Date: January 22nd, 2022

Reference: Yu et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet 2021

Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the #FOAMed project called First10EM.com.

Case: A 65-year-old woman with a history of diabetes, hypertension, and gastroesophageal reflux disease (GERD) presents with three days of fever, cough, and myalgias. She is fully vaccinated against COVID-19. Her husband tested positive for COVID-19 yesterday, and she used a home rapid test this morning that is also positive. Her vitals signs are all normal and she feels well enough to isolate at home. As you are preparing to discharge her, she asks if there is anything you can prescribe her to help. She thinks her friend might have been prescribed a puffer of some sort.

Background: I’ve tried not to focus too much on COVID-19. There are many great FOAMed resources that have done a good job of covering the topic. The SGEM has only done a few shows over the two years including:

* Debate regarding a universal mandate for masks early in the pandemic with Dr. Joe Vipond (SGEM Xtra: Masks4All in Canada Debate)

* Skeptical review of the early therapeutics with Dr. Sean Moore for the Canadian Association of Emergency Physicians (CAEP) Town Hall (SGEM Xtra: COVID19 Treatments – Be Skeptical)

* Diagnostic accuracy of various tests for COVID19 with Dr. Chris Carpenter (SGEM#299: Learning to Test for COVID19)

* Structured critical appraisal of the DANMASK trial with Dr. Joe Vipond (SGEM#309: That’s All Joe Asks of You – Wear a Mask)

The First10EM has done more than 30 blog posts about COVID-19 at this point, with a lot more to come. I know we all wish COVID-19 would just go away. But unfortunately, wishful thinking won’t help us, but hopefully science will. There is strong evidence that systemic steroids improve outcomes in patients with severe COVID-19 (First10EM: Steroids for COVID). This has raised the question of whether inhaled steroids might be helpful. After all, the infection is primarily in the lungs.

Early in the pandemic, there was some observational data that concluded that inhaled steroids were associated with an increased mortality from COVID-19 in patients with asthma and COPD (Schultze Lancet Resp Med 2020). However, the most likely explanation was not causal. Sicker patients are prescribed steroids more often, and so the association is not surprising.

The STOIC trial was an initial phase 2 open-label randomized control trial of inhaled budesonide for patients with mild symptoms of COVID-19 (Ramakrishnan et al Lancet Resp Med 2021). It did report positive results. Their primary outcome was a ‘COVID-19 related’ urgent care visit, emergency department assessment, or hospitalization, and was significantly reduced in the budesonide arm (15% vs 3%, p=0.009).

However, the unblinded trial design, less relevant composite outcome, and fact that the trial was stopped early limit confidence in the results. That bring us to the PRINCIPLE trial.