Discussion
inflammation, infection
INFLAMMATION, DISEASE, INFECTION
We performed an open-label, multi-center, randomized clinical trial to explore whether teprenone induced HSPs that prevented worsening of COVID-19. Unfortunately, teprenone was not effective.In a retrospective analysis, the survival rate was significantly higher in severe COVID-19 patients who received, as compared to those who did not receive, Jusvinza, a derivative of HSP60, (90.4 vs. 39.5%, p < 0.0001). Also, inflammation and coagulation biomarkers were significantly reduced in the Jusyinza group [In this study, the patients in the teprenone group were registered later (time from disease onset to randomization 7 vs. 5 days), which implies less severe infection since they did not need intubation until at least 7 days after onset, However, despite such a potentially favorable factor, teprenone did not show a benefit in this study.There are several potential reasons why teprenone lacked clinical activity. First, the intubation rate (the primary endpoint) was lower than expected. Based on initial cohort data, we had assumed that the rate would be 22% in the no-teprenone group, whereas the actual rate was 2% (Our study had certain limitations. First, this was an open-label non-blinded study; bias was possible. This study started in the early stages of the COVID-19 pandemic when many facilities were not accustomed to handling COVID-19 inpatients. We considered that blinding and a placebo would complicate the study and increase the risk of infection for medical staff. Therefore, blinding was not implemented in this study. Second, this was a phase 2 study with a small number of patients, so the results are not definitive. The study has a low power of 64% at a one-sided 0.1% significance level. This is because this study was conducted in the early stages of the COVID-19 pandemic when it was difficult to estimate the number of COVID-19 cases; we thought that the setting would be achievable or realistic. Third, the decision to intubate is subjective and may have been affected by factors other than disease severity. Furthermore, the intubation rate was lower than estimated, limiting the generalizability of the results. Therefore, the findings should be interpreted with caution. Finally, this study was conducted entirely in Japan, so the generalizability of our results to other countries remains unclear.