Evidence map›Paper›PMID 34388395›Full record

Trial reportLancet (London, England)2021

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 and 17 more

Erratum issuedOpen access · hybridAbstract readMulticenter StudyPragmatic Clinical TrialRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 180 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
180citing papers in PubMed, 13 pooled it
30.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

180 citing papers in PubMed, 13 syntheses or guidelines pooled it, 303 citations in OpenAlex.

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  7. Inhaled corticosteroids' effect on COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.Canadian journal of respiratory therapy : CJRT = Revue canadienne de la therapie respiratoire : RCTR · 2023
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  8. Risk of serious COVID-19 outcomes among adults and children with moderate-to-severe asthma: a systematic review and meta-analysis.European respiratory review : an official journal of the European Respiratory Society · 2022
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  11. Inhaled corticosteroids for the treatment of COVID-19.The Cochrane database of systematic reviews · 2022
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120 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

27 authors at 7 institutions in 4 countries.

Ly-Mee YuNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Mona BafadhelNuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Jienchi DorwardNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK; Centre for the AIDS Programme of Research in South Africa, University of KwaZulu-Natal, Durban, South Africa.
Gail HaywardNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Benjamin R SavilleBerry Consultants, Austin, TX, USA; Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, USA.
Oghenekome GbinigieNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Oliver Van HeckeNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Emma OgburnNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Philip H EvansCollege of Medicine and Health, University of Exeter, Exeter, UK; National Institute for Health Research Clinical Research Network, National Institute for Health Research, London, UK.
Nicholas P B ThomasNational Institute for Health Research Clinical Research Network, National Institute for Health Research, London, UK; Royal College of General Practitioners, London, UK.
Mahendra G PatelNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Duncan RichardsOxford Clinical Trials Research Unit, Botnar Research Centre, University of Oxford, Oxford, UK.
Nicholas BerryBerry Consultants, Austin, TX, USA.
Michelle A DetryBerry Consultants, Austin, TX, USA.
Christina SaundersBerry Consultants, Austin, TX, USA.
Mark FitzgeraldBerry Consultants, Austin, TX, USA.
Victoria HarrisNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Milensu ShanyindeNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Simon de LusignanNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Monique I AnderssonNuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Peter J BarnesNational Heart and Lung Institute, Imperial College, London, UK.
Richard E K RussellNuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
Dan V NicolauNuffield Department of Clinical Medicine, University of Oxford, Oxford, UK; UQ Centre for Clinical Research, University of Queensland, Brisbane, QLD, Australia.
Sanjay RamakrishnanNational Institute for Health Research Oxford Biomedical Research Centre, Oxford, UK.
F D Richard HobbsNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. Electronic address: richard.hobbs@phc.ox.ac.uk.
Christopher C ButlerNuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK. Electronic address: christopher.butler@phc.ox.ac.uk.
PRINCIPLE Trial Collaborative Group
University of Oxford · GBRoyal College of General Practitioners · GBImperial College London · GBUniversity of Queensland · AUBerry & Associates (United States) · USNational Institute for Health Research · GBUniversity of KwaZulu-Natal · ZA

Funding

Medical Research Council MC_PC_19079
6 · The paper itself

Abstract

backgroundA 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.

methodsPRINCIPLE 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.

findingsThe 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).

interpretationInhaled 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.

fundingNational Institute of Health Research and United Kingdom Research Innovation.

Indexed as

COVID-19 Drug TreatmentAdministration, InhalationAgedBayes TheoremBudesonideCOVID-19FemaleGlucocorticoidsHospitalizationHumansMaleMiddle AgedProspective StudiesRisk FactorsSARS-CoV-2Treatment OutcomeBudesonideGlucocorticoids

Identifiers

PMID34388395
PMCPMC8354567
OpenAlexW3188676168

What OpenQuestion holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.