Outcomes of phase 3 clinical trial of CVO PLUS CURATIF capsules for COVID-19 treatment

By Dr. Sanchari Sinha Dutta, Ph.D.Feb 23 2022Reviewed by Aimee Molineux

A phase 3 randomized clinical trial has recently been conducted to investigate the efficacy of a capsule formulation (CVO PLUS CURATIF) in treating mild-to-moderate coronavirus disease 2019 (COVID-19) patients. The CVO PLUS CURATIF capsules contain two plant-derived anti-inflammatory and anti-viral compounds, namely artemisinin and 1,8-cineole.

*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

The detailed report of the trial is currently available on the Research Square* preprint server while under consideration in the journal BMC Infectious Diseases.    

Background

With the progression of the COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many vaccines have been developed and marketed in record speed and time. In both clinical trials and real-world studies, most of these vaccines have shown high efficacy in preventing SARS-CoV-2 infection and reducing disease severity, hospitalization, and mortality.

Regarding therapeutic interventions, several clinically-approved anti-viral medicines have been repurposed to treat moderate-to-severe COVID-19 patients, especially hospitalized patients. Some of these medicines have shown acceptable efficacy in reducing viral load and symptom intensity and shortening recovery time. However, it is still controversial whether these medicines have the potential to reduce disease progression and mortality.

In the current phase 3 clinical trial, the scientists have investigated anti-SARS-CoV-2 efficacy of a capsule formulation CVO PLUS CURATIF, which contains two plant-derived compounds, namely artemisinin and 1,8-cineole.

Artemisinin, derived from a Chinese medicinal plant, is primarily used in the preparation of antimalarial medicines. The compound is known to interact with the binding hotspots of the SARS-CoV-2 spike protein to exert antiviral effects.

The other compound 1,8-cineole is found in large quantities in many essential oils extracted from plants. Studies have shown that 1,8-cineole inhibits SARS-CoV-2 main protease, and thus, prevents viral replication.

The capsule formulation CVO PLUS CURATIF is composed of Artemisia annua L. extract and an essential oil from leaves of Cinnamomum camphora L. The essential oil and the Artemisia annua L. extract are rich sources of 1,8-cineole and artemisinin, respectively.

Study design

A total of 339 individuals with laboratory-confirmed SARS-CoV-2 infection participated in the clinical trial. The participants were randomly assigned to two groups: a treatment group and a placebo (control) group. The treatment group participants (n=132) were orally administered with three CVO PLUS CURATIF capsules per day for 15 days. In the control group (n=144), the participants were administered with a placebo formulation using the same regimen.

All participants were followed-up on days seven, 14, 21, and 28 to assess treatment efficacy and safety profiles. The viral load and treatment-induced adversities were recorded at each visit. In addition, routine clinical, hematological, and biochemical parameters were done.

Treatment efficacy

A significantly higher treatment efficacy was observed in participants who received CVO PLUS CURATIF capsules compared to that in placebo-treated participants. The virological treatment failure (insufficient viral load reduction) was observed in 11 and 28 participants from the treatment and control groups, respectively. In addition, clinical treatment failure (new or recurrent clinical events) was observed in six and eight participants from the treatment and control groups, respectively. No biological treatment failure was reported.   

Regarding viral clearance, about 42%, 70%, 76%, and 89% of treatment group participants had undetectable viral RNA on days seven, 14, 21, and 28, respectively. In contrast, viral RNA levels were undetectable in about 27%, 41%, 57%, and 78% of control group participants on days seven, 14, 21, and 28 days, respectively.

A relatively faster recovery was observed in participants treated with CVO PLUS CURATIF capsules. The average recovery time in the treatment and control groups was 14 days and 21 days, respectively.

Safety profile

Overall, about 72 incidences of mild-to-moderate adversity and 14 incidences of severe adversity were observed during the study period. The frequency of adverse events was higher in placebo-treated participants compared to that in CVO PLUS CURATIF capsule-treated participants.

The most reported mild-to-moderate adversity was digestive problems, which occurred more frequently in placebo-treated participants. In addition, somatic, pulmonary, neurological, muscular, and cutaneous adversities were observed among participants.

Two participants from the treatment group and three participants from the placebo group showed severe asthenia and cardiac disturbance, respectively. Dyspnea was observed in two participants from each group. In addition, severe digestive adversities were observed in two of the treatment group participants and one placebo group participant. The appearance of severe adversities led to the early termination of the treatment.

The progression of COVID-19 to a severe form was not observed in any participants from the treatment group. However, two placebo-treated participants developed severe COVID-19 during the study period.

Study significance

The study findings indicate that CVO PLUS CURATIF capsules are effective in accelerating viral clearance, reducing recovery time, and preventing COVID-19 progression. In addition, the treatment regimen has shown an acceptable safety profile.  

*Important notice: Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.