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Efficacy and safety of prolonged-release tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus - a Phase 2, open-label, single-arm, one-way crossover study

J. Rubik, D. Debray, D. Kelly, F. Iserin, NJA. Webb, P. Czubkowski, K. Vondrak, AL. Sellier-Leclerc, C. Rivet, S. Riva, B. Tönshoff, L. D'Antiga, SD. Marks, R. Reding, G. Kazeem, N. Undre,

. 2019 ; 32 (11) : 1182-1193. [pub] 20190827

Jazyk angličtina Země Velká Británie

Typ dokumentu klinické zkoušky, fáze II, časopisecké články, multicentrická studie

Perzistentní odkaz   https://www.medvik.cz/link/bmc20023570

Grantová podpora
Astellas Pharma Europe
NIHR Manchester Clinical Research Facility

There are limited clinical data regarding prolonged-release tacrolimus (PR-T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR-T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate-release tacrolimus (IR-T), on a 1:1 mg total-daily-dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy-confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole-blood trough levels (target 3.5-15 ng/ml) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6-17.7% of patients across follow-up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug-related treatment-emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR-T to PR-T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.

Astellas Pharma Europe Ltd Chertsey UK

BENKAZ Consulting Ltd Cambridge UK Astellas Pharma Europe Ltd Chertsey UK

Department of Gastroenterology Hepatology Nutritional Disturbances and Pediatrics The Children's Memorial Health Institute Warsaw Poland

Department of Nephrology Kidney Transplantation and Hypertension The Children's Memorial Health Institute Warsaw Poland

Department of Nephrology Rheumatology and Dermatology Center for Rare Diseases Civil Hospice of Lyon 'Woman Mother Child' Hospital Bron Cedex France

Department of Pediatric Nephrology Great Ormond Street Hospital for Children NHS Foundation Trust London UK

Department of Pediatric Nephrology NIHR Wellcome Trust Manchester Clinical Research Facility Manchester Academic Health Science Centre Royal Manchester Children's Hospital University of Manchester Manchester UK

Department of Pediatrics 1 University Children's Hospital Heidelberg Heidelberg Germany

Department of Pediatrics 2nd School of Medicine University Hospital Motol Charles University Prague Czech Republic

Department of Pediatrics ISMETT IRCCS Palermo Italy

Pediatric Cardiology Unit APHP Hôpital Universitaire Necker Paris France

Pediatric Hepatology Gastroenterology and Transplantation Civil Hospice of Lyon Lyon France

Pediatric Hepatology Gastroenterology and Transplantation Hospital Papa Giovanni XXIII Bergamo Italy

Pediatric Hepatology Unit APHP Hôpital Universitaire Necker Paris France

The Liver Unit Birmingham Women's and Children's Hospital Birmingham UK

Unité de Chirurgie et Transplantation Pédiatrique Cliniques Universitaires Saint Luc Université Catholique de Louvain Brussels Belgium

Citace poskytuje Crossref.org

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