Various medicines are being proposed to treat covid-19 infection by SARS-CoV-2. As of 23 March 2020, hydroxychloroquine (Plaquénil°), a derivative of chloroquine (Nivaquine°, an antimalarial), which also has a weak immunosuppressive effect, and azithromycin (Zithromax° or other brands), a macrolide, have been put forward. Interest has also been expressed in the antiretroviral combination lopinavir + ritonavir (Kaletra° or other brands), because of its antiviral action against coronaviruses in vitro.

As for chloroquine and its derivative hydroxychloroquine, around 20 clinical trials have been recorded in clinical trial registries since early February 2020, especially in China. As of 23 March 2020, no results of any randomised controlled trials have been published.

The results of a French study begun on 5 March 2020 were made public on 20 March 2020. The main objective was to study the carrying of the virus by patients treated with hydroxychloroquine. This study was not a randomised controlled trial, and the patients in the control group seem to have been selected very differently from the way the hydroxychloroquine group was selected, so any comparisons are not meaningful.

Amongst the 26 patients who received hydroxychloroquine, 3 patients were transferred to intensive care; one patient died. Two other patients decided to end their participation in the study. No such developments were recorded amongst the 16 patients in the control group. In the group treated with hydroxychloroquine, amongst the 18 patients for whom the date of onset of symptoms is known, the median time before non-detection of the virus was 7.5 days, with a wide confidence interval. In the absence of a control group selected according to a similar protocol and followed in the same conditions, it is not known whether this time is shorter than without hydroxychloroquine, or not.

In this study, in the 6 patients who took azithromycin in addition to hydroxychloroquine, this median time was 7 days. As of 23 March 2020, no other data from trials supporting the use of azithromycin in patients infected with covid-19 have been published.

The results of a randomised trial of the lopinavir + ritonavir combination, in addition to standard treatment, versus standard treatment alone, in 199 patients hospitalised with severe covid-19 infection were published on 18 March 2020. The rates of clinical improvement and of mortality in the 2 groups were similar.

The results of randomised comparative trials already carried out in China, as well as those that are getting underway in Europe and in South Korea, should allow for a clearer view of the situation.

Whatever the situation may be, when experiments are being carried out, patients (or their families) must be informed of the uncertainties, including the risk that the illness may be made worse, as long as this aspect has not yet been evaluated. Any experiments should take place in the context of a study, with a protocol, data collection, and prudent interpretation of results.

In practice, for each patient, the hypothetical efficacy must be weighed against the already known or predictable adverse effects of the treatment being proposed, also taking into account a possible worsening of the infection. Without losing sight of interactions with other medicines the patient is taking.

©Prescrire 23 March 2020

See also:

• "Covid-19 and hydroxychloroquine: caution" (30 March 2020) > HERE

Source:

"Covid-19 et essais de médicaments : que faire des premiers résultats d'évaluation ?" Application Prescrire; 23 March 2020.

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

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