Efficacy and Safety of CVO PLUS CURATIF Capsules, Malagasy Improved Traditional Medication for Treating COVID-19: A Randomized, Double- Blind, Placebo-Controlled Trial

Author(s): Rianasoambolanoro Rakotosaona, Sedera A. Mioramalala, Malala Arinomenjanahary Rakotoarisoa, Antsa Rakotondrandriana, Emmanuel Randrianarivo, Felana Rabetokotany, Fanomezantsoa Rakoto, Dominique Razafimandimby, Arsène Ravelo, Fridolin Maminiaina, Rabenja Rapelanoro, Zely Randriamanantany, Rivo Andry Rakotoarivelo, Olivat Rakoto Alson, Claude Arsène Ratsimbasoa

Background: Only a few drugs are currently approved to treat COVID-19. CVO PLUS CURATIF (CVO+C) is a capsule formulation of artemisinin and 1,8-cineole, two plant-derived compounds with anti-inflammatory and antiviral properties in vitro. These compounds have been repurposed for potential use as an oral COVID-19 treatment.

Methods: We performed a phase 3 randomized clinical trial on patients over the age of 18 years with SARS-CoV-2 infection and mild-tomoderate symptoms. Patients were randomly assigned to receive CVO+C (3 capsules per day) or placebo. The primary outcomes were the proportion of patients testing negative for SARS-CoV-2 on day 28 and the absence of serious adverse events. Secondary outcomes included recovery time and biological markers.

Results: In total, 1,576 individuals were screened, 339 of whom met the inclusion criteria. After data cleaning, 132 were from the CVO+C arm and 144 from the placebo arm. Treatment efficacy differed significantly (p = 0.011) between the CVO+C arm (87.1%, 95% CI: 81.3%-92.9%, with 70.45% of patients cured by day 14) and the placebo arm (75.0%, 95% CI: 67.8%-82.1%), with an OR of 2.25. The median time to recovery was 14 days for the CVO+C group and 21 days for the placebo group. There were 72 mild and moderate adverse events, 14 severe adverse events, and no serious adverse events in either group.

Conclusions: CVO+C was effective for the treatment of mild-to-moderate COVID-19. None of the patients in the CVO+C arm developed the severe form of COVID-19. Patients’ liver, kidney, and metabolic functions were preserved.