The authorization to issue in Covid-19, which is already derogatory, is likely to be revised.
Disappointment for those who expected to benefit from chloroquine or hydroxychloroquine (a less toxic derivative) protocol, at the early stage of Covid sufficiently disturbing to require hospitalization. A study published on May 22 in the international scientific journal The Lancet shows an excess of mortality among 15,000 patients who received, within 48 hours of diagnosis, chloroquine or hydroxychloroquine, associated or not with a macrolide (family of antibiotic to which azithromycin belongs, proposed in the protocol of the IHU Mediterranean infection).
The authors, led by Pr Mandeep Mehra of Harvard remains cautious because many prospective randomized study protocols, therefore of superior quality to this observational study, are still in progress. “We were unable to confirm a benefit of hydroxychloroquine or chloroquine, used alone or in dissociation with a macrolide, on the prognosis of hospitalized Covid-19 patients”, they write. “Each of these protocols, when used for the treatment of Covid-19, has been associated with a decrease in hospital survival and an increase in the occurrence of ventricular arrhythmias” (serious heart rhythm disorder, sometimes fatal, note). The cardiotoxicity of these drugs is not a discovery: very early, cardiologists and pharmacologists had alerted on these undesirable effects; in France, the pharmacovigilance networks had, between the end of March and the end of April, collected more than 100 reports of serious cardiovascular incidents including four sudden and unexplained deaths and five cardiac arrests which could have been “recovered”.
To reach this conclusion, the Pr Mehra and colleagues extracted computer data from 96,032 patients hospitalized for Covid confirmed by PCR test, between December 20, 2019 and April 14, 2020, in 671 hospitals worldwide. They only kept patients who had started such treatment within 48 hours of diagnosis. Of these, 14,888 were receiving chloroquine (1,868) or hydroxychloroquine (3,016), possibly combined with a macrolide (with chloroquine for 3,783 patients, or with hydroxychloroquine for 6,221).
Statistical adjustments
After statistical adjustments to ensure that the groups were reasonably comparable to the control group, it turns out that all these therapeutic regimes increase the mortality of hospitalized patients: chloroquine (x3.5), hydroxychloroquine (x2.3), choloroquine and macrolide (x4), hydroxychloroquine and macrolide (x5). Obviously, the authors remain cautious and refer to the good quality randomized studies that are underway to conclude more firmly, just as they do not comment on what is going on outside the hospital. They nevertheless conclude: “Our large-scale, real-world analysis supports the lack of clinical benefit from chloroquine and hydroxychloroquine and points to potential deleterious effects for patients hospitalized with Covid-19.”
The Minister of Health, Olivier Véran, immediately governed by a tweet. “Following the publication in The Lancet of a study alerting to the ineffectiveness and risks of certain treatments of Covid-19 including hydroxychloroquine, I asked the HCSP (High Council of Public Health, Editor’s note) so that he can analyze it and suggest to me within 48 hours a review of the derogating prescription rules “, he wrote.
Because if the study still does not answer the question of the interest of an ultra-early treatment, as of the appearance of the symptoms, it could mark a stop of their use in patients hospitalized for Covid. The last time he asked the HCSP, the Minister of Health initially only partially followed his advice. The HCSP recommended in effect on March 23 “Reserve treatment with hydroxychloroquine for severe forms of Covid-19, for hospitalized patients and make the implementation of this treatment conditional on a collegial decision”. However, Olivier Véran, by a decree signed two days later, imposed neither seriousness criteria nor collegial decisions! “By derogation from article L. 5121-8 of the public health code, hydroxychloroquine and the combination lopinavir / ritonavir (antivirals, note) may be prescribed, dispensed and administered under the responsibility of a doctor to patients affected by Covid-19, in the healthcare establishments which take care of them, as well as for the continuation of their treatment if their condition allows it and on authorization of the initial prescriber, at home “, could we read in the decree of March 25. The ministry, however, returned 24 hours later to the restrictions recommended by the HCSP: “The first paragraph is supplemented by the following sentence:” These prescriptions come into play, after collegial decision, in compliance with the recommendations of the High Council of Public Health and, in particular, the indication for patients with oxygen-requiring pneumonia or organ failure. ””
What can the HCSP now add? There are two main options available to him. The first would be to stick to the current conditions, already sufficiently strict, considering that the alert given by this new study, although not definitive, will be taken into account by the doctors. The second would be to authorize the use of these molecules only within the framework of a duly authorized clinical trial. We bet that this time the Minister of Health will follow the advice of the High Council without hesitation.
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