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Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.
Shinkai, Masaharu; Tsushima, Kenji; Tanaka, Shingo; Hagiwara, Eri; Tarumoto, Norihito; Kawada, Ichiro; Hirai, Yuji; Fujiwara, Sho; Komase, Yuko; Saraya, Takeshi; Koh, Hidefumi; Kagiyama, Naho; Shimada, Megumi; Kanou, Daiki; Antoku, Shinichi; Uchida, Yujiro; Tokue, Yutaka; Takamori, Mikio; Gon, Yasuhiro; Ie, Kenya; Yamazaki, Yoshitaka; Harada, Kazumasa; Miyao, Naoki; Naka, Takashi; Iwata, Mitsunaga; Nakagawa, Atsushi; Hiyama, Kazutoshi; Ogawa, Yoshihiko; Shinoda, Masahiro; Ota, Shinichiro; Hirouchi, Takatomo; Terada, Jiro; Kawano, Shuichi; Ogura, Takashi; Sakurai, Tsutomu; Matsumoto, Yoshihiko; Kunishima, Hiroyuki; Kobayashi, Osamu; Iwata, Satoshi.
  • Shinkai M; Department of Respiratory Medicine, Tokyo Shinagawa Hospital, 6-3-22 Higashioi, Shinagawa-ku, Tokyo, 140-8522, Japan.
  • Tsushima K; Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare, 852 Hatakeda, Narita, Chiba, 286-8520, Japan.
  • Tanaka S; Department of Otolaryngology, Self-Defense Forces Central Hospital, 1-2-24 Ikejiri, Setagaya-ku, Tokyo, 154-8532, Japan.
  • Hagiwara E; Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomiokahigashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan.
  • Tarumoto N; Department of Infectious Disease and Infection control, Saitama Medical University Hospital, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama, 350-0495, Japan.
  • Kawada I; Division of Pulmonary Medicine, Department of Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
  • Hirai Y; Department of Infectious Diseases, Tokyo Medical University Hachioji Medical Center, 1163 Tatemachi, Hachioji, Tokyo, 193-0998, Japan.
  • Fujiwara S; Department of Infectious Diseases, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan.
  • Komase Y; Department of Respiratory Internal Medicine, St. Marianna University Yokohama City Seibu Hospital, 1197-1 Yasashi-cho, Asahi-ku, Yokohama, Kanagawa, 241-0811, Japan.
  • Saraya T; Department of Respiratory Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
  • Koh H; Division of Pulmonary Medicine, Department of Internal Medicine, Tachikawa Hospital, 4-2-22 Nishiki-cho, Tachikawa, Tokyo, 190-8531, Japan.
  • Kagiyama N; Department of Respiratory Medicine, Saitama Cardiovascular and Respiratory Center, 1696 Itai, Kumagaya, Saitama, 360-0197, Japan.
  • Shimada M; Department of General Internal Medicine, Tokai University Oiso Hospital, 21-1 Gakkyo, Oiso-machi, Naka-gun, Kanagawa, 259-0198, Japan.
  • Kanou D; Department of Respiratory Internal Medicine, Yokohama Rosai Hospital, 3211 Kozukue-cho, Kohoku-ku, Yokohama, Kanagawa, 222-0036, Japan.
  • Antoku S; Department of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital, 2-24-18 Higashikoiwa, Edogawa-ku, Tokyo, 133-0052, Japan.
  • Uchida Y; Department of General Medicine, Kitakyushu Municipal Medical Center, 2-1-1 Bashaku, Kokurakita-ku, Kitakyushu, Fukuoka, 802-8561, Japan.
  • Tokue Y; Infection Control and Prevention Center, Gunma University Hospital, 3-39-15 Showamachi, Maebashi, Gunma, 371-8511, Japan.
  • Takamori M; Department of Respiratory Medicine, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo, 183-8524, Japan.
  • Gon Y; Department of Respiratory Medicine, Nihon University Itabashi Hospital, 30-1 Oyaguchikami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.
  • Ie K; Department of General Internal Medicine, Kawasaki Municipal Tama Hospital, 1-30-37 Shukugawara, Tama-ku, Kawasaki, Kanagawa, 214-8525, Japan.
