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A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on...

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Autores principales: Suemori, Koichiro, Saijo, Masayuki, Yamanaka, Atsushi, Himeji, Daisuke, Kawamura, Masafumi, Haku, Takashi, Hidaka, Michihiro, Kamikokuryo, Chinatsu, Kakihana, Yasuyuki, Azuma, Taichi, Takenaka, Katsuto, Takahashi, Toru, Furumoto, Akitsugu, Ishimaru, Toshiyuki, Ishida, Masayuki, Kaneko, Masahiko, Kadowaki, Norimitsu, Ikeda, Kenichi, Sakabe, Shigetoshi, Taniguchi, Tomohiro, Ohge, Hiroki, Kurosu, Takeshi, Yoshikawa, Tomoki, Shimojima, Masayuki, Yasukawa, Masaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899362/
https://www.ncbi.nlm.nih.gov/pubmed/33617533
http://dx.doi.org/10.1371/journal.pntd.0009103
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author Suemori, Koichiro
Saijo, Masayuki
Yamanaka, Atsushi
Himeji, Daisuke
Kawamura, Masafumi
Haku, Takashi
Hidaka, Michihiro
Kamikokuryo, Chinatsu
Kakihana, Yasuyuki
Azuma, Taichi
Takenaka, Katsuto
Takahashi, Toru
Furumoto, Akitsugu
Ishimaru, Toshiyuki
Ishida, Masayuki
Kaneko, Masahiko
Kadowaki, Norimitsu
Ikeda, Kenichi
Sakabe, Shigetoshi
Taniguchi, Tomohiro
Ohge, Hiroki
Kurosu, Takeshi
Yoshikawa, Tomoki
Shimojima, Masayuki
Yasukawa, Masaki
author_facet Suemori, Koichiro
Saijo, Masayuki
Yamanaka, Atsushi
Himeji, Daisuke
Kawamura, Masafumi
Haku, Takashi
Hidaka, Michihiro
Kamikokuryo, Chinatsu
Kakihana, Yasuyuki
Azuma, Taichi
Takenaka, Katsuto
Takahashi, Toru
Furumoto, Akitsugu
Ishimaru, Toshiyuki
Ishida, Masayuki
Kaneko, Masahiko
Kadowaki, Norimitsu
Ikeda, Kenichi
Sakabe, Shigetoshi
Taniguchi, Tomohiro
Ohge, Hiroki
Kurosu, Takeshi
Yoshikawa, Tomoki
Shimojima, Masayuki
Yasukawa, Masaki
author_sort Suemori, Koichiro
collection PubMed
description Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7–14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS.
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spelling pubmed-78993622021-03-02 A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome Suemori, Koichiro Saijo, Masayuki Yamanaka, Atsushi Himeji, Daisuke Kawamura, Masafumi Haku, Takashi Hidaka, Michihiro Kamikokuryo, Chinatsu Kakihana, Yasuyuki Azuma, Taichi Takenaka, Katsuto Takahashi, Toru Furumoto, Akitsugu Ishimaru, Toshiyuki Ishida, Masayuki Kaneko, Masahiko Kadowaki, Norimitsu Ikeda, Kenichi Sakabe, Shigetoshi Taniguchi, Tomohiro Ohge, Hiroki Kurosu, Takeshi Yoshikawa, Tomoki Shimojima, Masayuki Yasukawa, Masaki PLoS Negl Trop Dis Research Article Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7–14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS. Public Library of Science 2021-02-22 /pmc/articles/PMC7899362/ /pubmed/33617533 http://dx.doi.org/10.1371/journal.pntd.0009103 Text en © 2021 Suemori et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Suemori, Koichiro
Saijo, Masayuki
Yamanaka, Atsushi
Himeji, Daisuke
Kawamura, Masafumi
Haku, Takashi
Hidaka, Michihiro
Kamikokuryo, Chinatsu
Kakihana, Yasuyuki
Azuma, Taichi
Takenaka, Katsuto
Takahashi, Toru
Furumoto, Akitsugu
Ishimaru, Toshiyuki
Ishida, Masayuki
Kaneko, Masahiko
Kadowaki, Norimitsu
Ikeda, Kenichi
Sakabe, Shigetoshi
Taniguchi, Tomohiro
Ohge, Hiroki
Kurosu, Takeshi
Yoshikawa, Tomoki
Shimojima, Masayuki
Yasukawa, Masaki
A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome
title A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome
title_full A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome
title_fullStr A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome
title_full_unstemmed A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome
title_short A multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome
title_sort multicenter non-randomized, uncontrolled single arm trial for evaluation of the efficacy and the safety of the treatment with favipiravir for patients with severe fever with thrombocytopenia syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7899362/
https://www.ncbi.nlm.nih.gov/pubmed/33617533
http://dx.doi.org/10.1371/journal.pntd.0009103
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