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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Japan
2018
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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. |
format | Online Article Text |
id | pubmed-6349796 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Springer Japan |
record_format | MEDLINE/PubMed |
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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