Parenteral remdesivir accelerates viral clearance among patients with early symptomatic COVID-19 infection, according to a study in the Journal of Infectious Diseases.
Lingering uncertainty regarding the effectiveness of varying COVID-19 therapies has resulted in major worldwide differences in practice guidelines. Study authors therefore reported on findings involving remdesivir antiviral activity from the PLATCOV trial (ClinicalTrials.gov Identifier: NCT05041907), an ongoing phase 2 open-label randomized controlled pharmacometric platform trial.
Adults aged 18 to 50 years (mean age, 30.1 years) with early symptomatic COVID-19 (symptoms for <4 days) who had been previously healthy were included in the study; all had an oxygen saturation of at least 96% and were unimpeded in their activities of daily living. The primary outcome measure was the rate of viral clearance among patients using remdesivir.
The modified intention-to-treat population included 131 patients, 67 receiving remdesivir and 64 randomly assigned to receive ivermectin, casirivimab/imdevimab, favipiravir, nitazoxanide, fluoxetine, molnupiravir, or nirmatrelvir/ritonavir. Remdesivir was administered in an intravenous infusion for 60 minutes in an initial adult dose of 200 mg, followed by 100 mg once daily for 4 days. All participants received standard symptomatic treatment.
The simple pharmacometric methodology presented demonstrates the in vivo antiviral efficacy of remdesivir and is readily performed anywhere where accurate qPCR viral quantitation can be performed.
Each participant had a median of 18 sample swabs taken to measure viral density in the first 8 days, resulting in a total of 2356 quantitative polymerase chain reaction (qPCR) analyses; 86% of these swabs were above the lower limit of detection.
Clearance of oropharyngeal virus in patients randomized to remdesivir was 42% faster compared with the control arm (95% CI, 18%-73%; probability of >12.5% acceleration: 0.99). The median estimate of viral clearance half-lives under the linear model was 12.8 (range, 4.8-50.0) hours for the remdesivir group and 18.0 (range, 3.6-46.7) hours for the control group.
Oropharyngeal swabbing and treatments were well-tolerated. In the control arm, 3 serious adverse events (AEs) occurred vs 1 in the remdesivir arm. In addition, 2 patients in the control group and 1 in the remdesivir group had asymptomatic increased creatinine phosphokinase level (>10 times ULN) owing to COVID-19-related skeletal muscle damage. No treatment-related serious AEs occurred.
Among several limitations, the researchers intentionally assessed the COVID-19 antiviral interventions in low-risk adults with high viral burdens in order to optimize the comparative assessment of the different drugs, thus excluding elderly and other individuals with a higher risk for disease progression. Other limitations include the open-label design and a lack of statistical significance in the time to symptom resolution and time to fever clearance.
“Remdesivir continues to have a role in the treatment of COVID-19 for certain populations,” stated the investigators. “The simple pharmacometric methodology presented demonstrates the in vivo antiviral efficacy of remdesivir and is readily performed anywhere where accurate qPCR viral quantitation can be performed.”