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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality 42% Improvement Relative Risk Treatment escalation 6% Viral+ at day 7 15% HCQ for COVID-19  Lecronier et al.  ICU PATIENTS Is very late treatment with HCQ beneficial for COVID-19? Retrospective 80 patients in France Lower mortality with HCQ (not stat. sig., p=0.24) c19hcq.org Lecronier et al., Critical Care, 2020, Jul 2020 Favors HCQ Favors control

Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis

Lecronier et al., Critical Care, 24:418, 2020, doi:10.1186/s13054-020-03117-9
Jul 2020  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020
 
*, now known with p < 0.00000000001 from 422 studies, recognized in 42 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19hcq.org
Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences found for treatment escalation, ventilator-free days, viral load, or mortality. Authors consider treatment escalation more important than mortality, for unknown reasons.
This study is excluded in the after exclusion results of meta analysis: very late stage, >50% on oxygen/ventilation at baseline.
risk of death, 42.0% lower, RR 0.58, p = 0.24, treatment 9 of 38 (23.7%), control 9 of 22 (40.9%), NNT 5.8.
risk of treatment escalation, 6.0% lower, RR 0.94, p = 0.73, treatment 15 of 38 (39.5%), control 9 of 22 (40.9%), NNT 70.
risk of viral+ at day 7, 15.0% lower, RR 0.85, p = 0.61, treatment 19 of 26 (73.1%), control 12 of 14 (85.7%), NNT 7.9.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Lecronier et al., 11 Jul 2020, retrospective, France, peer-reviewed, baseline oxygen required 100.0%, 26 authors, HCQ vs. control.
This PaperHCQAll
Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
Marie Lecronier, Alexandra Beurton, Sonia Burrel, Luc Haudebourg, Robin Deleris, Julien Le Marec, Sara Virolle, Safaa Nemlaghi, Côme Bureau, Pierre Mora, Martin De Sarcus, Olivier Clovet, Baptiste Duceau, Paul Henri Grisot, Marie Hélène Pari, Jérémy Arzoine, Ulrich Clarac, David Boutolleau, Mathieu Raux, Julie Delemazure, Morgane Faure, Maxens Decavele, Elise Morawiec, Julien Mayaux, Alexandre Demoule, Martin Dres
Critical Care, doi:10.1186/s13054-020-03117-9
Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is spreading worldwide. To date, no specific treatment has convincingly demonstrated its efficacy. Hydroxychloroquine and lopinavir/ ritonavir have potential interest, but virological and clinical data are scarce, especially in critically ill patients. Methods: The present report took the opportunity of compassionate use and successive drug shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day 28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory tracts, and plasma viral load (as estimated by cycle threshold value) between admission and day 7.
Abbreviations ICU: Intensive care unit; SAPS II: Simplified Acute Physiology Score II; SOFA: Sequential Organ Failure Assessment; SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2; ECMO: Extra-corporeal membrane oxygenation; IQR: Interquartile range; CT: Cycle threshold; RT-PCR: Reverse transcription polymerase chain reaction Authors' contributions ML, LH, RD, and AB collected the patient's data. ML and MD analyzed the patient's data and have written the manuscript. All authors contributed to drafting the manuscript or critically revising it for important intellectual content and approved the final version of the manuscript. Funding None Ethics approval and consent to participate The Research Ethics Committee of Sorbonne University approved the project (CER 2020-36). Oral information about this retrospective analysis was given to patients or relatives. Consent for publication Not applicable Competing interests Martin Dres received fees from Lungpacer (expertise, lectures). A Demoule reports personal fees from Medtronic; grants, personal fees, and non-financial support from Philips; personal fees from Baxter; personal fees from Hamilton; personal fees and non-financial support from Fisher & Paykel; grants from French Ministry of Health; personal fees from Getinge; grants and personal fees from Respinor; and grants and non-financial support from Lungpacer, outside the submitted work. The other authors have no conflicts of interest to declare. Author..
