PMID- 33617533
OWN - NLM
STAT- MEDLINE
DCOM- 20210611
LR  - 20210611
IS  - 1935-2735 (Electronic)
IS  - 1935-2727 (Print)
IS  - 1935-2727 (Linking)
VI  - 15
IP  - 2
DP  - 2021 Feb
TI  - 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.
PG  - e0009103
LID - 10.1371/journal.pntd.0009103 [doi]
LID - e0009103
AB  - 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.
FAU - Suemori, Koichiro
AU  - Suemori K
AUID- ORCID: 0000-0002-9154-0162
AD  - Department of Hematology, Clinical Immunology and Infectious Disease, Ehime 
      University Graduate School of Medicine, Toon, Japan.
FAU - Saijo, Masayuki
AU  - Saijo M
AUID- ORCID: 0000-0001-5458-7298
AD  - Department of Virology I, National Institute of Infectious Diseases, Shinjuku, 
      Japan.
FAU - Yamanaka, Atsushi
AU  - Yamanaka A
AUID- ORCID: 0000-0002-4025-8650
AD  - Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, 
      Miyazaki, Japan.
FAU - Himeji, Daisuke
AU  - Himeji D
AD  - Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, 
      Miyazaki, Japan.
FAU - Kawamura, Masafumi
AU  - Kawamura M
AD  - Division of Internal Medicine, Kochi Prefectural Hata Kenmin Hospital, Sukumo, 
      Kochi, Japan.
FAU - Haku, Takashi
AU  - Haku T
AUID- ORCID: 0000-0002-4181-0566
AD  - Department of Respiratory Medicine, Tokushima Prefectural Central Hospital, 
      Tokushima, Japan.
FAU - Hidaka, Michihiro
AU  - Hidaka M
AD  - Department of Hematology, National Hospital Organization Kumamoto Medical Center, 
      Kumamoto, Japan.
FAU - Kamikokuryo, Chinatsu
AU  - Kamikokuryo C
AD  - Department of Emergency and Intensive Care Medicine, Kagoshima University 
      Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
FAU - Kakihana, Yasuyuki
AU  - Kakihana Y
AD  - Department of Emergency and Intensive Care Medicine, Kagoshima University 
      Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima, Japan.
FAU - Azuma, Taichi
AU  - Azuma T
AD  - Department of Hematology, Clinical Immunology and Infectious Disease, Ehime 
      University Graduate School of Medicine, Toon, Japan.
FAU - Takenaka, Katsuto
AU  - Takenaka K
AD  - Department of Hematology, Clinical Immunology and Infectious Disease, Ehime 
      University Graduate School of Medicine, Toon, Japan.
FAU - Takahashi, Toru
AU  - Takahashi T
AUID- ORCID: 0000-0001-5912-0208
AD  - Department of Hematology, Yamaguchi Grand Medical Center, Hofu, Japan.
FAU - Furumoto, Akitsugu
AU  - Furumoto A
AUID- ORCID: 0000-0001-9097-5861
AD  - Division of Infectious Diseases, Department of Internal Medicine, Nagasaki Rosai 
      Hospital, Nagasaki, Japan.
FAU - Ishimaru, Toshiyuki
AU  - Ishimaru T
AUID- ORCID: 0000-0001-9918-5970
AD  - Department of Infectious Diseases, The Japanese Red Cross Fukuoka Hospital, 
      Hakata, Japan.
FAU - Ishida, Masayuki
AU  - Ishida M
AD  - Department of Infectious Diseases, Chikamori Hospital, Kochi, Kochi, Japan.
FAU - Kaneko, Masahiko
AU  - Kaneko M
AUID- ORCID: 0000-0001-6639-3159
AD  - Department of Internal Medicine, Uwajima City Hospital, Uwajima, Japan.
FAU - Kadowaki, Norimitsu
AU  - Kadowaki N
AUID- ORCID: 0000-0002-6473-800X
AD  - Division of Hematology, Kagawa University Hospital, Kida, Japan.
FAU - Ikeda, Kenichi
AU  - Ikeda K
AD  - Department of Internal Medicine, Kagoshima City Hospital, Kagoshima, Japan.
FAU - Sakabe, Shigetoshi
AU  - Sakabe S
AD  - Department of Infectious Diseases, Ise Red Cross Hospital, Ise, Japan.
FAU - Taniguchi, Tomohiro
AU  - Taniguchi T
AUID- ORCID: 0000-0001-6392-3767
AD  - Division of General Internal Medicine & Infectious Diseases, Hiroshima 
      Prefectural Hospital, Hiroshima, Japan.
FAU - Ohge, Hiroki
AU  - Ohge H
AUID- ORCID: 0000-0001-7267-9823
AD  - Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, 
      Japan.
FAU - Kurosu, Takeshi
AU  - Kurosu T
AD  - Department of Virology I, National Institute of Infectious Diseases, Shinjuku, 
      Japan.
FAU - Yoshikawa, Tomoki
AU  - Yoshikawa T
AUID- ORCID: 0000-0001-7601-4036
AD  - Department of Virology I, National Institute of Infectious Diseases, Shinjuku, 
      Japan.
FAU - Shimojima, Masayuki
AU  - Shimojima M
AUID- ORCID: 0000-0002-5745-8413
AD  - Department of Virology I, National Institute of Infectious Diseases, Shinjuku, 
      Japan.
FAU - Yasukawa, Masaki
AU  - Yasukawa M
AUID- ORCID: 0000-0002-1538-433X
AD  - Department of Hematology, Clinical Immunology and Infectious Disease, Ehime 
      University Graduate School of Medicine, Toon, Japan.
LA  - eng
SI  - UMIN-CTR/UMIN000022398
SI  - UMIN-CTR/UMIN000029020
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20210222
PL  - United States
TA  - PLoS Negl Trop Dis
JT  - PLoS neglected tropical diseases
JID - 101291488
RN  - 0 (Amides)
RN  - 0 (Pyrazines)
RN  - 0 (RNA, Viral)
RN  - EW5GL2X7E0 (favipiravir)
RN  - SFTS phlebovirus
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amides/administration & dosage/*adverse effects/blood/*therapeutic use
MH  - Drug-Related Side Effects and Adverse Reactions
MH  - Female
MH  - Humans
MH  - Japan
MH  - Liver Diseases
MH  - Male
MH  - Middle Aged
MH  - Phlebovirus/isolation & purification
MH  - Pyrazines/administration & dosage/*adverse effects/blood/*therapeutic use
MH  - RNA, Viral/isolation & purification
MH  - Severe Fever with Thrombocytopenia Syndrome/*drug therapy/mortality
MH  - Sleep Initiation and Maintenance Disorders/chemically induced
MH  - Treatment Outcome
MH  - Viral Load/drug effects
PMC - PMC7899362
COIS- The authors have declared that no competing interests exist.
EDAT- 2021/02/23 06:00
MHDA- 2021/06/12 06:00
PMCR- 2021/02/22
CRDT- 2021/02/22 17:11
PHST- 2020/10/10 00:00 [received]
PHST- 2020/11/30 00:00 [accepted]
PHST- 2021/02/22 17:11 [entrez]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/06/12 06:00 [medline]
PHST- 2021/02/22 00:00 [pmc-release]
AID - PNTD-D-20-01797 [pii]
AID - 10.1371/journal.pntd.0009103 [doi]
PST - epublish
SO  - PLoS Negl Trop Dis. 2021 Feb 22;15(2):e0009103. doi: 
      10.1371/journal.pntd.0009103. eCollection 2021 Feb.