Hochuekkito (Bu-Zhong-Yi-Qi-Tang) for general fatigue in long COVID: protocol for a multicentre randomised double-blind placebo-controlled trial

Abstract Background General fatigue in patients with long COVID is a major medical issue in primary care. Since there is a lack of evidence-based treatments, Japanese traditional (Kampo) medicine has gained attention in Japan. However, there has been no study to evaluate the efficacy of Japanese traditional medicine. This study aimed to evaluate the efficacy of hochuekkito (Bu-Zhong-Yi-Qi-Tang) in long COVID patients with general fatigue. Methods/design The primary objective of this study is to assess whether the Japanese traditional (Kampo) formulation, hochuekkito, effectively alleviates general fatigue associated with long COVID. Designed as a randomised, double-blind, placebo-controlled trial, the study involves participants who, after providing written informed consent, are allocated to one of two treatment arms: arm A (hochuekkito) or arm B (placebo). The intervention will last for 6 weeks, during which treatment assignment remains concealed from both study personnel and participants. The primary measure of efficacy is the score on the Japanese version of the Fatigue Assessment Scale (FAS) evaluated at the 6-week post-intervention mark. The target sample size is 156 participants, divided equally into two arms of 78 patients each. Recruitment commenced in December 2024 and is expected to conclude by December 2026. Discussion General fatigue is the most frequent symptom of long COVID and is often treated by primary care physicians. Long COVID limits the social life of those afflicted. The goal of this project is to demonstrate a treatment for long COVID general fatigue with a high level of evidence. Trial registration Japan Registry of Clinical Trials (jRCT), trial registration: jRCTs061240010 ( https://jrct.mhlw.go.jp/latest-detail/jRCTs061240010 ), registered on 15th May 2024.