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A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation

BACKGROUND: Thrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate the efficacy and safety of lusutrombopag for the treatment of thrombocytopenia before percutaneous liver radiofrequency ablation...

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Autores principales: Tateishi, Ryosuke, Seike, Masataka, Kudo, Masatoshi, Tamai, Hideyuki, Kawazoe, Seiji, Katsube, Takayuki, Ochiai, Toshimitsu, Fukuhara, Takahiro, Kano, Takeshi, Tanaka, Katsuaki, Kurokawa, Mineo, Yamamoto, Kazuhide, Osaki, Yukio, Izumi, Namiki, Imawari, Michio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Japan 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349796/
https://www.ncbi.nlm.nih.gov/pubmed/30105510
http://dx.doi.org/10.1007/s00535-018-1499-2
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author Tateishi, Ryosuke
Seike, Masataka
Kudo, Masatoshi
Tamai, Hideyuki
Kawazoe, Seiji
Katsube, Takayuki
Ochiai, Toshimitsu
Fukuhara, Takahiro
Kano, Takeshi
Tanaka, Katsuaki
Kurokawa, Mineo
Yamamoto, Kazuhide
Osaki, Yukio
Izumi, Namiki
Imawari, Michio
author_facet Tateishi, Ryosuke
Seike, Masataka
Kudo, Masatoshi
Tamai, Hideyuki
Kawazoe, Seiji
Katsube, Takayuki
Ochiai, Toshimitsu
Fukuhara, Takahiro
Kano, Takeshi
Tanaka, Katsuaki
Kurokawa, Mineo
Yamamoto, Kazuhide
Osaki, Yukio
Izumi, Namiki
Imawari, Michio
author_sort Tateishi, Ryosuke
collection PubMed
description BACKGROUND: Thrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate the efficacy and safety of lusutrombopag for the treatment of thrombocytopenia before percutaneous liver radiofrequency ablation (RFA) for primary hepatic cancer in patients with CLD. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study conducted in Japan, 61 CLD patients with platelet count < 50 × 10(3)/µL at screening were randomized to placebo or lusutrombopag 2, 3, or 4 mg once daily for 7 days, followed by a 28-day post-treatment assessment period. The primary efficacy endpoint was the proportion of patients who did not require platelet transfusion before RFA. The pre-specified key secondary efficacy endpoint was the proportion of responders. Adverse events (AEs) and thrombosis-related AEs were evaluated. RESULTS: The proportion of patients who did not require platelet transfusion before RFA and that of responders were significantly higher (p < 0.01) in the 2-mg (80.0, 66.7%), 3-mg (81.3, 68.8%), and 4-mg groups (93.3, 80.0%) compared with the placebo group (20.0, 6.7%) and showed a dose-dependent effect. The incidence of AEs was 97.8 and 100% in the lusutrombopag (all groups) and placebo groups, respectively; no dose-related increase was observed. Four patients experienced thrombosis-related events (one each in the placebo and 2-mg groups, and two in the 4-mg group). A total of 16 (18%) adverse drug reactions occurred in the safety analysis set. CONCLUSIONS: Lusutrombopag 3 mg once daily for 7 days was effective without raising concerns about excessive increases in platelet count. CLINICAL TRIAL REGISTRATION: The study is registered at JapicCTI-121944. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00535-018-1499-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-63497962019-02-15 A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation Tateishi, Ryosuke Seike, Masataka Kudo, Masatoshi Tamai, Hideyuki Kawazoe, Seiji Katsube, Takayuki Ochiai, Toshimitsu Fukuhara, Takahiro Kano, Takeshi Tanaka, Katsuaki Kurokawa, Mineo Yamamoto, Kazuhide Osaki, Yukio Izumi, Namiki Imawari, Michio J Gastroenterol Original Article—Liver, Pancreas, and Biliary Tract BACKGROUND: Thrombocytopenia represents an obstacle for invasive procedures in chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose and evaluate the efficacy and safety of lusutrombopag for the treatment of thrombocytopenia before percutaneous liver radiofrequency ablation (RFA) for primary hepatic cancer in patients with CLD. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study conducted in Japan, 61 CLD patients with platelet count < 50 × 10(3)/µL at screening were randomized to placebo or lusutrombopag 2, 3, or 4 mg once daily for 7 days, followed by a 28-day post-treatment assessment period. The primary efficacy endpoint was the proportion of patients who did not require platelet transfusion before RFA. The pre-specified key secondary efficacy endpoint was the proportion of responders. Adverse events (AEs) and thrombosis-related AEs were evaluated. RESULTS: The proportion of patients who did not require platelet transfusion before RFA and that of responders were significantly higher (p < 0.01) in the 2-mg (80.0, 66.7%), 3-mg (81.3, 68.8%), and 4-mg groups (93.3, 80.0%) compared with the placebo group (20.0, 6.7%) and showed a dose-dependent effect. The incidence of AEs was 97.8 and 100% in the lusutrombopag (all groups) and placebo groups, respectively; no dose-related increase was observed. Four patients experienced thrombosis-related events (one each in the placebo and 2-mg groups, and two in the 4-mg group). A total of 16 (18%) adverse drug reactions occurred in the safety analysis set. CONCLUSIONS: Lusutrombopag 3 mg once daily for 7 days was effective without raising concerns about excessive increases in platelet count. CLINICAL TRIAL REGISTRATION: The study is registered at JapicCTI-121944. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00535-018-1499-2) contains supplementary material, which is available to authorized users. Springer Japan 2018-08-13 2019 /pmc/articles/PMC6349796/ /pubmed/30105510 http://dx.doi.org/10.1007/s00535-018-1499-2 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article—Liver, Pancreas, and Biliary Tract
Tateishi, Ryosuke
Seike, Masataka
Kudo, Masatoshi
Tamai, Hideyuki
Kawazoe, Seiji
Katsube, Takayuki
Ochiai, Toshimitsu
Fukuhara, Takahiro
Kano, Takeshi
Tanaka, Katsuaki
Kurokawa, Mineo
Yamamoto, Kazuhide
Osaki, Yukio
Izumi, Namiki
Imawari, Michio
A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation
title A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation
title_full A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation
title_fullStr A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation
title_full_unstemmed A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation
title_short A randomized controlled trial of lusutrombopag in Japanese patients with chronic liver disease undergoing radiofrequency ablation
title_sort randomized controlled trial of lusutrombopag in japanese patients with chronic liver disease undergoing radiofrequency ablation
topic Original Article—Liver, Pancreas, and Biliary Tract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6349796/
https://www.ncbi.nlm.nih.gov/pubmed/30105510
http://dx.doi.org/10.1007/s00535-018-1499-2
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