Abstract: Open access Original research To cite: Tirupakuzhi Vijayaraghavan BK, Jha V, Rajbhandari D, et al. Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratory-­ confirmed COVID-­19 infections among healthcare workers: a multicentre, parallel-­group randomised controlled trial from India. BMJ Open 2022;12:e059540. doi:10.1136/ bmjopen-2021-059540 ► Prepublication history and additional supplemental material for this paper are available online. To view these files, please visit the journal online (http://dx.doi.org/10.1136/​ bmjopen-2021-059540). Received 24 November 2021 Accepted 13 May 2022 © Author(s) (or their employer(s)) 2022. Re-­use permitted under CC BY-­NC. No commercial re-­use. See rights and permissions. Published by BMJ. For numbered affiliations see end of article. Correspondence to Dr Bharath Kumar Tirupakuzhi Vijayaraghavan; ​bharathkumartv@​gmail.c​ om Bharath Kumar Tirupakuzhi Vijayaraghavan ‍ ‍,1,2 Vivekanand Jha,2 Dorrilyn Rajbhandari,3 Sheila Nainan Myatra,4,5 Arpita Ghosh ‍ ‍,2 Amritendu Bhattacharya,2 Sumaiya Arfin,2 Abhinav Bassi,2 Lachlan Hugh Donaldson,3 Naomi E Hammond ‍ ‍,6 Oommen John,2 Rohina Joshi,7 Mallikarjuna Kunigari,2 Cynthia Amrutha,8 Syed Haider Mehdi Husaini,9 Subir Ghosh,10 Santosh Kumar Nag,11 Hari Krishnan Selvaraj,12 Viny Kantroo,13 Kamal D Shah,14 Balasubramanian Venkatesh,3,15,16 for the HOPE Investigators ABSTRACT Objectives To determine whether hydroxychloroquine when used with personal protective equipment reduces the proportion of laboratory-­confirmed COVID-­19 among healthcare workers in comparison to the use of personal protective equipment alone. Design Multicentre, parallel-­group, open-­label randomised trial. Enrolment started on 29 June 2020 and stopped on 4 February 2021. Participants randomised in HydrOxychloroquine Prophylaxis Evaluation were followed for 6 months. Setting 9 hospitals across India. Participants Healthcare workers in an environment with exposure to COVID-­19 were randomised in a 1:1 ratio to hydroxychloroquine plus use of personal protective equipment or personal protective equipment alone. 886 participants were screened and 416 randomised (213 hydroxychloroquine arm and 203 personal protective equipment). Intervention Participants in intervention arm received 800 mg of hydroxychloroquine on day of randomisation and then 400 mg once a week for 12 weeks in addition to the use of personal protective equipment. In the control arm, participants continued to use personal protective equipment alone. Main outcome Proportion of laboratory-­confirmed COVID-­19 in the 6 months after randomisation. Results Participants were young (mean age 32.1 years, SD 9.1 years) with low-­comorbid burden. 47.4% were female. In the 6 months after randomisation (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary STRENGTHS AND LIMITATIONS OF THIS STUDY ⇒ Our trial is the largest multicentre trial evaluating hydroxychloroquine prophylaxis for COVID-­19 from a low and middle-­income country setting. ⇒ The trial tested the dose of hydroxychloroquine recommended by the Indian regulatory agencies and had the longest follow-­up duration among hydroxychloroquine trials. ⇒ Our trial included a diverse set of participants, both in terms of balance of men and women, but also in terms of the various healthcare..