Conv. Plasma
Nigella Sativa

All HCQ studies
Meta analysis
study COVID-19 treatment researchHCQHCQ (more..)
Melatonin Meta
Metformin Meta
Antihistamines Meta
Azvudine Meta Molnupiravir Meta
Bromhexine Meta
Budesonide Meta
Colchicine Meta Nigella Sativa Meta
Conv. Plasma Meta Nitazoxanide Meta
Curcumin Meta Paxlovid Meta
Famotidine Meta Quercetin Meta
Favipiravir Meta Remdesivir Meta
Fluvoxamine Meta Thermotherapy Meta
Hydroxychlor.. Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   

Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: A randomized, multicenter, placebo-controlled trial (HERO-HCQ)

Naggie et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2023.01.019 (date from preprint), HERO-HCQ, NCT04334148
Aug 2021  
  Source   PDF   All Studies   Meta AnalysisMeta
Symp. case 24% Improvement Relative Risk Symp. case, MH 29% Symp. case, PCR+ 51% Symp. case, pooled 26% HCQ  HERO-HCQ  Prophylaxis  DB RCT Is pre-exposure prophylaxis with HCQ beneficial for COVID-19? Double-blind RCT 1,359 patients in the USA (April - November 2020) Fewer symptomatic cases with HCQ (not stat. sig., p=0.18) Naggie et al., Int. J. Infectious Dise.., Aug 2021 FavorsHCQ Favorscontrol 0 0.5 1 1.5 2+
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
*, now with p < 0.00000000001 from 411 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
HCQ prophylaxis RCT reporting statistically significant lower cases when pooling results with the COVID PREP RCT, OR 0.74 [0.55-1.0] p = 0.046. There were no significant safety issues.
The trials were both terminated early resulting in a loss of power, however the combination shows statistically significant efficacy of HCQ. Note that this result has been censored in the journal version, see1. The journal paper still shows the COVID PREP paper in the reference list, but the analysis and discussion has been deleted.
The journal version falsely states: "The prophylactic use of HCQ by HCW was safe but not effective", whereas the paper actually estimates OR 0.75, which becomes statistically significant OR 0.74 when pooled with COVID PREP.
The preprint contains a different version: "...but did not produce a clinically useful treatment". It's unclear why ~25% fewer cases would not be useful.
They also state "This is one of several negative studies", however the result is positive, just not reaching statistical significance before pooling with COVID PREP.
risk of symptomatic case, 23.5% lower, RR 0.76, p = 0.18, treatment 41 of 683 (6.0%), control 53 of 676 (7.8%), NNT 54, odds ratio converted to relative risk, logistic regression.
risk of symptomatic case, 29.3% lower, RR 0.71, p = 0.18, treatment 41 of 683 (6.0%), control 53 of 676 (7.8%), NNT 54, odds ratio converted to relative risk, Mantel-Haenszel.
risk of symptomatic case, 50.5% lower, RR 0.49, p = 0.34, treatment 3 of 683 (0.4%), control 6 of 676 (0.9%), NNT 223, PCR confirmed.
