Authorization of issue in the Covid-19, already as a derogation, it is likely to be revised.
Disappointment for those who were expecting a profit of protocols based chloroquine or hydroxychloroquine (a derivative less toxic), at the early stage of Covid sufficiently disturbing to require hospitalization. A study published may 22 in the international scientific journal The Lancet, shows an excess of mortality among 15.000 patients have received, within 48 hours following the diagnosis, the chloroquine or hydroxychloroquine, associated or not with a macrolide family antibiotic which belongs to azithromycin, which is proposed in the protocol for the IHU Méditerranée infection).
The authors, led by the Pr Mandeep Mehra, of Harvard, remain cautious, since many of the protocols of prospective randomized studies, of superior quality to this observational study, are still in progress. “We have been unable to confirm a benefit of hydroxychloroquine or chloroquine, used alone or in dissociation with a macrolide, on the prognosis of patients Covid-19-hospitalized patients”, they write. “Each of these protocols, when it has been used for the treatment of Covid-19, has been linked to reduced survival in hospital and an increase in the occurrence of ventricular arrhythmias” (heart rhythm disorder is a severe, sometimes deadly, editor’s NOTE). The cardiotoxicity of these drugs is not a discovery: very early on, cardiologists and pharmacologists had warned about these adverse effects ; in France, the networks of pharmacovigilance had, between late march and late April, collected more than 100 reports of incidents of serious cv including four sudden, unexplained deaths, and five cardiac arrests that could be “recovered”.
To lead to this conclusion, the Pr Mehra and colleagues extracted data from 96 032 patients hospitalized for Covid confirmed by PCR, between the 20 December 2019, 14 April 2020, in 671 hospitals around the world. They have kept only those patients who had started such treatment in the 48 hours following the diagnosis. Among these, 14 888 received chloroquine (1868) or hydroxychloroquine (3016), possibly associated with a macrolide (with chloroquine for 3783 patients, or with hydroxychloroquine for 6221).
After statistical adjustments to ensure that the groups were reasonably comparable to the control group, it turns out that all these therapeutic diets increase mortality of hospitalized patients: chloroquine (x3,5), hydroxychloroquine (x2,3), choloroquine and macrolide (x4), hydroxychloroquine and a macrolide (x5). Of course, the authors remain cautious and refer to the randomized studies of good quality that are underway to conclude more firmly, even as they did not have an opinion on what is going on outside the hospital. They conclude, however: “Our analysis, large-scale international real-life, supports the absence of clinical benefit by chloroquine and hydroxychloroquine, and point to potential deleterious effects for patients hospitalized with Covid-19.”
The minister of health, Olivier Véran, governed immediately by a tweet. “Following the publication in The Lancet of a study alert on the ineffectiveness and risks of some treatments of the Covid-19 including hydroxychloroquine, I grabbed the HCSP (High Council of public health, editor’s NOTE) for the analysis and offers me within 48 hours to a revision of the overriding rules of limitation”, he wrote.
Because if the study still does not answer the question of the importance of treatment ultraprécoce, at the onset of symptoms, it could mark a halt to their use in patients hospitalized for Covid. The last time he had asked for the HCSP, the minister of Health did, in a first time, only partially followed his advice. The HCSP recommended in effect on march 23, of “book the treatment with hydroxychloroquine for severe forms of Covid-19, for hospital patients and to condition the implementation of this treatment to a collective decision”. Yet, Olivier Véran, by a decree signed two days later, there was neither a criterion of severity, or collegial decision! “By way of derogation from article L. 5121-8 of the code of public health, hydroxychloroquine, and lopinavir/ritonavir (antiviral drugs, editor’s NOTE) can be prescribed, dispensed and administered under the responsibility of a doctor to the patients by the Covid-19, in the health-care institutions that support them, as well as for the continuation of their treatment if their condition permits and the authorization of the prescriber’s initial at-home”, could we read in the decree of 25 march. The ministry, however, was income 24 hours later with the restrictions recommended by the HCSP: “The first paragraph is supplemented by the following sentence: “These requirements are involved, after a collegiate decision, in compliance with the recommendations of the High Council of public health and, in particular, the indication for patients with pneumonia oxygéno-applicant, or organ failure.””
That can now be added to the HCSP? Two main options open to him. The first would be to stick to current conditions, already sufficiently stringent, considering that the warning given by this new study, although not definitive, will be taken into account by the doctors. The second would be to allow the use of these molecules in the context of a clinical trial duly authorized. You can bet that, this time, the minister of Health will follow without hesitation the advice of the High Council.