Update Alert 2: Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points From the American College of Physicians
Authors: Amir Qaseem, Jennifer Yost, Itziar Etxeandia-Ikobaltzeta, Linda L. Humphrey
Journal: Annals of Internal Medicine (2020)

Letters30 July 2020Update Alert 2: Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points From the American College of PhysiciansFREEAmir Qaseem, MD, PhD, MHA, Jennifer Yost, RN, PhD, Itziar Etxeandia-Ikobaltzeta, PharmD, PhD, and Linda L. Humphrey, MD, MPHAmir Qaseem, MD, PhD, MHAAmerican College of Physicians, Philadelphia, Pennsylvania (A.Q.)Search for more papers by this author, Jennifer Yost, RN, PhDVillanova University, Villanova, Pennsylvania (J.Y.)Search for more papers by this author, Itziar Etxeandia-Ikobaltzeta, PharmD, PhDHospital Santa Margarita Trasera, Irun, Spain (I.E.)Search for more papers by this author, and Linda L. Humphrey, MD, MPHOregon Health & Science University, Portland, Oregon (L.L.H.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-1007 SectionsAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This letter serves to retire the American College of Physicians' (ACP) rapid, living practice points on the use of chloroquine or hydroxychloroquine alone or in combination with azithromycin for the prophylaxis or treatment of coronavirus disease 2019 (COVID-19) (1, 2) from the living status. This decision was made in light of recent information on the topic. Three large, in-progress randomized controlled trials (RCTs) with strong study designs ceased enrollment for the hydroxychloroquine-only versus control comparison early due to lack of efficacy in preliminary analyses (3–5). In addition, the 2 literature updates produced no evidence to alter these conclusions. The U.S. Food and Drug Administration also recently revoked its emergency use authorization for chloroquine and hydroxychloroquine for the treatment of COVID-19 due to potential significant harms and lack of benefits (6). The ACP's Scientific Medical Policy Committee (SMPC) has determined that the emergence of new evidence is unlikely to change the existing practice points; therefore, regularly scheduled updates are no longer warranted. The SMPC will continue to review the planned ongoing surveillance through November 2020 (7). The updated evidence review (8) identified 1 new RCT (9); 5 new cohort studies (10–14); and complete published reports of studies previously available as preprints, which resulted in changes in rating of the risk of bias (15, 16). A sixth newly published large cohort study was identified but not considered further because it was retracted due to concerns about the veracity of the data (17, 18). The newly available evidence has high risk of bias and showed conflicting direction and magnitude of results, leading to unchanged conclusions from the initial review with insufficient evidence to support the effectiveness or safety of chloroquine or hydroxychloroquine alone or in combination with azithromycin for the treatment of COVID-19 in hospitalized patients. Furthermore, 3 RCTs were stopped early (3–5) and no data were available to assess from those RCTs.Practice PointsDo not use chloroquine or hydroxychloroquine alone or in combination with azithromycin as prophylaxis against COVID-19.Do not use chloroquine or hydroxychloroquine alone or in combination with azithromycin as a treatment of patients with COVID-19.Clinicians may choose to treat hospitalized COVID-19–positive patients with chloroquine or hydroxychloroquine alone or in combination with azithromycin in the context of a clinical trial, using shared and informed decision making with patients (and their families).References1. Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al. Should clinicians use chloroquine or hydroxychloroquine alone or in combination with azithromycin for the prophylaxis or treatment of COVID-19? Living practice points from the American College of Physicians (version 1). Ann Intern Med. 2020;173:137-142. [PMID: 32422063]. doi:10.7326/M20-1998 LinkGoogle Scholar2. Qaseem A, Yost J, Etxeandia-Ikobaltzeta I, et al. Update alert: should clinicians use chloroquine or hydroxychloroquine alone or in combination with azithromycin for the prophylaxis or treatment of COVID-19? Living practice points from the American College of Physicians [Letter]. Ann Intern Med. 2020;173:W48-W51. [PMID: 32551892]. doi:10.7326/M20-3862 LinkGoogle Scholar3. RECOVERY trial. No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19: statement from the chief investigators of the randomised evaluation of covid-19 therapy (RECOVERY) trial on hydroxychloroquine. 5 June 2020. Accessed at 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 on 6 July 2020. Google Scholar4. World Health Organization. WHO discontinues hydroxychloroquine and lopinavir/ritonavir treatment arms for COVID-19 [news release]. 