risk of symptomatic case, 26.0% lower, OR 0.74, p = 0.046, pooled results with COVID-PREP, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Naggie et al., 25 Aug 2021, Double Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, mean age 43.6, 23 authors, study period April 2020 - November 2020, trial NCT04334148 (history) (HERO-HCQ). Contact:
This PaperHCQAll
Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine (HERO-HCQ)
MD, MHS Susanna Naggie, MD, MHS b Aaron Milstone, MD, MPH c , Mario Castro, MD Sean P Collins, MD e , Deverick Seetha Lakshmi, Deverick J Anderson, MD g , Lizbeth Cahuayme-Zuniga, BS Kisha Batey Turner, MA Lauren W Cohen, MD h , Judith Currier, RN, BSN a , Elizabeth Fraulo, MD Anne Friedland, MS a , Jyotsna Garg, RTT, MPA i Anoop George, PhD Hillary Mulder, RN, MS, MBA a , Rachel E Olson, PhD Emily C O'brien, MD, MPP d Russell L Rothman, PhD Elizabeth Shenkman, MBA a , Jack Shostak, MD a , Christopher W Woods, PhD Kevin J Anstrom, MD, MHS a , Adrian F Hernandez
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2023.01.019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
DISCUSSION Statement of Principal Findings The study was not powered to detect a small beneficial effect and the test of the primary endpoint does not provide evidence of a benefit for HCQ for PrEP in a high-risk HCW population. Strengths and Weaknesses in Context The original study design was powered to show a 20% relative treatment effect assuming a 5% event rate in the placebo arm. However, due to slowed enrollment early in the study, the study was amended to decrease the sample size and hence the power, increasing the detectable relative treatment effect to 50%. Thus, the study was not powered to detect a small treatment effect. This outcome was not unique to this randomized trial; a 2021 analysis concluded that among the early COVID-19 studies, only 5% were both randomized and adequately powered [24] . While the partially remote nature of the trial was novel and improved feasibility during a pandemic, it also resulted in the limitation that we did not have laboratory confirmation for COVID-19-like illness. Early in the pandemic, in some regions, testing was not performed per local policies in HCW with suspected infection and mild or moderate symptoms. Per the study protocol, these events were defined as suspected cases and were combined with the confirmed cases in the primary composite outcome. This resulted in few confirmed COVID-19 infections; thus, our primary outcome was primarily comprised of suspected COVID-19 clinical infections. While the study did not have..
Abella, Jolkovsky, Biney, Uspal, Hyman, Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers: a randomized clinical trial, JAMA internal medicine
Arroll, Goodyear-Smith, Crengle, Gunn, Kerse et al., Validation of PHQ-2 and PHQ-9 to screen for major depression in the primary care population, Ann Fam Med, doi:10.1370/afm.1139
Bugin, Woodcock, Trends in COVID-19 therapeutic clinical trials, Nat Rev Drug Discov, doi:10.1038/d41573-021-00037-3
Cdc Covid-, Characteristics of health care personnel with COVID-19 -United States, February 12, MMWR Morb Mortal Wkly Rep, doi:10.15585/mmwr.mm6915e6
Cochran, Some methods for strengthening the common X2 tests, Biometrics, doi:10.2307/3001616
Dolan, Mohr, Lempa, Joos, Fihn et al., Using a single item to measure burnout in primary care staff: a psychometric evaluation, J Intern Med, doi:10.1007/s11606-014-3112-6
Forrest, Mctigue, Hernandez, Cohen, Cruz et al., PCORnet® 2020: current state, accomplishments, and future directions, J Clin Epidemiol, doi:10.1016/j.jclinepi.2020.09.036
Forrest, Xu, Thomas, Webb, Cohen et al., Registry Research Group. Impact of the early phase of the COVID-19 pandemic on US healthcare workers: results from the HERO Registry, J Gen Intern Med, doi:10.1007/s11606-020-06529-z
Fox, Mechanism of action of hydroxychloroquine as an antirheumatic drug, Semin Arthritis Rheum, doi:10.1016/s0049-0172
Friedland, Hernandez, Anstrom, Ml, Cohen, Design of the Healthcare Worker Exposure Response and Outcomes (HERO) research platform, Contemp Clin Trials, doi:10.1016/j.cct.2021.106525
