Efficacy of Andrographis paniculata extract treatment in mild to moderate COVID-19 patients being treated with favipiravir: A double-blind, randomized, placebo-controlled study (APFaVi trial)
Taweegrit Siripongboonsitti, Teerapat Ungtrakul, Kriangkrai Tawinprai, Chirayu Auewarakul, Wipada Chartisathian, Thitikan Jansala, Rattana Julsawad, Kamonwan Soonklang, Nithi Mahanonda, Chulabhorn Mahidol
Phytomedicine, doi:10.1016/j.phymed.2023.155018
Background: While favipiravir had been the standard anti-SARS-CoV-3 drug for COVID-19 treatment in Thailand, the efficacy of favipiravir treatment is controversial. Andrographis paniculata extract (APE) inhibits viral entry, exhibits immunomodulatory effects, and proposes to have the potential for early-stage COVID-19 treatment. Methods: A randomized, double-blind, placebo-controlled trial was performed in Thailand during June -September 2021. Non-severe COVID-19 patients were randomized 1:1 to groups receiving 180 mg/day of APE plus favipiravir (APE-FPV group) or placebo plus favipiravir (placebo-FPV group). Efficacy in preventing disease progression to severe COVID-19 was assessed on day 4, using World Health Organization Clinical Progression Scale (WHO-CPS) score and visual analog scale (VAS) for acute respiratory tract infection symptoms. Results: Of 146 patients, there were 73 patients in each group. Non-deterioration of WHO -CPS scores on day 4 was 98.63% versus 97.26% of patients in the APE-FPV and placebo-FPV groups (p = 1.000). No difference in supplemental oxygen, hospitalization, and death was shown in both groups. The oxygen supplemental was 4.11% in the placebo-FPV group. The interleukin (IL)-1β was significantly lower in the APE than in the placebo-FPV group throughout the study. We found no difference in virologic outcomes between groups and no substantial adverse events. Conclusions: APE treatment did not demonstrate additional clinical and virological benefits in patients with mild to moderate COVID-19 being treated with favipiravir. Early reduction of IL-1β with APE may be advantageous in preventing cytokine storms in severe COVID-19 and requires further study.
Authors' contributions T.S. and N.M. had full access to all the data in this study and took responsibility for data integrity and accuracy. C.M., N.M., C.A., K.T., T. S., T.U., W.C., T.J., R.J., and K.S. contributed equally to the study.
Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Taweegrit Siripongboonsitti reports financial support, administrative support, article publishing charges, equipment, drugs, or supplies, and statistical analysis were provided by Chulabhorn Royal Academy.
Supplementary materials Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.phymed.2023.155018.
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