Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers: A Randomized Clinical Trial.
Benjamin S. Abella,Eliana L. Jolkovsky,Barbara T. Biney,Julie E Uspal,Matthew C. Hyman,Ian Frank,Scott E. Hensley,Saar Gill,Dan T. Vogl,Ivan Maillard,Daria V. Babushok,Alexander C. Huang,Sunita D. Nasta,Jennifer C. Walsh,E. Paul Wiletyo,Phyllis A. Gimotty,Michael C. Milone,Ravi K. Amaravadi +17 more
TLDR
Among hospital-based health care workers, daily hydroxychloroquine did not prevent SARS-CoV-2 infection, although the trial was terminated early and may have been underpowered to detect a clinically important difference.Abstract:
Importance Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our knowledge, there is no effective pharmacologic prophylaxis for individuals at risk. Objective To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy. Design, Setting, and Participants This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants. Interventions Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks. Main Outcomes and Measures The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2–positive participants. Results Of the 132 randomized participants (median age, 33 years [range, 20-66 years]; 91 women [69%]), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 [6.3%] vs 4 of 61 [6.6%];P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%;P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%;P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, −9 to 17; vs placebo: 3 milliseconds; 95% CI, −5 to 11;P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered. Conclusions and Relevance In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19. Trial Registration ClinicalTrials.gov Identifier:NCT04329923read more
Citations
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COVID-19: breaking down a global health crisis.
Saad I. Mallah,Omar Ghorab,Sabrina Al-Salmi,Omar S. Abdellatif,Tharmegan Tharmaratnam,Tharmegan Tharmaratnam,Mina Amin Iskandar,Jessica Atef Nassef Sefen,Pardeep Sidhu,Bassam Atallah,Bassam Atallah,Rania El-Lababidi,Manaf AlQahtani +12 more
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TL;DR: Interventions that can be administered early during the course of infection to prevent disease progression and longer-term complications are urgently needed.
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Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial
Radha Rajasingham,Ananta S Bangdiwala,Melanie R. Nicol,Caleb P Skipper,Katelyn A Pastick,Margaret L Axelrod,Matthew F Pullen,Alanna A Nascene,Darlisha A. Williams,Nicole Engen,Elizabeth C Okafor,Brian I. Rini,Ingrid A. Mayer,Emily G. McDonald,Todd C. Lee,Peter Li,Lauren J. MacKenzie,Justin M. Balko,Stephen J. Dunlop,Katherine Huppler Hullsiek,David R. Boulware,Sarah M Lofgren,Covid Prep team +22 more
TL;DR: Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed CO VID-19 or COVID-19–compatible illness among healthcare workers.
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Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection : A Randomized Trial.
Ruanne V. Barnabas,Elizabeth R. Brown,Anna Bershteyn,Helen C. Stankiewicz Karita,Christine Johnston,Lorna E. Thorpe,Angelica Kottkamp,Kathleen M. Neuzil,Miriam K. Laufer,Meagan E. Deming,Michael K. Paasche-Orlow,Patricia Kissinger,Alfred Luk,Kristopher M Paolino,Raphael J. Landovitz,Risa M Hoffman,Torin T Schaafsma,Meighan Krows,Katherine K. Thomas,Susan Morrison,Harald S. Haugen,Lara Kidoguchi,Mark H. Wener,Alexander L. Greninger,Meei Li Huang,Keith R. Jerome,Anna Wald,Connie Celum,Helen Y. Chu,Jared M. Baeten +29 more
TL;DR: This randomized controlled trial tests hydroxychloroquine as postexposure prophylaxis for SARS-CoV-2 infection.
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COVID-19: immunopathology, pathophysiological mechanisms, and treatment options.
Larissa E. van Eijk,Mathijs Binkhorst,Arno R. Bourgonje,Annette K. Offringa,Douwe J. Mulder,Eelke M. Bos,Nikola Kolundzic,Nikola Kolundzic,Amaal Eman Abdulle,Peter H. J. van der Voort,Marcel G. M. Olde Rikkert,Johannes G. van der Hoeven,Wilfred F. A. den Dunnen,Jan-Luuk Hillebrands,Harry van Goor +14 more
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A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19.
David R. Boulware,Matthew F Pullen,Ananta S. Bangdiwala,Katelyn A Pastick,Sarah M Lofgren,Elizabeth C Okafor,Caleb P Skipper,Alanna A Nascene,Melanie R. Nicol,Mahsa Abassi,Nicole W. Engen,Matthew P. Cheng,Derek LaBar,Sylvain A. Lother,Lauren J. MacKenzie,Glen Drobot,Nicole Marten,Ryan Zarychanski,Lauren E. Kelly,Ilan S. Schwartz,Emily G. McDonald,Radha Rajasingham,Todd C. Lee,Kathy H. Hullsiek +23 more
TL;DR: After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid -19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.
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