4 July 2020. Accessed at www.who.int/news-room/detail/04-07-2020-who-discontinues-hydroxychloroquine-and-lopinavir-ritonavir-treatment-arms-for-covid-19 on 6 July 2020. Google Scholar5. National Institutes of Health. NIH halts clinical trial of hydroxychloroquine: study shows treatment does no harm, but provides no benefit [news release]. 20 June 2020. Accessed at www.nih.gov/news-events/news-releases/nih-halts-clinical-trial-hydroxychloroquine on 6 July 2020. Google Scholar6. U.S. Food and Drug Administration. Coronavirus (COVID-19) update: FDA revokes emergency use authorization for chloroquine and hydroxychloroquine [news release]. 15 June 2020. Accessed at www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-revokes-emergency-use-authorization-chloroquine-and on 16 July 2020. Google Scholar7. Hernandez AV, Roman YM, Pasupuleti V, et al. Hydroxychloroquine or chloroquine for treatment or prophylaxis of COVID-19: a living systematic review. Ann Intern Med. 2020. [PMID: 32459529]. doi:10.7326/M20-2496 LinkGoogle Scholar8. Hernandez AV, Roman YM, Pasupuleti V, et al. Update alert: hydroxychloroquine or chloroquine for the treatment or prophylaxis of COVID-19 [Letter]. Ann Intern Med. 2020. [PMID: 32667853]. doi:10.7326/L20-0945 LinkGoogle Scholar9. Chen L, Zhang ZY, Fu JG, et al. Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study. medRxiv. Preprint posted online 22 June 2020. doi:10.1101/2020.06.19.20136093 Google Scholar10. Sbidian E, Josse J, Lemaitre G, et al. Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France. medRxiv. Preprint posted online 19 June 2020. doi:10.1101/2020.06.16.20132597 Google Scholar11. Rosenberg ES, Dufort EM, Udo T, et al. Association of treatment with hydroxychloroquine or azithromycin with in-hospital mortality in patients with COVID-19 in New York State. JAMA. 2020. [PMID: 32392282] doi:10.1001/jama.2020.8630 CrossrefMedlineGoogle Scholar12. Ip A, Berry DA, Hansen E, et al. Hydroxychloroquine and tocilizumab therapy in COVID-19 patients—an observational study. medRxiv. Preprint posted online 25 May 2020. doi:10.1101/2020.05.21.20109207 Google Scholar13. Singh S, Khan A, Chowdhry M, et al. Outcomes of hydroxychloroquine treatment among hospitalized COVID-19 patients in the United States—real-world evidence from a federated electronic medical record network. medRxiv. Preprint posted online 19 May 2020. doi:10.1101/2020.05.12.20099028 Google Scholar14. Arshad S, Kilgore P, Chaudhry ZS, et al; Henry Ford COVID-19 Task Force. Treatment with hydroxychloroquine, azithromycin, and combination in patients hospitalized with COVID-19. Int J Infect Dis. 2020;97:396-403. [PMID: 32623082] doi:10.1016/j.ijid.2020.06.099 CrossrefMedlineGoogle Scholar15. Tang W, Cao Z, Han M, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849. [PMID: 32409561] doi:10.1136/bmj.m1849 CrossrefMedlineGoogle Scholar16. Yu B, Li C, Chen P, et al. Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19. Sci China Life Sci. 2020. [PMID: 32418114] doi:10.1007/s11427-020-1732-2 CrossrefMedlineGoogle Scholar17. Rosenthal M. 2 papers about drug therapy for COVID-19 retracted from prestigious journals. Pharmacy Practice News. 4 June 2020. Accessed at www.pharmacypracticenews.com/Covid-19/Article/05-20/2-Papers-AboutDrug-Therapy-in-COVID-19-Retracted-From-Prestigious-Journals/58677 on 6 July 2020. Google Scholar18. Mehra MR, Desai SS, Ruschitzka F, et al. RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis. Lancet. 2020. [PMID: 32450107] doi:10.1016/S0140-6736(20)31180-6 CrossrefMedlineGoogle Scholar Comments 0 Comments Sign In to Submit A Comment Joe Roosth MDPrivate Practice31 July 2020 If only If only this could be promoted as fact by certain National News organizations Disclosures: None Mark Scapini-31 July 2020 Hydroxychloroquine use The data regarding hydroxychloroquine by your admission is conflicting. It is so disappointing that the ACP has joined the politicization of a safe and potentially beneficial drug. Disclosures: None Dr. James W. DunnavantPrivate practice.3 August 2020 Zinc is vital. Zinc is vital to be used in conjunction with HQC and Zpac. The study IMO was designed to fail. Zinc is vital to disrupt replication. This article may have an impact on membership rolls. Disclosures: None Vinu ArumughamIndependent3 August 2020 HCQ evaluation is among the most deadly frauds/crimes in the history of medicine When appropriately dosed and appropriately timed, HCQ works. RECOVERY and SOLIDARITY used OVERDOSES to KILL patients. Then they declared HCQ is dangerous. Criminal charges need to be filed here. Then there were the outright fabrications retracted by THE LANCET and the NEJM. Now you use these horrible sources to deny HCQ and kill even more patients. Many third world countries are using appropriate HCQ doses to save lives as well as for prophylaxis. "Hydroxychloroquine was dosed as 400 mg twice daily for 2 doses on day 1, followed by 200 mg twice daily on days 2–5." https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext It worked in this case because it was appropriately dosed. Canadian and Norwegian Solidarity are using overdoses. "Hydroxychloroquine 800mg BID for 1 day then 400mg BID for 10 