Ivermectin for COVID-19 in adults in the community (PRINCIPLE): an open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes
dc.contributor.author | Hayward, G | |
dc.contributor.author | Yu, L-M | |
dc.contributor.author | Little, P | |
dc.contributor.author | Gbinigie, O | |
dc.contributor.author | Shanyinde, M | |
dc.contributor.author | Harris, V | |
dc.contributor.author | Dorward, J | |
dc.contributor.author | Saville, BR | |
dc.contributor.author | Berry, N | |
dc.contributor.author | Evans, PH | |
dc.contributor.author | Thomas, NP | |
dc.contributor.author | Patel, MG | |
dc.contributor.author | Richards, D | |
dc.contributor.author | Hecke, OV | |
dc.contributor.author | Detry, MA | |
dc.contributor.author | Saunders, C | |
dc.contributor.author | Fitzgerald, M | |
dc.contributor.author | Robinson, J | |
dc.contributor.author | Latimer-Bell, C | |
dc.contributor.author | Allen, J | |
dc.contributor.author | Ogburn, E | |
dc.contributor.author | Grabey, J | |
dc.contributor.author | de Lusignan, S | |
dc.contributor.author | Hobbs, FR | |
dc.contributor.author | Butler, CC | |
dc.contributor.author | PRINCIPLE Trial Collaborative Group | |
dc.date.accessioned | 2024-03-21T10:24:10Z | |
dc.date.issued | 2024-02-29 | |
dc.date.updated | 2024-03-21T08:42:21Z | |
dc.description.abstract | BACKGROUND: The evidence for whether ivermectin impacts recovery, hospital admissions, and longer-term outcomes in COVID-19 is contested. The WHO recommends its use only in the context of clinical trials. METHODS: In this multicentre, open-label, multi-arm, adaptive platform randomised controlled trial, we included participants aged ≥18 years in the community, with a positive SARS-CoV-2 test, and symptoms lasting ≤14 days. Participants were randomised to usual care, usual care plus ivermectin tablets (target 300-400 μg/kg per dose, once daily for 3 days), or usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery, and COVID-19 related hospitalisation/death within 28 days, analysed using Bayesian models. Recovery at 6 months was the primary, longer term outcome. TRIAL REGISTRATION: ISRCTN86534580. FINDINGS: The primary analysis included 8811 SARS-CoV-2 positive participants (median symptom duration 5 days), randomised to ivermectin (n=2157), usual care (n=3256), and other treatments (n=3398) from June 23, 2021 to July 1, 2022. Time to self-reported recovery was shorter in the ivermectin group compared with usual care (hazard ratio 1·15 [95% Bayesian credible interval, 1·07 to 1·23], median decrease 2.06 days [1·00 to 3·06]), probability of meaningful effect (pre-specified hazard ratio ≥1.2) 0·192). COVID-19-related hospitalisations/deaths (odds ratio 1·02 [0·63 to 1·62]; estimated percentage difference 0% [-1% to 0·6%]), serious adverse events (three and five respectively), and the proportion feeling fully recovered were similar in both groups at 6 months (74·3% and 71·2% respectively (RR = 1·05, [1·02 to 1·08]) and also at 3 and 12 months.,. INTERPRETATION: Ivermectin for COVID-19 is unlikely to provide clinically meaningful improvement in recovery, hospital admissions, or longer-term outcomes. Further trials of ivermectin for SARS-Cov-2 infection in vaccinated community populations appear unwarranted. FUNDING: UKRI / National Institute of Health Research (MC_PC_19079). | en_GB |
dc.description.sponsorship | National Institute for Health and Care Research (NIHR) | en_GB |
dc.identifier.citation | Vol. 88 (4), article 106130 | en_GB |
dc.identifier.doi | https://doi.org/10.1016/j.jinf.2024.106130 | |
dc.identifier.uri | http://hdl.handle.net/10871/135596 | |
dc.identifier | ORCID: 0000-0002-5277-3545 (Evans, Philip H) | |
dc.language.iso | en | en_GB |
dc.publisher | Elsevier / The British Infection Association | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/38431155 | en_GB |
dc.rights | © 2024 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). | en_GB |
dc.subject | COVID-19 | en_GB |
dc.subject | Ivermectin | en_GB |
dc.subject | SARS-Cov2 | en_GB |
dc.subject | clincial trial | en_GB |
dc.subject | long-term follow up | en_GB |
dc.title | Ivermectin for COVID-19 in adults in the community (PRINCIPLE): an open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2024-03-21T10:24:10Z | |
dc.identifier.issn | 0163-4453 | |
exeter.article-number | 106130 | |
exeter.place-of-publication | England | |
dc.description | This is the final version. Available on open access from Elsevier via the DOI in this record | en_GB |
dc.identifier.eissn | 1532-2742 | |
dc.identifier.journal | Journal of Infection | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_GB |
dcterms.dateAccepted | 2024-02-22 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2024-02-29 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2024-03-21T10:20:55Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2024-03-21T10:24:27Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2024-02-29 |
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Except where otherwise noted, this item's licence is described as © 2024 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).