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Efficacy of Prolonged- and Immediate-release Tacrolimus in Kidney Transplantation: A Pooled Analysis of Two Large, Randomized, Controlled Trials.
- Source :
-
Transplantation proceedings [Transplant Proc] 2017 Nov; Vol. 49 (9), pp. 2040-2049. - Publication Year :
- 2017
-
Abstract
- Background: Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy).<br />Methods: Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, BCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction). The 95% confidence intervals were calculated (10% noninferiority margin).<br />Results: Overall, 633 patients received prolonged-release tacrolimus (12-03, n = 331; OSAKA, n = 302) and 645 received immediate-release tacrolimus (n = 336; n = 309). Baseline characteristics were comparable. Proportionately more patients receiving prolonged-release tacrolimus had trough levels of 5-15 ng/mL on day 1 (60.8%) and 2 (56.6%) versus immediate-release tacrolimus (42.5% and 43.9%, respectively, both P < .001). Efficacy of prolonged-release and immediate-release tacrolimus were similar as assessed by BCAR (13.9% vs 14.1%, respectively), European Medicines Agency composite endpoint (40.3% vs 38.3%) and US Food and Drug Administration composite endpoint (21.5% vs 19.8%).<br />Conclusions: Novel efficacy endpoints as required by the European Medicines Agency and US Food and Drug Administration demonstrate noninferiority of prolonged-release versus immediate-release tacrolimus. Significantly more patients treated with prolonged-release tacrolimus versus immediate-release tacrolimus achieved trough levels of 5 to 15 ng/mL early after transplantation. ClinicalTrials.govNCT00189839; NCT00717470.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Adrenal Cortex Hormones administration & dosage
Adult
Databases, Factual
Delayed-Action Preparations
Drug Therapy, Combination
Female
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Mycophenolic Acid therapeutic use
Prospective Studies
Randomized Controlled Trials as Topic
Treatment Failure
Graft Rejection prevention & control
Immunosuppressive Agents administration & dosage
Kidney Transplantation
Tacrolimus administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2623
- Volume :
- 49
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Transplantation proceedings
- Publication Type :
- Academic Journal
- Accession number :
- 29149958
- Full Text :
- https://doi.org/10.1016/j.transproceed.2017.07.011