Garner, Constructing confidence intervals for the differences of binomial proportions in SAS®
Grau-Pujol, Camprubí-Ferrer, Marti-Soler, Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial, Trials, doi:10.1186/s13063-021-05758-9
Kalil, Treating COVID-19-off-label drug use, compassionate use, and randomized clinical trials during pandemics, JAMA, doi:10.1001/jama.2020.4742
Keyaerts, Vijgen, Maes, Neyts, Van Ranst, In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2004.08.085
Kroenke, Spitzer, Williams, The Patient Health Questionnaire-2: validity of a twoitem depression screener, Med Care, doi:10.1097/01.MLR.0000093487.78664.3C
Lazarus, Wyka, White, Picchio, Rabin, Revisiting COVID-19 vaccine hesitancy around the world using data from 23 countries in 2021, Nat Commun, doi:10.1038/s41467-022-31441-x
Liu, Cao, Xu, Wang, Zhang, Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro, Cell Discov, doi:10.1038/s41421-020-0156-0
Mcchesney, Conway, Banks, Jr, Rogers, Shekosky Studies of the metabolism of some compounds of the 4-amino-7-chloroquinoline series, J Pharmacol Exp Ther
Mccreary, Pogue, COVID-19 treatment: a review of early and emerging options, Open Forum Infect Dis, doi:10.1093/ofid/ofaa105
Mckinnon, Wang, Zervos, Saval, Marshall-Nightengale, Safety and tolerability of hydroxychloroquine in health care workers and first responders for the prevention of COVID-19: WHIP COVID-19 Study, International Journal of Infectious Diseases
Mcmurray, Linzer, Konrad, Douglas, Shugerman et al., The work lives of women physicians results from the physician work life study. The SGIM Career Satisfaction Study Group, J Gen Intern Med, doi:10.1111/j.1525-1497.2000.im9908009.x
Monrad, Quaade, Powell-Jackson, Supply, then demand? Health expenditure, political leanings, cost obstacles to care, and vaccine hesitancy predict statelevel COVID-19 vaccination rates, Vaccine, doi:10.1016/j.vaccine.2022.08.050
Naggie, Milstone, Castro, Collins, Lakshmi, Hydroxychloroquine for preexposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial (HERO-HCQ), medRxiv
Pilkonis, Choi, Reise, Stover, Riley et al., Item banks for measuring emotional distress from the Patient-Reported Outcomes Measurement Information System (PROMIS®): depression, anxiety, and anger, Assessment, doi:10.1177/1073191111411667
Rajasingham, Bangdiwala, Nicol, Skipper, Pastick et al., PREP Team. Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial, Clin Infect Dis, doi:10.1093/cid/ciaa1571
Rohland, Kruse, Rohrer, Validation of a single-item measure of burnout against the Maslach Burnout Inventory among physicians, Stress Health, doi:10.1002/smi.1002
Rojas-Serrano, Portillo-Vásquez, Thirion-Romero, Vázquez-Pérez, Mejía-Nepomuceno et al., Hydroxychloroquine for prophylaxis of COVID-19 in health workers: a randomized clinical trial, Posted, doi:10.1101/2021.05.14.21257059v1
Tett, Clinical pharmacokinetics of slow-acting antirheumatic drugs, Clin Pharmacokinet, doi:10.2165/00003088
Vincent, Bergeron, Benjannet, Erickson, Rollin, Chloroquine is a potent inhibitor of SARS coronavirus infection and spread, Virol J, doi:10.1186/1743-422X-2-69
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res, doi:10.1038/s41422-020-0282-0
West, Dyrbye, Sloan, Shanafelt, Single item measures of emotional exhaustion and depersonalization are useful for assessing burnout in medical professionals, J Gen Intern Med, doi:10.1007/s11606-009-1129-z
Yao, Ye, Zhang, Cui, Huang, In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Clin Infect Dis, doi:10.1093/cid/ciaa237
{ 'indexed': {'date-parts': [[2023, 1, 20]], 'date-time': '2023-01-20T05:53:39Z', 'timestamp': 1674194019435}, 'reference-count': 0, 'publisher': 'Elsevier BV', 'license': [ { 'start': { 'date-parts': [[2023, 1, 1]], 'date-time': '2023-01-01T00:00:00Z', 'timestamp': 1672531200000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': ''}, { 'start': { 'date-parts': [[2023, 1, 12]], 'date-time': '2023-01-12T00:00:00Z', 'timestamp': 1673481600000}, 'content-version': 'vor', 'delay-in-days': 11, 'URL': ''}], 'content-domain': { 'domain': [ '', '', '', '', '', '', '', ''], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2023, 1]]}, 'DOI': '10.1016/j.ijid.2023.01.019', 'type': 