Acceptability of a COVID-19 pre-exposure prophylaxis trial with hydroxychloroquine in French healthcare workers during the first wave of COVID-19 pandemic

Amandine Gagneux-Brunon; Clémentine Schilte; Arnauld Garcin; Nathalie Jolly; Muriel Vray; Laura Schaeffer; Xavier Duval; Bruno Hoen; Elisabeth Botelho-Nevers

Acceptability of a COVID-19 pre-exposure prophylaxis trial with hydroxychloroquine in French healthcare workers during the first wave of COVID-19 pandemic

Gagneux-Brunon et al., Trials, doi:10.1186/s13063-021-05329-y, NCT04328285, Mar 2022

HCQ for COVID-19

1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.

Lower risk for mortality, hospitalization, progression, recovery, cases, and viral clearance.

No treatment is 100% effective. Protocols combine treatments.

6,300+ studies for 210+ treatments. c19early.org

Meta Analysis

118 participant HCQ prophylaxis RCT with results not reported over 3 years after completion.

37 HCQ RCTs have results missing long after expected1-37
The trials report a total of 20,747 patients, with 11 trials having actual enrollment of 3,487, and the remainder estimated.

Important missing comments or errors? Let us know.

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10. Nanni et al., PROTECT Trial: A cluster-randomized study with hydroxychloroquine versus observational support for prevention or early-phase treatment of Coronavirus disease (COVID-19): A structured summary of a study protocol for a randomized controlled trial, Trials, doi:10.1186/s13063-020-04527-4.biomedcentral.com, doi.org.

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12. Kara et al., Efficacy and Safety of Hydroxychloroquine and Favipiravir in the Treatment of Mild to Moderate COVID-19, NCT04411433, clinicaltrials.gov/study/NCT04411433clinicaltrials.gov.

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14. Moraes et al., Comparative Study of Hydroxychloroquine and Ivermectin in COVID-19 Prophylaxis, NCT04384458, clinicaltrials.gov/study/NCT04384458clinicaltrials.gov.

15. Borrie et al., COVID-19 PEP- High-risk Individuals in Long-term and Specialized Care - Canada, NCT04397328, clinicaltrials.gov/study/NCT04397328clinicaltrials.gov.

16. James et al., PROLIFIC ChemoprophylaxisTrial (COVID-19), NCT04352933, clinicaltrials.gov/study/NCT04352933clinicaltrials.gov.

17. Morales-Asencio et al., Prevention of COVID19 Infection in Nursing Homes by Chemoprophylaxis With Hydroxychloroquine, NCT04400019, clinicaltrials.gov/study/NCT04400019clinicaltrials.gov.

18. Mordmüller et al., Hydroxychloroquine for COVID-19 (COV-HCQ), NCT04342221, clinicaltrials.gov/study/NCT04342221clinicaltrials.gov.

19. Gül et al., Clinical Trial For Early SARS-CoV-2 (COVID-19) Treatment, NCT04981379, clinicaltrials.gov/study/NCT04981379clinicaltrials.gov.

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21. Okasha et al., Hydroxychloroquine and Nitazoxanide Combination Therapy for COVID-19, NCT04361318, clinicaltrials.gov/study/NCT04361318clinicaltrials.gov.

22. Levi et al., Open Label Study to Compare Efficacy, Safety and Tolerability of Hydroxychloroquine Combined With Azithromycin Compared to Hydroxychloroquine Combined With Camostat Mesylate and to "no Treatment" in SARS CoV 2 Virus (COSTA), NCT04355052, clinicaltrials.gov/study/NCT04355052clinicaltrials.gov.

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Gagneux-Brunon et al., 30 Mar 2022, Double Blind Randomized Controlled Trial, placebo-controlled, France, peer-reviewed, study period 14 April, 2020 - 30 March, 2022, trial NCT04328285 (history). Contact: elisabeth.botelho-nevers@chu-saint-etienne.fr (corresponding author), Arnauld.Garcin@chu-st-etienne.fr, nathalie.jolly@pasteur.fr.

Abstract: Gagneux-Brunon et al. Trials (2021) 22:373 https://doi.org/10.1186/s13063-021-05329-y LETTER Open Access Acceptability of a COVID-19 pre-exposure prophylaxis trial with hydroxychloroquine in French healthcare workers during the first wave of COVID-19 pandemic Amandine Gagneux-Brunon1,2, Clémentine Schilte3, Arnauld Garcin4, Nathalie Jolly3, Muriel Vray5, Laura Schaeffer5, Xavier Duval6, Bruno Hoen7 and Elisabeth Botelho-Nevers1,2* Keywords: Pre-exposure chemoprophylaxis trial, SARS-CoV-2 infection, Healthcare workers, Acceptability, Hydroxychloroquine Healthcare workers (HCWs) have been over-represented among people infected with Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). In France, between March 1 and November 2, 2020, SARS-CoV-2 infection was diagnosed in more than 44,000 HCWs and killed 17 [1]. In the USA, HCWs accounted for around 20% of the confirmed cases of SARS-CoV-2 infections by April 2020 [2]. Protection of HCWs rapidly became a crucial challenge during the COVID-19 pandemics [3]. Pre- and post-exposure chemoprophylaxis was considered to be used in addition to personal protective equipment. More than 50 clinical trials aiming to assess chloroquine or hydroxychloroquine (HCQ) in HCWs and/or household contacts of COVID-19 cases have been registered worldwide with ClinicalTrials.gov. In France in April 2020, a multi-center randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a 2-month pre-exposure prophylaxis with HCQ in 600 HCWs exposed to COVID-19 patients was started [4]. This trial was funded by the French hospital program for clinical research (PHRC) and sponsored by * Correspondence: elisabeth.botelho-nevers@chu-saint-etienne.fr 1 Department of Infectious diseases, University Hospital of Saint-Etienne, Saint-Etienne, 42055, France 2 CIC-1408 Vaccinology, INSERM, University Hospital of Saint-Etienne, Saint-Etienne, 42055, France Full list of author information is available at the end of the article the University Hospital of Saint-Etienne in collaboration with Institut Pasteur in Paris. For each participant, six visits at the investigation center, one weekly electrocardiogram, 5 blood samplings, and 4 nasopharyngeal swabs for SARS-CoV-2 RT-PCR were scheduled. Before the trial started, we conducted an anonymous online survey in ten of the investigation centers to evaluate the acceptability of the trial among HCWs, whether they worked in a hospital, an ambulatory setting, or a long-term care facility. Eight hundred and seventy-one HCWs completed the survey. Among respondents, 695 (79.8%) reported they were interested in participating in the trial. Intention to participate was not influenced by age or working place. Among the 695 potential volunteers, 430 (61.9%) were under 45 years of age and only 126 (18.1%) reported a significant comorbidity. The main reasons for declining participation in the study were the following: (1) fears about HCQ side effects in 121 of the 176 decliners (68.8%), (2) the perception that the individual risk of severe COVID-19 was low in 36 (20.5%), (3) the constraints resulting from the number of study visits in 29 (16.5%), and (4) the burden of nasopharyngeal swabs for SARS-CoV-2 RT-PCR in 25 (14.2%). Six hundred and ninety-five respondents reported being interested in participating in the chemoprophylaxis trial, and 117 were actually enrolled by May 27, 2020. In the first center where the trial was started, 342 HCWs reported being © The Author(s)...

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