New Publication: A Randomized Trial of Nafamostat for Covid-19

by ASCOT Trial October 24, 2023

Image: 2020 The University of Tokyo.

We are once again delighted to announce the ASCOT Trial publication in NEJM Evidence, this time for the antiviral domain results. This publication would not be possible without the joint effort of all ASCOT collaborators, investigators, and study participants, and the support from our funders.

The purpose of this domain was to determine whether receipt of a potential antiviral treatment, nafamostat mesylate (nafamostat), showed more benefit compared to not receiving the nafamostat treatment. Nafamostat has been safely used in humans for other conditions, such as pancreatitis, but has not yet been approved for use in COVID-19.

Antiviral treatments may work by blocking the virus from entering human cells, therefore preventing the viruses’ ability to multiply. Laboratory studies have shown that nafamostat may have high antiviral activity, as well as blood thinning properties which may help to treat blood clots found to be associated with COVID-19.

We enrolled 160 participants from Australia, New Zealand and Nepal. Participants who received nafamostat had a 93% probability of better outcomes than those not receiving nafamostat. Specifically, those receiving nafamostat were less likely to require ventilator support for their breathing. However, those who received nafamostat experienced higher rates of hyperkalaemia (elevated potassium levels) and bleeding events compared to those who did not receive the drug.

The trial stopped early, due to declining numbers of patients needing hospital treatment for pneumonia with Covid-19. Due to the trial stopping early, no prespecified stopping criteria were reached; more participants would have provided more data to inform the certainty of the results.

These results are important as the benefit may be sufficient to change practice if nafamostat were low cost, low risk, and easily implemented. But as nafamostat requires a continuous intravenous infusion and has shown increased rates of side effects, in our opinion, a higher probability of effectiveness is needed to recommend its use.

We hope the outcomes from this domain will add to the current pool of evidence and help inform standard practice to treat COVID-19 in non-critically ill patients. The data generated will also be combined with data from other trials to provide a broader picture of the role for nafamostat and related drugs for COVID-19.