Getting STOIC on COVID

What if there was a miracle treatment for early COVID? It reduces your risk of hospitalization by 90% and helps prevent long covid. What if we in general practice could readily prescribe this treatment for our patients? What if we already prescribe it every day?

Early in the pandemic, it became clear that while patients with co-morbidity fared poorly, surprisingly those with chronic respiratory disease were significantly under-represented. This led to the hypothesis that inhaled corticosteroids could be the missing link.

And so the STOIC trial was borne – a primary care-based pragmatic randomized trial conducted in the UK, funded by the Oxfordshire NIHR Biomedical Research Centre and AstraZeneca, with the aim to test if ICS would modify the course of early covid in non-hospitalised patients.

It recruited 146 new COVID cases within 7 days of symptom onset, with no oral or inhaled steroid use in the previous 7 days, randomized in a 1:1 ratio to either inhaled budesonide dry powder inhaler 800mcg twice daily used until symptom resolution (up to 28 days), or usual care. The primary endpoint of the study was COVID-19-related urgent care visit, emergency department assessment, or hospitalisation.

The results have now published in pre-print. This of course means the data still needs to undergo rigorous peer review before formal publication but the results, if they stand that scrutiny, are compelling:

·      Only 1 person in the budesonide group vs. 10 in the usual care group required urgent or hospital care – a statistically significant difference (P=0.004)

o  Numbers needed to treat = 8

·      Time to clinical recovery was also shorter – 8 v 7 days, with less fever overall as well

·      Fewer patients had ongoing symptoms at 14 days with budesonide (18%) vs usual care (28%)

This data suggests that inhaled corticosteroids modify the disease process, substantially reducing the risk of hospitalization by a similar degree to vaccination (no one is advocating it instead of vaccination), and that through this moderation long covid may be less likely.

It really does appear to be a ‘miracle treatment’. The pre-print published 7 weeks ago, why no media frenzy? Firstly we need to consider the limitations of the STOIC trial.

Initially, the aim was to recruit close to 200 participants which ultimately proved impossible as the 2^nd covid wave waned. The trial investigators took the difficult decision to close the trial early, something that often rings alarm bells, but they did seek independent statistical assessment to ensure this was appropriate and the conclusion was increasing the trial population to the pre-specified level was unlikely to change the outcome.

The study was not placebo-controlled. This would have been ideal but hard to achieve in the time scales we’ve all been working on. Comparison against usual care is still very helpful as this is what we’ve all been doing for 12 months, plus it seems unlikely such a substantial effect could be purely driven by the placebo effect.

It may be nothing relating to the trial itself. After the initial frenzy when any pre-print paper on covid could make headline news that some order it may be this is a welcome return to the usual scientific process. It may be the perpetual media bias against general practice which still fails to get the recognition it deserves for the treatments it can offer compared to the latest unaffordable hospital drug with a tiny percentage improvement in some (often rare) outcome. It may be that AstraZeneca is currently in the doghouse with the international political community, much to the bemusement of millions of Britons who have been gladly vaccinated and despite having rapidly produced an effective, lifesaving vaccine on a non-profit basis for worldwide use (it’s not often we defend big pharma…). It may be the media was simply too busy talking about covid waves, death rates, vaccination woes, and Brexit.

Perhaps it’s because when something is too good to be true, that’s often the case. Clinicians have been burned many times before. No one believes in miracles. A healthy dose of scepticism is warranted. But the study appears a good study and the data compelling.

So should we start prescribing inhaled steroids for early covid in the community? Personally, I will wait until the paper is formally published and peer-reviewed, reportedly in the very near future. Further studies in the UK and globally are also investigating inhaled steroids in covid and should also publish soon. In the meantime let’s keep doing the good work we’ve been doing for the past year but also take heart that the future for our patients in the time of covid looks very promising.