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).

Key Question 1

Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for Prophylaxis Against COVID-19?

Key Question 2

Should Clinicians Use Chloroquine or Hydroxychloroquine Alone or in Combination With Azithromycin for Treatment of COVID-19?

Background

Using chloroquine or hydroxychloroquine, with or without azithromycin, to prevent coronavirus disease (COVID-19) after infection with novel coronavirus (SARS-CoV-2) or to treat COVID-19 began to receive attention following preliminary reports from in vitro (1) and human (2) studies. While multiple studies are planned or under way (3, 4), it is imperative to continually synthesize the results from the best available evidence to inform point-of-care decisions about the use of chloroquine or hydroxychloroquine. These practice points are based on a rapid and living systematic evidence review conducted by the University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group and will be updated as new evidence becomes available. The practice points development and update methods are included in the Appendix, available at Annals.org. This version of the practice points, based on an evidence review conducted on 17 April 2020, was approved by the American College of Physicians Board of Regents on 4 May 2020 and submitted to Annals of Internal Medicine on 6 May 2020.

Practice Points

The efficacy of chloroquine or hydroxychloroquine alone or in combination with azithromycin to prevent COVID-19 after infection with SARS-CoV-2 or to treat patients with COVID-19 is not established and future clinical trials are needed to answer these questions. There are known harms of these medications when used to treat other diseases (5, 6). Current evidence about efficacy and harms for use in the context of COVID-19 is sparse, conflicting, and from low quality studies, increasing the uncertainty and lowering our confidence in the conclusions of these studies when assessing the benefits or understanding the balance when compared with harms. These interim practice points are based on best available evidence. We will maintain these practice points as a living guidance document, updated as new evidence becomes available.

• Do not use chloroquine or hydroxychloroquine alone or in combination with azithromycin as prophylaxis against COVID-19 due to known harms and no available evidence of benefits in the general population.

• Do not use chloroquine or hydroxychloroquine alone or in combination with azithromycin as a treatment of patients with COVID-19 due to known harms and no available evidence of benefits in patients with COVID-19.

• In light of known harms and very uncertain evidence of benefit in patients with COVID-19, using shared and informed decision making with patients (and their families), clinicians may treat hospitalized COVID-19–positive patients with chloroquine or hydroxychloroquine alone or in combination with azithromycin in the context of a clinical trial.

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Evidence Description for COVID-19 Studies*.

COVID-19 = coronavirus disease 2019; RCT = randomized controlled trial.

* Evidence search was conducted by the University of Connecticut Health Outcomes, Policy, and Evidence Synthesis Group. Current search for evidence, completed on 17 April 2020, aimed to identify all studies about the use of chloroquine or hydroxychloroquine alone or in combination for prophylaxis or treatment of patients with COVID-19. (See Supplement, available at Annals.org.)

† The use and extent of parallel treatment interventions was difficult to determine. For example, in some studies, it was documented that patients received parallel interventions, whereas in other studies there was insufficient information to determine if patients did or did not receive parallel interventions.

‡ In 2 cohort studies (11, 12), the administration of azithromycin was not randomized, precluding judgment of efficacy

Should chloroquine or hydroxychloroquine alone or in combination with azithromycin be used as prophylaxis against COVID-19 in the general population?

Should chloroquine or hydroxychloroquine alone or in combination with azithromycin be used for treatment of patients with COVID-19?

Evidence Summary: What Information Does the Evidence Provide?