February 10, 2021

expert reaction to preprint on an RCT of inhaled budesonide in the treatment of early COVID-19

A preprint, an unpublished non-peer reviewed study, looks at a  randomised control trial (RCT) of inhaled budesonide in the treatment of early COVID-19 illness.

Prof Tim Higenbottam, President, Faculty of Pharmaceutical Medicine, said:

“A much-anticipated study – wonderful to see a study in the community and in a simple well recognised therapy already in use in millions of asthmatic patients that starts treatment on average within 3 days of first symptom onset.

“This is a quality designed study, with an independent Data Safety Management Committee and an a priori early stopping criteria – initial power calculation based on limited expected outcome that proved to be an over-estimate of the needed number of randomised patients.

“There is very high qPCR confirmed diagnosis. However, the study is open without double-blind which could include bias in patient selection by using an age range that is younger and with limited co morbidities associated with increased risk of hospitalisation and death. However, it establishes a good principle, recovery being fast and limited adverse effects. Also the treatment could be economic and used worldwide – roll on a bigger study and broader age range and in populations with risk factors of severe COVID-19 pneumonia.

“The analysis is very clear and follows the methods that have emerged as standard in intervention studies in COVID-19.

“Next step, a randomised and double-blind clinical study should be undertaken to confirm the findings and particularly including older age adults with more significant comorbidities, with the aim of starting treatment within 4 days of first symptom onset.

Is the trial large enough to be confident in the results?

“Yes, as a proof of concept – to be followed by a large-scale study double blind and in many geographies as this is a product that could have a major global impact.

Are there any limitations or caveats you’d like journalist to be aware of in this trial?

“The measurements and the primary outcome measurements look most effective to demonstrate early recovery – simply showing not requirement for secondary medical care (with defined activities). Concerns are the lack of double blinding the therapy which could involve bias, the inclusion of young adults at low risk of complicated disease and the limited number of individuals with comorbid conditions increasing risk of disease.

Which patients is this trial targeting – at which stage in illness would it be given?

“This study focused on early onset of COVID-19 symptoms of patients in the community.

“Next step, the large-scale studies needs to include both patients diagnosed on symptoms and those confirmed on qPCR testing, and increased proportion of older individuals with comorbidities increasing risk of hospitalisation and death from COVID.

What is the likely mechanism by which this drug may work in treating COVID-19?

“There are two plausible mechanisms. The first being the recognised effect of inhaled steroids (often with increased doses) can prevent the development of severe exacerbations on Asthma by limiting the viral induced inflammatory responses. The second is the human data and in vitro data the ACE-2 receptors are inhibited by topical steroids.

What are the next stages in deciding whether this should become part of treating COVID?

“Next step is to consider large scaled randomised double-blind studies in many geographies again using the community-based studies – one could see such studies in South Africa, India and South America.

Any other comments?

“This is a much needed innovation to undertake a well-designed study in the community. We hope that it will be the first of many. We would also draw attention to the use of anti-viral therapies to be used in community based trials and to make use of the inhaled route of administration of such medicines that the FPM published in a blog last week – https://www.fpm.org.uk/blog/inhalation-therapies-for-covid-19/ “

‘Inhaled Budesonide in the Treatment of Early COVID-19 Illness: A Randomised Controlled Trial’ by Sanjay Ramakrishnan et al. is a Preprint with The Lancet and was posted on Monday 8 February.

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777194

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

None received.