabeth Cassuto, Yannick Le Meur, Lionel Rostaing, Christophe Mariat, Josep Maria Grinyó, Jose Puig, Daniel Seron, Giuseppe Tisone, Kazimierz Ciechanowski, Bartosz Foroncewicz, Zbigniew Wlodarczyk, Klemens Budde, Oliver Witzke, Guillermo A Mondragon, Eduardo Mancilla Urrea, Josefina Alberu Gomez, Rafael Reyes Acevedo, Maria del Carmen Rial, Pablo A Novoa, Helio T Silva Junior, Valter D Garcia, Deise D Carvalho, Luciana T Santamaria Saber, Fabiana L Contieri, Marcos G Bastos, Roberto C Manfro, John Kanellis, Josette Eris, Philip O'Connell, Peter Hughes, Graeme Russ, Grant B Pidgeon, Ian D Dittmer, Terence Kee, Anantharaman Vathsala, Radomir Naumovic, Igor Mitic, Parmjeet Randhawa
Abstract
This Phase III randomized trial examined efficacy and safety of a novel once-daily extended-release tacrolimus formulation (LCP-Tacro [LCPT]) versus twice-daily tacrolimus in de novo kidney transplantation. Primary efficacy end point was proportion of patients with treatment failure (death, graft failure, biopsy-proven acute rejection or lost to follow-up) within 12 months. Starting doses were, LCPT: 0.17 mg/kg/day and tacrolimus twice-daily: 0.1 mg/kg/day; 543 patients were randomized, LCPT: n = 268; tacrolimus twice-daily: n = 275. At 12 months treatment failure was LCPT: 18.3% and tacrolimus twice-daily: 19.6%; the upper 95% CI of the treatment difference was +5.27%, below the predefined +10% noninferiority criteria. There were no significant differences in the incidence of individual efficacy events or adverse events. Target tacrolimus trough levels were more rapidly achieved in the LCPT group. Following initial dose, 36.6% of patients in the LCPT group had rapidly attained trough levels within 6-11 ng/mL versus 18.5% of tacrolimus twice-daily patients; majority of tacrolimus twice-daily patients (74.7%) had troughs <6 ng/mL compared with 33.5% in the LCPT group. Overall, cumulative study dose was 14% lower for LCPT. Results suggest that use of once-daily LCPT in de novo kidney transplantation is efficacious and safe. Lower LCPT dose reflects the improved absorption provided by the novel formulation.
Keywords: calcineurin inhibitor: tacrolimus; clinical research/practice; clinical trial; immunosuppressant; immunosuppression/immune modulation; kidney transplantation/nephrology.
© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.
Source: PubMed