COVID-19: Chloroquine and hydroxychloroquine research

What this guideline says

GMJ summary

This rapid systematic review, published on 6 April 2020, evaluates the available evidence for using chloroquine or hydroxychloroquine in the treatment of COVID-19. At the time of publication, there was a lack of quality evidence to demonstrate that chloroquine and/or hydroxychloroquine are effective in treating COVID-19. The evidence was emerging from small studies with sub-optimal methodologies that were conflicting and at high risk of bias.

The review emphasizes that while in vitro studies showed some antiviral activity, the in vivo human studies were methodologically weak, with small sample sizes, lack of proper randomization, inadequate blinding, and poor reporting. National authorities are urged to control the use of these medicines, prevent self-medication, and prioritize resources on standard-of-care interventions. The use of these drugs outside current guidelines may result in adverse effects, including serious illness and death, particularly cardiac complications such as QT-interval prolongation and potentially lethal arrhythmias.

PAHO emphasizes that robust, high-quality randomized controlled trials are urgently needed before any definitive conclusions can be drawn about benefits and harms. The organization commits to updating recommendations as new evidence from ongoing clinical trials becomes available. Until definitive evidence is available, compassionate use should be approached with extreme caution, particularly given concerns about cardiac toxicity and drug shortages affecting patients with rheumatoid arthritis, lupus, and other conditions where these drugs have proven benefit.

Key points

For clinicians — doses and thresholds as stated in the guideline

1. No quality evidence exists as of 6 April 2020 to demonstrate chloroquine or hydroxychloroquine effectiveness in COVID-19 treatment
2. One Chinese expert consensus suggested chloroquine phosphate 500 mg twice daily for 10 days, but this is based on very limited and unpublished data
3. A French study used hydroxychloroquine 600 mg daily for 10 days, sometimes with azithromycin (500 mg day 1, then 250 mg daily for 4 days), but was judged at high risk of bias
4. Cardiac toxicity is a major concern: hydroxychloroquine/azithromycin can prolong QT interval and cause torsade de pointes, a potentially lethal ventricular tachycardia
5. In one series of 84 COVID-19 patients treated with hydroxychloroquine/azithromycin, 11% developed QTc >500 ms (high arrhythmia risk)
6. National authorities should control availability of these medicines and prevent self-medication, as over-the-counter use may cause serious adverse effects including death
7. Priority should be given to standard supportive care interventions; use of chloroquine/hydroxychloroquine should be restricted to ethically approved randomized controlled trials
8. Mass purchasing may create shortages affecting patients with malaria, rheumatoid arthritis, lupus, and other conditions where these drugs have proven benefit

Risk of bias assessment for observational studies on hydroxychloroquine/azithromycin in COVID-19

Table extracted from the guideline

Source: Pan American Health Organization, COVID-19: Chloroquine and hydroxychloroquine research. Reproduced in summary form.

From the guideline

Verbatim

“As of the date of this document, there is a lack of quality evidence to demonstrate chloroquine and/or hydroxychloroquine are effective in the treatment of COVID-19.”

Editor’s perspective

Why this matters for Georgia and the region

Applicability

Georgia and the South Caucasus

Questions this guideline answers

Quick answers

Related on GMJ

Interconnected resources

GMJ Guidelines Library records are original summaries written by the GMJ editorial team from the issuer’s published document and reviewed by a physician. They do not replace the full guideline. The document is the copyright of its issuer and is linked, not hosted. Spotted an error or a newer edition? Tell the Guidelines Desk.