Inhaled Budesonide for COVID-19 in People at High Risk
- Inhaled budesonide reduced time to recovery, with a high probability of also reducing COVID-19–related hospital admissions or deaths by an absolute difference of 2% for people at higher risk of hospital admission and death with COVID-19 in the community.
- Based on these data, inhaled budesonide may be considered for patients with COVID-19 who are at higher risk of complications in the community.
- Additional studies are also needed to establish the effect of budesonide among fully vaccinated people with COVID-19.
What is the effectiveness of inhaled budesonide in reducing recovery time and rates of coronavirus disease 2019 (COVID-19)–related hospital admission or death in people at high risk of an adverse outcome in the community?
The investigators conducted PRINCIPLE, a multicenter, open-label, multiarm, randomized, controlled, adaptive platform trial done remotely from a central trial site and at primary care centers in the United Kingdom. Eligible participants were aged ≥65 years or ≥50 years with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to the hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 μg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analyzed using Bayesian models. The primary analysis population included all eligible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–positive patients randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing.
The trial began enrollment on April 2, 2020, with randomization to budesonide from November 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. A total of 4,700 participants were randomly assigned to budesonide (n = 1,073), usual care alone (n = 1,988), or other treatments (n = 1,639). The primary analysis model included 2,530 SARS-CoV-2–positive participants, with 787 in the budesonide group, 1,069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2.94 days (95% Bayesian credible interval [BCI], 1.19-5.12) in the budesonide group versus the usual care group (11.8 days [95% BCI, 10.0-14.1] vs. 14.7 days [12.3-18.0]; hazard ratio, 1.21 [95% BCI, 1.08-1.36]), with a probability of superiority >0.999, meeting the prespecified superiority threshold of 0.99. For the hospital admission or death outcome, the estimated rate was 6.8% (95% BCI, 4.1-10.2) in the budesonide group versus 8.8% (5.5-12.7) in the usual care group (estimated absolute difference, 2.0% [95% BCI, –0.2 to 4.5]; odds ratio, 0.75 [95% BCI, 0.55-1.03]), with a probability of superiority 0.963, below the prespecified superiority threshold of 0.975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19).
The authors concluded that inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although results did not meet the superiority threshold) in people with COVID-19 in the community who are at higher risk of complications.
This open-label randomized study reports that inhaled budesonide reduced time to recovery by 3 days, with a high probability of also reducing COVID-19–related hospital admissions or deaths by an absolute difference of 2% for people at higher risk of hospital admission and death with COVID-19 in the community. Reducing time to recovery is an important patient-specific outcome, and potential prevention of hospital admissions or deaths would lessen the burden on hospitals during COVID-19 surges. Based on these data, inhaled budesonide may be considered for patients with COVID-19 who are at higher risk of complications in the community. Additional studies are also needed to establish the effect of budesonide among fully vaccinated people with COVID-19.
Clinical Topics: Prevention
Keywords: Anti-Asthmatic Agents, Bronchodilator Agents, Budesonide, Comorbidity, Coronavirus, COVID-19, Patient Admission, Primary Prevention, Primary Health Care, Risk, SARS-CoV-2, Vaccination
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