References
Alhazzani, Møller, Arabi, Loeb, Gong, Surviving Sepsis Campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19), Intensive Care Med
Bhatraju, Ghassemieh, Nichols, Kim, Jerome et al., Covid-19 in critically ill patients in the Seattle region -case series, N Engl J Med
Cao, Wang, Wen, Liu, Wang et al., A trial of lopinavirritonavir in adults hospitalized with severe Covid-19, N Engl J Med
Chu, Cheng, Hung, Wong, Chan et al., Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings, Thorax
Corman, Landt, Kaiser, Molenkamp, Meijer et al., Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR, Euro Surveill
Cummings, Baldwin, Abrams, Sd, Meyer et al., Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study, Lancet
Gautret, Lagier, Parola, Hoang, Meddeb et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int J Antimicrob Agents
Geleris, Sun, Platt, Zucker, Baldwin et al., Observational study of hydroxychloroquine in hospitalized patients with Covid-19, N Engl J Med
Guan, Ni, Hu, Liang, Ou et al., Clinical characteristics of coronavirus disease 2019 in China, N Engl J Med
Horby, Landray, None
Keyaerts, Vijgen, Maes, Neyts, Van Ranst, In vitro inhibition of severe acute respiratory syndrome coronavirus by chloroquine, Biochem Biophys Res Commun
Nguyen, Dolladille, Drici, Fenioux, Alexandre et al., Cardiovascular toxicities associated with hydroxychloroquine and azithromycin: an analysis of the World Health Organization Pharmacovigilance Database
Romanelli, Smith, Hoven, Chloroquine and hydroxychloroquine as inhibitors of human immunodeficiency virus (HIV-1) activity, Curr Pharm Des
Roques, Thiberville, Dupuis-Maguiraga, Lum, Labadie et al., Paradoxical effect of chloroquine treatment in enhancing chikungunya virus infection, Viruses
Sanders, Monogue, Jodlowski, Cutrell, Pharmacologic treatments for coronavirus disease 2019 (COVID-19): a review, JAMA
Taccone, Gorham, Vincent, Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base, Lancet Respir Med
Touret, De Lamballerie, Of chloroquine and COVID-19, Antivir Res
Von Elm, Altman, Egger, Pocock, Gøtzsche et al., Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies, BMJ
Wang, Cao, Zhang, Yang, Liu et al., Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wang, Lu, Li, Chen, Chen et al., Clinical course and outcomes of 344 intensive care patients with COVID-19, Am J Respir Crit Care Med
Wu, Chen, Cai, Xia, Zhou et al., Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China, JAMA Intern Med
Yang, Yu, Xu, Shu, Xia et al., Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a singlecentered, retrospective, observational study, Lancet Respir Med
{ 'DOI': '10.1186/s13054-020-03117-9', 'ISSN': ['1364-8535'], 'URL': 'http://dx.doi.org/10.1186/s13054-020-03117-9', 'abstract': '<jats:title>Abstract</jats:title><jats:sec>\n' '<jats:title>Background</jats:title>\n' '<jats:p>The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak is ' 'spreading worldwide. To date, no specific treatment has convincingly demonstrated its ' 'efficacy. Hydroxychloroquine and lopinavir/ritonavir have potential interest, but virological ' 'and clinical data are scarce, especially in critically ill patients.</jats:p>\n' '</jats:sec><jats:sec>\n' '<jats:title>Methods</jats:title>\n' '<jats:p>The present report took the opportunity of compassionate use and successive drug ' 'shortages to compare the effects of two therapeutic options, lopinavir/ritonavir and ' 'hydroxychloroquine, as compared to standard of care only. The primary outcomes were treatment ' 'escalation (intubation, extra-corporeal membrane oxygenation support, or renal replacement ' 'therapy) after day 1 until day 28. Secondary outcomes included ventilator-free days at day ' '28, mortality at day 14 and day 28, treatment safety issues and changes in respiratory ' 'tracts, and plasma viral load (as estimated by cycle threshold value) between admission and ' 'day 7.</jats:p>\n' '</jats:sec><jats:sec>\n' '<jats:title>Results</jats:title>\n' '<jats:p>Eighty patients were treated during a 4-week period and included in the analysis: 22 ' '(28%) received standard of care only, 20 (25%) patients received lopinavir/ritonavir ' 'associated to standard of care, and 38 (47%) patients received hydroxychloroquine and ' 'standard of care. Baseline characteristics were well balanced between the 3 groups. Treatment ' 'escalation occurred in 9 (41%), 10 (50%), and 15 (39%) patients who received standard of care ' 'only, standard of care and lopinavir/ritonavir, and standard of care and hydroxychloroquine, ' 'respectively (<jats:italic>p</jats:italic>\u2009=\u20090.567). There was no significant ' 'difference between groups regarding the number of ventilator-free days at day 28 and ' 'mortality at day 14 and day 28. Finally, there was no significant change between groups in ' 'viral respiratory or plasma load between admission and day 7.