ABSTRACT
Background: There is currently no validated, effective, safe treatment for severe illness caused by SARS-CoV-2. CVO PLUS CURATIF (CVO+C) is a capsule formulation of two compounds of plant origin with anti-inflammatory and antiviral activities in vitro artemisinin and 1,8-cineole. These compounds have been repurposed for possible use as an oral treatment against COVID-19. Methods: We performed a phase 3 randomized clinical trials on patients over the age of 18 years with SARS-CoV-2 infection confirmed by RT-PCR and mild-to-moderate symptoms. Patients were randomly assigned to receive CVO+C (3 capsules per day) or placebo for 15 days. The primary outcome was the proportion of patients testing negative for SARS-CoV-2 by RT-PCR on day 28 and an absence of severe and serious adverse events. Recovery time, and biological parameters on days 7, 14, 21 and 28 of the trial were considered as secondary outcomes. The safety outcomes considered were adverse events on treatment. Results: In total, 1,576 individuals underwent RT-PCR screening for SARS-CoV-2 infection during the study period. Positive test results were obtained for 591 subjects, 339 of whom met the inclusion criteria for this study. The final analysis included 339 subjects: 132 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. A total of 72 incidences of mild and moderate adverse events, 14 severe adverse events and no serious adverse events were observed in both groups. Conclusion: CVO+C was effective for the treatment of mild-to-moderate COVID-19. None of the patients in the CVO+C arm displayed progression to the severe form of COVID-19. Liver kidney and metabolic functions were preserved in all patients. Trial registration: Registered at Pan African Clinical Trials Registry: (No. PACTR202103601407640, date of approval: 24/03/2021) and approved by the ethics committee of the Ministry of Public Health of Madagascar (approval No. 216 MINSANP/SG/AGMED/CERBM, 17/12/2020)
Subject(s)
COVID-19ABSTRACT
Background: Following the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country. Methods: Nasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases, and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PVR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory confirmed cases were mapped and six genomes of viruses were fully sequenced. Results: Overall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2 positive patients, the median age was 39 years (CI95%: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A, and 20B in favour of several independent introduction of viruses. Conclusions. Our study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.