The PLATCOV trial has been running continuously since September 2021. Thanks to the tireless efforts of the study nurses and doctors, over 1700 patients presenting with COVID19 infections have now been randomised, 90% of whom were recruited in the Hospital for Tropical Diseases in Bangkok. This pharmacometric platform trial has characterised the antiviral efficacy for many potential interventions: ivermectin, favipiravir, fluoxetine, remdesivir, molnupiravir, ritonavir-boosted nirmatrelvir, and casirivimab/imdevimab, with results for ensitrelvir and tixagevimab/cilgavimab coming soon. The trial data has also provided important insights into how the SARS-CoV-2 infection has changed over time.
Work by Dr Phrutsamon Wongnak (Chang) published in the Lancet Infectious Diseases has shown that rates of oropharyngeal viral clearance have accelerated dramatically since the trial started. In September 2021, untreated patients had a viral clearance half-life of around 16 hours. By October 2023, this half-life had reduced to around 9 hours. The exact causes of this increase in viral clearance are difficult to pinpoint, but are likely to be due to a complex interplay between host immunity and viral evolution. But these temporal changes have practical consequences, notably regarding the design and interpretation of antiviral drug studies. The results highlight an important aspect of platform trials: comparison with contemporaneous controls is essential to avoid temporal confounding. An ineffective intervention might appear effective if compared with historical controls.
The editorial in the Lancet ID emphasises the importance of these pharmacometric platform trials, especially in the context of pandemic preparedness: “The PLATCOV study design could act as a model not only for SARS-CoV-2 but also for other emerging respiratory virus infections. [..]. The challenge will be to run these studies in the frenzy of an unfolding pandemic with overwhelmed health services and shortages of everything. It is imperative to have such a study framework ready for the next pandemic to avoid the errors that were made with COVID-19.”
In parallel to PLATCOV, the AD ASTRA trial is comparing antiviral efficacies of the main influenza drugs. Influenza is likely to be the next pandemic. We hope this trial will allow for rational selection of the best drugs to treat seasonal and possibly pandemic influenza.
Temporal changes in SARS-CoV-2 clearance kinetics and the optimal design of antiviral pharmacodynamic studies: an individual patient data meta-analysis of a randomised, controlled, adaptive platform study (PLATCOV). Wongnak P et al, Lancet Infect Dis. 2024 Apr.
- With thanks to Phrutsamon Wongnak for text.