'journal-article', 'created': {'date-parts': [[2023, 1, 20]], 'date-time': '2023-01-20T03:42:09Z', 'timestamp': 1674186129000}, 'update-policy': '', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: A ' 'randomized, multicenter, placebo-controlled trial (HERO-HCQ)', 'prefix': '10.1016', 'author': [ { 'ORCID': '', 'authenticated-orcid': False, 'given': 'Susanna', 'family': 'Naggie', 'sequence': 'first', 'affiliation': []}, {'given': 'Aaron', 'family': 'Milstone', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mario', 'family': 'Castro', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sean P.', 'family': 'Collins', 'sequence': 'additional', 'affiliation': []}, {'given': 'Seetha', 'family': 'Lakshmi', 'sequence': 'additional', 'affiliation': []}, {'given': 'Deverick J.', 'family': 'Anderson', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': '', 'authenticated-orcid': False, 'given': 'Lizbeth', 'family': 'Cahuayme-Zuniga', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kisha Batey', 'family': 'Turner', 'sequence': 'additional', 'affiliation': []}, {'given': 'Lauren W.', 'family': 'Cohen', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': '', 'authenticated-orcid': False, 'given': 'Judith', 'family': 'Currier', 'sequence': 'additional', 'affiliation': []}, {'given': 'Elizabeth', 'family': 'Fraulo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anne', 'family': 'Friedland', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jyotsna', 'family': 'Garg', 'sequence': 'additional', 'affiliation': []}, {'given': 'Anoop', 'family': 'George', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': '', 'authenticated-orcid': False, 'given': 'Hillary', 'family': 'Mulder', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rachel E.', 'family': 'Olson', 'sequence': 'additional', 'affiliation': []}, {'given': 'Emily C.', 'family': "O'Brien", 'sequence': 'additional', 'affiliation': []}, { 'ORCID': '', 'authenticated-orcid': False, 'given': 'Russell L.', 'family': 'Rothman', 'sequence': 'additional', 'affiliation': []}, {'given': 'Elizabeth', 'family': 'Shenkman', 'sequence': 'additional', 'affiliation': []}, {'given': 'Jack', 'family': 'Shostak', 'sequence': 'additional', 'affiliation': []}, {'given': 'Christopher W.', 'family': 'Woods', 'sequence': 'additional', 'affiliation': []}, {'given': 'Kevin J.', 'family': 'Anstrom', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': '', 'authenticated-orcid': False, 'given': 'Adrian F.', 'family': 'Hernandez', 'sequence': 'additional', 'affiliation': []}], 'member': '78', 'container-title': 'International Journal of Infectious Diseases', 'original-title': [], 'language': 'en', 'link': [ { 'URL': '', 'content-type': 'text/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': '', 'content-type': 'text/plain', 'content-version': 'vor', 'intended-application': 'text-mining'}], 'deposited': { 'date-parts': [[2023, 1, 20]], 'date-time': '2023-01-20T03:42:10Z', 'timestamp': 1674186130000}, 'score': 1, 'resource': {'primary': {'URL': ''}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 1]]}, 'references-count': 0, 'alternative-id': ['S120197122300019X'], 'URL': '', 'relation': {}, 'ISSN': ['1201-9712'], 'subject': ['Infectious Diseases', 'Microbiology (medical)', 'General Medicine'], 'container-title-short': 'International Journal of Infectious Diseases', 'published': {'date-parts': [[2023, 1]]}, 'assertion': [ {'value': 'Elsevier', 'name': 'publisher', 'label': 'This article is maintained by'}, { 'value': 'Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care ' 'workers: A randomized, multicenter, placebo-controlled trial (HERO-HCQ)', 'name': 'articletitle', 'label': 'Article Title'}, { 'value': 'International Journal of Infectious Diseases', 'name': 'journaltitle', 'label': 'Journal Title'}, { 'value': '', 'name': 'articlelink', 'label': 'CrossRef DOI link to publisher maintained version'}, {'value': 'article', 'name': 'content_type', 'label': 'Content Type'}, { 'value': '© 2023 Published by Elsevier Ltd on behalf of International Society for ' 'Infectious Diseases.', 'name': 'copyright', 'label': 'Copyright'}]}
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop