Mild lung infection, severe pneumonia, organ failure and death – the SARS-CoV-2 virus’ effect on the human body is wide-ranging and unpredictable. While health professionals follow certain guidelines to treat patients with COVID-19, there is still no evidence-based treatment for the disease. In response to this emergency, many randomised clinical trials testing the effects of different treatments are currently in progress. However, a single trial is usually not a reliable enough assessment. In order for interventions with proven effectiveness to be used in clinical practice, evidence needs to be collected from many trials, and monitored and updated on a continuous basis. With partial support from the EU-funded COMPAR-EU project, researchers are conducting a living systematic review of randomised clinical trials with the aim of aiding evidence-based recommendations for COVID-19 treatment. The first edition of the review, ‘Interventions for treatment of COVID-19: A living systematic review with meta-analyses and trial sequential analyses (The LIVING Project’), has been posted on the ‘ClinOwl’ website.
To effectively assess the beneficial and harmful effects of different COVID-19 treatments, 33 randomised clinical trials with 13 312 participants were included in the study. One trial randomising 6 425 patients showed that an anti-inflammatory drug called dexamethasone could be more beneficial than standard care in 2 cases: all-cause mortality (the death rate from all causes of death in a specific time period), and mechanical ventilation. As reported in the full, open-access review on PLOS Medicine, “482/2,104 died in the dexamethasone group compared with 1,110/4,321 in the standard care group” and “482/2,104 experienced one or more serious adverse events in the dexamethasone group compared with 1,110/4,321 in the standard care group.” A meta-analysis conducted on two trials compared the effect of the broad-spectrum antiviral drug remdesivir with a placebo. Remdesivir appeared to have a more beneficial effect on serious adverse events (medical occurrences that were life-threatening or resulted in hospitalisation or death), but no effect on all-cause mortality or non-serious adverse events. In a meta-analysis of six more trials, hydroxychloroquine, a drug commonly used to prevent and treat malaria, seemed to have a harmful effect on non-serious adverse events and no effect on all-cause mortality or serious adverse events. “Our study showed that dexamethasone and remdesivir might be beneficial for COVID-19 patients, but the certainty of the evidence was low to very low, so more trials are needed. We could reject that hydroxychloroquine is beneficial for COVID-19 in reducing death and serious adverse events at the 20 % relative risk reduction level,” the researchers stated in the review. The results of five single trials were statistically significant but lacked sufficient evidence for any realistic conclusion on drug effects. None of the results in the remaining single trials provided evidence of a difference in the experimental interventions on the researchers’ predefined review outcomes. The conclusion reached was that there is currently no sure evidence-based treatment for COVID-19, a deficiency that could be addressed with more high-quality randomised clinical trials with a low risk of bias. “There is an urgent need for additional evidence, especially trials assessing the effects of dexamethasone and remdesivir,” the authors concluded. Supported by COMPAR-EU (Comparing effectiveness of self-management interventions in 4 high priority chronic diseases in Europe), the review will continue to provide essential data to assist in COVID-19 treatment and clinical research. For more information, please see: COMPAR-EU project website
COMPAR-EU, COVID-19, coronavirus, clinical trials, evidence, review