Platform Randomised trial of INterventions against COVID-19 in older peoPLE (PRINCIPLE): Protocol for a randomised, controlled, open-label, adaptive platform, trial of community treatment of COVID-19 syndromic illness in people at higher risk

Gail Hayward, Christopher C. Butler*, Ly Mee Yu, Benjamin R. Saville, Nicholas Berry, Jienchi Dorward, Oghenekome Gbinigie, Oliver Van Hecke, Emma Ogburn, Hannah Swayze, Emily Bongard, Julie Allen, Sharon Tonner, Heather Rutter, Sarah Tonkin-Crine, Aleksandra Borek, David Judge, Jenna Grabey, Simon De Lusignan, Nicholas P.B. ThomasPhilip H. Evans, Monique I. Andersson, Martin Llewelyn, Mahendra Patel, Susan Hopkins, F. D.Richard Hobbs

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Introduction: There is an urgent need to idenfy treatments for COVID-19 that reduce illness duration and hospital admission in those at higher risk of a longer illness course and complications. 

Methods and analysis: The Platform Randomised trial of INterventions against COVID-19 In older peoPLE trial is an open-label, multiarm, prospective, adaptive platform, randomised clinical trial to evaluate potential treatments for COVID-19 in the community. A master protocol governs the addition of new interventions as they become available, as well as the inclusion and cessation of existing intervention arms via frequent interim analyses. The first three interventions are hydroxychloroquine, azithromycin and doxycycline. Eligible participants must be symptomatic in the community with possible or confirmed COVID-19 that started in the preceding 14 days and either (1) aged 65 years and over or (2) aged 50-64 years with comorbidities. Recruitment is through general practice, health service helplines, COVID-19 'hot hubs' and directly through the trial website. Participants are randomised to receive either usual care or a study drug plus usual care, and outcomes are collected via daily online symptom diary for 28 days from randomisation. The research team contacts participants and/or their study partner following days 7, 14 and 28 if the online diary is not completed. The trial has two coprimary endpoints: time to first self-report of feeling recovered from possible COVID-19 and hospital admission or death from possible COVID-19 infection, both within 28 days from randomisation. Prespecified interim analyses assess efficacy or futility of interventions and to modify randomisation probabilities that allocate more participants to interventions with better outcomes. 

Ethics and dissemination: Ethical approval Ref: 20/SC/0158 South Central - Berkshire Research Ethics Committee; IRAS Project ID: 281958; EudraCT Number: 2020-001209-22. Results will be presented to policymakers and at conferences and published in peer-reviewed journals. Trial registration number ISRCTN86534580.

Original languageEnglish
JournalBMJ Open
Volume11
Issue number6
Early online date18 Jun 2021
DOIs
Publication statusE-pub ahead of print - 18 Jun 2021

Bibliographical note

Funding Information: Funding Platform Randomised trial of INterventions against COVID-19 In older peoPLE is funded by UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research. GH is funded by and NIHR Advanced Fellowship and by the NIHR MIC. JD and OG are funded by the Wellcome Trust PhD Programme for Primary Care Clinicians (216421/Z/19/Z and 203921/Z/16/Z, respectively).

Open Access: This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/.

Publisher Copyright: © Author(s) (or their employer(s)) 2021.

Citation: Hayward G, Butler CC, Yu L, et al. Platform Randomised trial of INterventions against COVID-19 In older peoPLE (PRINCIPLE): protocol for a randomised, controlled, open-label, adaptive platform, trial of community treatment of COVID-19 syndromic illness in people at higher risk. BMJ Open 2021;11:e046799.

DOI: 10.1136/bmjopen-2020-046799

Keywords

  • COVID-19
  • clinical trials
  • infectious diseases
  • primary care

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