Results of a Chinese comparative trial of hydroxychloroquine (Plaquenil°) were published online at the end of March 2020, before peer review (> here). This trial compared standard treatment of covid-19 versus addition of hydroxychloroquine. The described protocol differed from that recorded in the Chinese clinical trial registry.

This trial was conducted in 62 patients with covid-19 (mean age about 45 years) with signs of pneumonia, but no significant change in oxygen saturation. During a 6-day follow-up, 4 patients developed a severe form of covid-19 in the control group (standard treatment) versus none in the group with addition of hydroxychloroquine (400 mg per day for 5 days) (difference not statistically significant).  Radiological imaging (chest CT) also appeared to show a better outcome in the hydroxychloroquine group.

Questions remain, however:

• Did any patients die during the course of the trial?
• Was the length of follow-up sufficient to assess mortality, given the usual duration of the disease?
• Was the length of follow-up sufficient to assess the harmful effects of the treatment, given that the elimination half-life of hydroxychloroquine varies from a few days to 2 months, resulting for example in prolonged exposure to drug interactions which may contribute to electrocardiographic QT interval prolongation?

On the other hand, a French team reported results (> here) on a series of patients treated with hydroxychloroquine (600 mg per day) and azithromycin (500 mg on the first day, then 250 mg per day for 4 days). After 5 to 6 days of treatment, nasopharyngeal samples were still positive for SARS-CoV-2 by PCR testing in 8 out of 10 patients studied. In one patient, the treatment was stopped on the fourth day due to QT interval prolongation.

The uncertainty remaining after these results, added to those of a previous trial ("Covid-19 and hydroxychloroquine: caution" > here), means that comparative evaluations must be continued, and that great care should still be taken in the use of hydroxychloroquine, given its cardiac and other harms.

©Prescrire 2 April 2020

See also:

• "Covid-19 and drug trials: what to make of the initial results?" (23 March 2020) > HERE
  
• "Covid-19 and hydroxychloroquine: caution" (30 March 2020) > HERE
  

Source:

"Covid-19 et hydroxychloroquine : incertitudes et questions qui se posent" Application Prescrire; 2 April 2020.

For more information (in French), see www.prescrire.org > Dans l'actualité

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