  • Yamazaki Y; Department of Respiratory and Infectious Diseases, Nagano Prefectural Shinshu Medical Center, 1332 Suzaka, Suzaka, Nagano, 382-8577, Japan.
  • Harada K; Department of Cardiology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
  • Miyao N; Department of Internal Medicine, Nippon Koukan Hospital, 1-2-1 Kokandori, Kawasaki-ku, Kawasaki, Kanagawa, 210-0852, Japan.
  • Naka T; Department of Neurology, Higashiosaka City Medical Center, 3-4-5 Nishiiwata, Higashiosaka, Osaka, 578-8588, Japan.
  • Iwata M; Department of Emergency and General Internal Medicine, Fujita Health University Hospital, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi, 470-1192, Japan.
  • Nakagawa A; Department of Respiratory Medicine, Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.
  • Hiyama K; Department of Infectious Diseases, National Hospital Organization Fukuokahigashi Medical Center, 1-1-1 Chidori, Koga, Fukuoka, 811-3195, Japan.
  • Ogawa Y; Department of Infectious Diseases, Sakai City Medical Center, 1-1-1 Ebarajicho, Nishi-ku, Sakai, Osaka, 593-8304, Japan.
  • Shinoda M; Department of Respiratory Medicine, Tokyo Shinagawa Hospital, 6-3-22 Higashioi, Shinagawa-ku, Tokyo, 140-8522, Japan.
  • Ota S; Department of Respiratory Medicine, Tokyo Shinagawa Hospital, 6-3-22 Higashioi, Shinagawa-ku, Tokyo, 140-8522, Japan.
  • Hirouchi T; Department of Respiratory Medicine, Tokyo Shinagawa Hospital, 6-3-22 Higashioi, Shinagawa-ku, Tokyo, 140-8522, Japan.
  • Terada J; Department of Pulmonary Medicine, School of Medicine, International University of Health and Welfare, 852 Hatakeda, Narita, Chiba, 286-8520, Japan.
  • Kawano S; Department of Internal Medicine, Self-Defense Forces Central Hospital, 1-2-24 Ikejiri, Setagaya-ku, Tokyo, 154-8532, Japan.
  • Ogura T; Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, 6-16-1 Tomiokahigashi, Kanazawa-ku, Yokohama, Kanagawa, 236-0051, Japan.
  • Sakurai T; Scientific Information Department, FujiFilm Toyama Chemical Co., Ltd., 3-4-8 Hatchobori, Chuo-ku, Tokyo, 104-0032, Japan.
  • Matsumoto Y; Scientific Information Department, FujiFilm Toyama Chemical Co., Ltd., 3-4-8 Hatchobori, Chuo-ku, Tokyo, 104-0032, Japan.
  • Kunishima H; Department of Infectious Diseases, School of Medicine, St. Marianna University, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
  • Kobayashi O; Department of Infectious Diseases, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
  • Iwata S; Department of Infectious Diseases, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. siwata@ncc.go.jp.
Infect Dis Ther ; 10(4): 2489-2509, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1375855
ABSTRACT

INTRODUCTION:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy.

METHODS:

COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 12. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions.

RESULTS:

A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher.

CONCLUSIONS:

The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. TRIAL REGISTRATION Clinicaltrials.jp number JapicCTI-205238.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Type of study: Controlled clinical trial / Risk factors Language: English Journal: Infect Dis Ther Clinical aspect: Etiology Year: 2021

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Full text: Available Collection: International databases Database: MEDLINE Document Type: Article Type of study: Controlled clinical trial / Risk factors Language: English Journal: Infect Dis Ther Clinical aspect: Etiology Year: 2021
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