ניסוי קליני שכלל טיפול באמצעות בודזונייד בשאיפה בחולי קורונה בסיכון גבוה, הראה שיפור משמעותי בזמני החלמה, שיעורי אשפוז ותמותה.

ממצאים עיקריים

ניסויים קליניים שנערכו בבריטניה. המחקר כלל 4,700 חולי קורונה לא מאושפזים מעל גיל 65, או מעל גיל 50 אם הם סבלו ממחלות נוספות.

1,073 מטופלים קיבלו 800 מק"ג בודזונייד בשאיפה, פעמיים ביום; ל-1,988 מטופלים ניתן טיפול דומה ללא תרופות, ול-1,639 ניתן טיפול דומה אך גם תרופות אחרות. המטופלים נטלו בודזונייד בשאיפה פעמיים ביום במשך 14 יום, ונותרו במעקב במשך 28 יום.

מטופלים שטופלו בבודזונייד החלימו בממוצע כמעט תשעה ימים מהר יותר ממטופלים שלא טופלו בבודזונייד.

בנוסף, שיעורי האשפוז והתמותה של מטופלים בבודזונייד היו נמוכים בכ-30% ממטופלים שלהם ניתנו תרופות אחרות, או שלא קיבלו תרופות בכלל.

The Lancet

Publication Date: אוגוסט 10, 2021
Peer Reviewed: Yes
Publication Type: Original | Clinical Prospective
DOI: https://www.doi.org/10.1016/S0140-6736(21)01744-X

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

Ly-Mee Yu, Mona Bafadhel, Jienchi Dorward, Gail Hayward, Benjamin R Saville, Oghenekome Gbinigie, Oliver Van Hecke, Emma Ogburn, Philip H Evans, Nicholas P B Thomas, Mahendra G Patel, Duncan Richards, Nicholas Berry, Michelle A Detry, Christina Saunders, Mark Fitzgerald, Victoria Harris, Milensu Shanyinde, Simon de Lusignan, Monique I Andersson, Peter J Barnes, Richard E K Russell, Dan V Nicolau, Sanjay Ramakrishnan, F D Richard Hobbs, Christopher C Butler, Ly-Mee Yu, Mona Bafadhel, Jienchi Dorward, Gail Hayward, Benjamin R Saville, Oghenekome Gbinigie, Oliver van Hecke, Emma Ogburn, Philip H Evans, Nicholas PB Thomas, Mahendra G Patel, Duncan Richards, Nicholas Berry, Michelle A Detry, Christina T Saunders, Mark Fitzgerald, Victoria Harris, Milensu Shanyinde, Simon de Lusignan, Monique I Andersson, Peter J Barnes, Richard EK Russell, Dan V Nicolau, Sanjay Ramakrishnan, FD Richard Hobbs, Christopher C Butler

Abstract

Background
A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community.

Methods
PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to 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, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants 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.

Findings
The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 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 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 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 to 10·2) in the budesonide group versus 8·8% (5·5 to 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 to 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).

Interpretation
Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications.