Trial Comparing Immediate Versus Extended Release Tacrolimus; Reducing Calcineurin Inhibitor Related Toxicity in Lung Transplantation Patients

Summary

Lung transplantation is a life-saving option in patients with end-stage lung disease. The introduction of calcineurin inhibitors has significantly improved long-term outcome in lung transplantation. The most frequently used calcineurin inhibitor as maintenance therapy is immediate release tacrolimus, dosed twice daily, which has shown to reduce both acute and chronic rejection. However, a drawback to the administration of tacrolimus is its toxicity. Especially progressive renal toxicity, new onset diabetes and hypertension contribute to the high cardiovascular burdon in this patient group. Since a few years an once daily extended release tacrolimus has been introduced in solid organ transplantation. The advantage of extended release tacrolimus is its prolonged release and higher bioavailability than other tacrolimus formulations. This result in lower peaks, more stable serum levels over 24 hours, and less fluctuation of blood concentrations. Long-term toxicity outcome of extended release tacrolimus after lung transplantation has not been studied so far. Therefore the potential benefit of exteded release tacrolimus in de novo and stable post-lung transplant recipients should be investigated.

Timeline

Start

2020-07-28

Primary completion

2024-08-01

Completion

2024-08-01

Publications

• Results Sintes H, Saez-Gimenez B, Berastegui C, Lopez-Meseguer M, Monforte V, Bravo C, Vima J, Gomez-Olles S, Roman A. Pharmacokinetic Study of Conversion Between 2 Formulations of Once-daily Extended-release Tacrolimus in Stable Lung Transplant Patients. Transplantation. 2018 Oct;102(10):e439-e446. doi: 10.1097/TP.0000000000002348.
• Results Mendez A, Berastegui C, Lopez-Meseguer M, Monforte V, Bravo C, Blanco A, Camos S, Pou L, Roman A. Pharmacokinetic study of conversion from tacrolimus twice-daily to tacrolimus once-daily in stable lung transplantation. Transplantation. 2014 Feb 15;97(3):358-62. doi: 10.1097/01.TP.0000435699.69266.66.
• Results TruneCka P, Klempnauer J, Bechstein WO, Pirenne J, Friman S, Zhao A, Isoniemi H, Rostaing L, Settmacher U, Monch C, Brown M, Undre N, Tisone G; DIAMONDdagger study group. Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens-The DIAMOND Study. Am J Transplant. 2015 Jul;15(7):1843-54. doi: 10.1111/ajt.13182. Epub 2015 Feb 23.
• Results Sanchez Fructuoso A, Ruiz JC, Franco A, Diekmann F, Redondo D, Calvino J, Serra N, Aladren MJ, Cigarran S, Manonelles A, Ramos A, Gomez G, Gonzalez Posada JM, Andres A, Beneyto I, Muniz AL, Perello M, Lauzurica R. Effectiveness and safety of the conversion to MeltDose(R) extended-release tacrolimus from other formulations of tacrolimus in stable kidney transplant patients: A retrospective study. Clin Transplant. 2020 Jan;34(1):e13767. doi: 10.1111/ctr.13767. Epub 2019 Dec 31.

Drugs

Indications

No indication recorded.