A structured summary of a study protocol for a multi-center, randomized controlled trial

• Published in: Trials 2021-01, Vol.22 (1)
• Main Authors: Namiki, Takao, Takayama, Shin, Arita, Ryutaro, Ishii, Tadashi, Kainuma, Mosaburo, Makino, Toshiaki, Mimura, Masaru, Yoshino, Tetsuhiro, Nogami, Tatsuya, Arai, Makoto, Sato, Juichi, Tanaka, Koichiro, Nakae, Hajime, Igari, Hidetoshi, Ozawa, Yoshihito, Shiko, Yuki, Kawasaki, Yohei, Nezu, Masahiko, Ito, Takashi
• Format: Article
• Language: English
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-020-04939-2

Objective We aimed to test our hypothesis that traditional Japanese (Kampo) medicine, hochuekkito (Hochu-ekki-to: HET) has a preventive effect for the symptoms on COVID-19. Trial design The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator sponsored, two-arm study. Participants Six thousand participants will be recruited from healthy hospital workers in 7 Japanese University Hospitals. Inclusion criteria: 1. Age from 20 to 75 years old at the time of registration 2. Asymptomatic and body temperature below 37[degrees]C at the time of registration 3. Capable of eating orally Exclusion criteria: 1. Previous upper respiratory inflammation due to viral infection (including suspected COVID-19) 2. Taking immunosuppressants 3. Allergic to the Kampo medicines used in this study 4. History of hypokalaemia, severe hypertension, severe liver dysfunction, and interstitial pneumonia 5. Regularly taking other Kampo medicines 6. Pregnant or possibly pregnant 7. Participating in other research 8. Judged to be unsuitable for this study by the doctor in charge Intervention and comparator Kampo group: participants receive HET in 9 tablets 2 times per day for 8 weeks. Control group: participants receive placebo in the same dosage as the Intervention group - 9 tablets 2 times per day for 8 weeks. Placebo tablets are identical in appearance and package to HET. Taste of placebo is different from that of HET. The Ohsugi Pharmaceutical Co. Ltd, Osaka, Japan manufactured the placebo and HET. Main outcomes Primary outcome: Number of patients with a SARS-CoV-2 RNA by ploymerase chain reaction (PCR) positive result with at least one symptom (fever, cough, sputum, malaise, shortness of breath) during the 12-week study period (including the 4-week observation period after oral administration). Secondary outcomes: 1. Period from infection to onset 2. Period from the appearance of symptoms to the disappearance of PCR positive 3. Number of days until the appearance or improvement of symptoms 4. Severe stage: presence of hospitalization 5. Shock stage: ICU management required for mechanical ventilation, shock vitals or failure of organ(s) other than lungs Safety endpoints include numbness in the hands and/or feet, edema, skin rash or other allergic symptoms, and gastric discomfort. Randomisation Patients are randomized (1:1 ratio) to each group using minimization implemented with the Electric data capture system (DATATRAK Enterprise Clo