Favipiravir, camostat, and ciclesonide combination therapy in patients with moderate COVID-19 pneumonia with/without oxygen therapy: An open-label, single-center phase 3 randomized clinical trial

EClinicalMedicine

Takuya Kawahara¹  Retsu Fujita²  Yuji Tada²  Taku Kinoshita³  Kenji Tsushima⁴  Toru Kinouchi⁴  Yuri Isaka⁴  Hiroshi Tajima⁴  Jiro Terada⁴  Yuichiro Takeshita⁴  Yasutaka Hirasawa⁵ 

[1] Correspondence: 852 Hatakeda, Narita city, 286-8520, Chiba, Japan, Telephone: [phone], Fax: [phone].;Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan;Clinical Research Promotion Center, The University of Tokyo Hospital, Tokyo, Japan;Department of Pulmonary Medicine, International University of Health and Welfare Narita Hospital, Chiba, Japan;Innovation and Research Support Center, Graduate School of Medicine, International University of Health and Welfare, Tokyo, Japan;

关键词: COVID-19;    Camostat;    Ciclesonide;    Combination therapy;    Favipiravir;    Hospital stay;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary:Background: The effectiveness of combination therapy for COVID-19 pneumonia remains unclear. We evaluated favipiravir, camostat, and ciclesonide combination therapy in patients with moderate COVID-19 pneumonia. Methods: In this open-label phase 3 study, hospitalized adults who were positive for SARS-CoV-2 and had COVID-19 pneumonia were enrolled prior to official vaccination drive in Japan. Participants were randomly assigned to favipiravir monotherapy or favipiravir + camostat + ciclesonide combination therapy. The primary outcome was the length of hospitalization due to COVID-19 infection after study treatment. The hospitalization period was calculated from the time of admission to the time of patient discharge using the clinical management guide of COVID-19 for front-line healthcare workers developed by the Japanese Ministry of Health, Labour, and Welfare (Version 3). Cases were registered between November 11, 2020, and May 31, 2021. Japan Registry of Clinical Trials registration: jRCTs031200196. Findings: Of 121 enrolled patients, 56 received monotherapy and 61 received combination therapy. Baseline characteristics were balanced between the groups. The median time of hospitalization was 10 days for the combination and 11 days for the monotherapy group. The median time to discharge was statistically significantly lower in the combination therapy vs monotherapy group (HR, 1·67 (95% CI 1·03–2·7; P = 0·035). The hospital discharge rate was statistically significantly higher in the combination therapy vs monotherapy group in patients with less severe COVID-19 infections and those who were ≤60 years. There were no significant differences in clinical findings between the groups at 4, 8, 11, 15, and 29 days. Adverse events were comparable between the groups. There were two deaths, with one in each group. Interpretation: Combination oral favipiravir, camostat and, ciclesonide therapy could decrease the length of hospitalization stays without safety concerns in patients with moderate COVID-19 pneumonia. However, lack of hard clinical primary outcome is one of the major limitations of the study. Funding: This research was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 20fk0108261h0001.

【 授权许可】

Unknown