</jats:p>\n' '</jats:sec><jats:sec>\n' '<jats:title>Conclusion</jats:title>\n' '<jats:p>In critically ill patients admitted for SARS-CoV-2-related pneumonia, no difference ' 'was found between hydroxychloroquine or lopinavir/ritonavir as compared to standard of care ' 'only on the proportion of patients who needed treatment escalation at day 28. Further ' 'randomized controlled trials are required to demonstrate whether these drugs may be useful in ' 'this context.</jats:p>\n' '</jats:sec>', 'alternative-id': ['3117'], 'article-number': '418', 'assertion': [ { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'Received', 'name': 'received', 'order': 1, 'value': '14 May 2020'}, { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'Accepted', 'name': 'accepted', 'order': 2, 'value': '29 June 2020'}, { 'group': {'label': 'Article History', 'name': 'ArticleHistory'}, 'label': 'First Online', 'name': 'first_online', 'order': 3, 'value': '11 July 2020'}, { 'group': {'label': 'Ethics approval and consent to participate', 'name': 'EthicsHeading'}, 'name': 'Ethics', 'order': 1, 'value': 'The Research Ethics Committee of Sorbonne University approved the project (CER ' '2020-36). 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N Engl J Med. 2020;382(21):2012–22.'}, { 'DOI': '10.1136/bmj.39335.541782.AD', 'author': 'E von Elm', 'doi-asserted-by': 'publisher', 'first-page': '806', 'journal-title': 'BMJ.', 'key': '3117_CR13', 'unstructured': 'von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, ' 'et al. Strengthening the Reporting of Observational Studies in ' 'Epidemiology (STROBE) statement: guidelines for reporting observational ' 'studies. BMJ. 2007;335:806–8.', 'volume': '335', 'year': '2007'}, { 'DOI': '10.2807/1560-7917.ES.2020.25.3.2000045', 'doi-asserted-by': 'crossref', 'key': '3117_CR14', 'unstructured': 'Corman VM, Landt O, Kaiser M, Molenkamp R, Meijer A, Chu DK, et al. ' 'Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR. ' 'Euro Surveill. 2020;25(3):2000045.'}, { 'DOI': '10.1016/j.antiviral.2020.104762', 'author': 'F Touret', 'doi-asserted-by': 'publisher', 'first-page': '104762', 'journal-title': 'Antivir Res', 'key': '3117_CR15', 'unstructured': 'Touret F, de Lamballerie X. Of chloroquine and COVID-19. Antivir Res. ' '2020;177:104762.', 'volume': '177', 'year': '2020'}, { 'DOI': '10.3390/v10050268', 'doi-asserted-by': 'crossref', 'key': '3117_CR16', 'unstructured': 'Roques P, Thiberville S-D, Dupuis-Maguiraga L, Lum F-M, Labadie K, ' 'Martinon F, et al. Paradoxical effect of chloroquine treatment in ' 'enhancing chikungunya virus infection. Viruses. 2018;10(5):268.'}, { 'DOI': '10.1016/S2213-2600(20)30172-7', 'doi-asserted-by': 'crossref', 'key': '3117_CR17', 'unstructured': 'Taccone FS, Gorham J, Vincent J-L. Hydroxychloroquine in the management ' 'of critically ill patients with COVID-19: the need for an evidence base. ' 'Lancet Respir Med. 20208(6):539–41.'}, { 'DOI': '10.1007/s00134-020-06022-5', 'author': 'W Alhazzani', 'doi-asserted-by': 'publisher', 'first-page': '854', 'journal-title': 'Intensive Care Med', 'key': '3117_CR18', 'unstructured': 'Alhazzani W, Møller MH, Arabi YM, Loeb M, Gong MN, Fan E, et al. ' 'Surviving Sepsis Campaign: guidelines on the management of critically ' 'ill adults with coronavirus disease 2019 (COVID-19). Intensive Care Med. ' '2020;46:854–87.', 'volume': '46', 'year': '2020'}, { 'DOI': '10.1164/rccm.202003-0736LE', 'author': 'Y Wang', 'doi-asserted-by': 'publisher', 'first-page': '1430', 'journal-title': 'Am J Respir Crit Care Med', 'key': '3117_CR19', 'unstructured': 'Wang Y, Lu X, Li Y, Chen H, Chen T, Su N, et al. Clinical course and ' 'outcomes of 344 intensive care patients with COVID-19. Am J Respir Crit ' 'Care Med. 2020;201:1430–4.', 'volume': '201', 'year': '2020'}, { 'DOI': '10.1016/S0140-6736(20)31189-2', 'doi-asserted-by': 'crossref', 'key': '3117_CR20', 'unstructured': 'Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ, Balough EM, et ' 'al. Epidemiology, clinical course, and outcomes of critically ill adults ' 'with COVID-19 in New York City: a prospective cohort study. Lancet. ' '2020;395(10239):1763–70.'}, { 'DOI': '10.1161/CIRCULATIONAHA.120.048238', 'doi-asserted-by': 'crossref', 'key': '3117_CR21', 'unstructured': 'Nguyen LS, Dolladille C, Drici M-D, Fenioux C, Alexandre J, Mira J-P, et ' 'al. Cardiovascular toxicities associated with hydroxychloroquine and ' 'azithromycin: an analysis of the World Health Organization ' 'Pharmacovigilance Database. Circulation. 2020. Online ahead of print.'}, { 'key': '3117_CR22', 'unstructured': 'Horby PW, Landray M. ' 'https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19; ' '2020.'}], 'reference-count': 22, 'references-count': 22, 'relation': {}, 'resource': {'primary': {'URL': 'https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03117-9'}}, 'score': 1, 'short-title': [], 'source': 'Crossref', 'subject': ['Critical Care and Intensive Care Medicine'], 'subtitle': [], 'title': 'Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill ' 'patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis', 'type': 'journal-article', 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'volume': '24'}
Late treatment
is less effective
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.
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