days" https://clinicaltrials.gov/ct2/show/NCT04330690 "Hydroxychloroquine will be given orally (in the ICU in gastrointestinal tubes) with 800 mg x 2 loading dose followed by 400 mg x 2 every day for a total of 10 days." https://clinicaltrials.gov/ct2/show/NCT04321616 https://www.ageofautism.com/2020/06/who-solidarity-and-uk-recovery-clinical-trials-of-hydroxychloroquine-using-potentially-fatal-doses.html Disclosures: This author has nothing to disclose. Premila LevaciPrincipal Medical Scientist – Clinical R&D Collaborations - BioSci Rx Trials Australia3 August 2020 Update Alert 2: Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points From the American College of Physicians. The evidence to support the continued use of hydroxychloroquine for SARS CoV2 in patients with CoVID19 infection is not supported by some large clinical trials: https://www.nejm.org/doi/full/10.1056/NEJMoa2019014?query=TOC. This article was published on July 23, 2020, at NEJM.org. for the Coalition Covid-19 Brazil I Investigators. Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19. A multicentre, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19. A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. Conclusions: Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, opens in new tab.). (2) Kai Kupferschmidt - Science 10 Jul 2020: Vol. 369, Issue 6500, pp. 124-125. CoVID19 ‘Megatrial in UK outshines other trials’. DOI: 10.1126/science.369.6500.124 - University of Oxford clinical scientists Martin Landray and Peter Horby And the Recovery Trial Investigators. https://science.sciencemag.org/content/369/6500/124?utm_campaign=toc_sci-mag_2020-07-09&et_rid=33953473&et_cid=3401489 Disclosure of Any Conflicts of Interest (optional): None Author, Article, and Disclosure InformationAuthors: Amir Qaseem, MD, PhD, MHA; Jennifer Yost, RN, PhD; Itziar Etxeandia-Ikobaltzeta, PharmD, PhD; Linda L. Humphrey, MD, MPHAffiliations: American College of Physicians, Philadelphia, Pennsylvania (A.Q.)Villanova University, Villanova, Pennsylvania (J.Y.)Hospital Santa Margarita Trasera, Irun, Spain (I.E.)Oregon Health & Science University, Portland, Oregon (L.L.H.)Note: The Practice Points are developed by the Scientific Medical Policy Committee of the American College of Physicians. The Practice Points are “guides” only and may not apply to all patients and all clinical situations. All Practice Points are considered automatically withdrawn or invalid 5 years after publication or once an update has been issued.Financial Support: Financial support for the development of the Practice Points comes exclusively from the ACP operating budget.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-1007. All financial and intellectual disclosures of interest were declared, and potential conflicts were discussed and managed. A record of disclosures of interest and management of conflicts is kept for each Scientific Medical Policy Committee meeting and conference call and can be viewed at https://www.acponline.org/about-acp/who-we-are/leadership/boards-committees-councils/scientific-medical-policy-committee/disclosure-of-interests-and-conflict-of-interest-management-summary-for-scientific-medical-policy.Corresponding Author: Amir Qaseem, MD, PhD, MHA, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106; e-mail, aqaseem@acponline.org.This article was published at Annals.org on 30 July 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoShould Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points From the American College of Physicians (Version 1) Amir Qaseem , Jennifer Yost , Itziar Etxeandia-Ikobaltzeta , Matthew C. Miller , George M. Abraham , Adam Jacob Obley , Mary Ann Forciea , Janet A. Jokela , and Linda L. Humphrey , for the Scientific Medical Policy Committee of the American College of Physicians*Update Alert: Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for the Prophylaxis or Treatment of COVID-19? Living Practice Points From the American College of Physicians Amir Qaseem , Jennifer Yost , Itziar Etxeandia-Ikobaltzeta , Matthew C. Miller , George M. Abraham , Adam J. Obley , Mary Ann Forciea , Janet A. Jokela , and Linda L. Humphrey , for the Scientific Medical Policy Committee of the American College of Physicians* Metrics Cited byThe Rush to Publish Research on the PandemicImpact of Treatment Regimens on Antibody Response to the SARS-CoV-2 CoronavirusLet’s do better: public representations of COVID-19 scienceNational Psoriasis Foundation COVID-19 Task Force Guidance for Management of Psoriatic Disease During the Pandemic: Version 1Hydroxychloroquine for prophylaxis of COVID ‐19 physicians survey: Despite lack of evidence, many would take or give to dear ones, and despite the perceived necessity of an RCT , few would participate 1 September 2020Volume 173, Issue 5 Page: W88-W89 Keywords Chloroquine Cohort studies COVID-19 Disclosure Hydroxychloroquine Patients Prophylaxis Risk management Safety ePublished: 30 July 2020 Issue Published: 1 September 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...