Chloroquine continues to be talked about and just recently two new studies have been conducted. The results are similar: no beneficial effect on patients with coronavirus has been observed.
[Mis à jour le 15 mai 2020 à 16h32] Having become a national debate, chloroquine continues to benefit from very intense media coverage and especially studies of all kinds, while its usefulness in the treatment against coronavirus has never been ruled out or confirmed. Recently, we learned about the results of two studies on the subject, one of which was conducted in France. The latter, which rather concerns subjects with severe symptoms, has shown that the molecule traditionally used to treat malaria does not significantly reduce the number of patients entering intensive care and deaths linked to the coronavirus. The second study, done in China, is more telling for mild or moderate Covid-19 patients and the conclusions are similar: hydroxychloroquine would not have better effects than standard treatment.
Chloroquine is a molecule used in medicine in antimalarial treatments. In other words, it is used as a preventative before going to countries at risk, as in curative once malaria is contracted. Hydroxychloroquine is the most commonly administered substance by mouth. Chloroquine then has a hydroxyl group (the OH entity comprising a bonded oxygen and hydrogen atom). We speak most often of “hydroxychloroquine sulfate”.
Nivaquine and Plaquenil are the other terms often used in connection with potential treatment for coronavirus. These are actually the names behind which the molecules of chloroquine and hydroxychloroquine are marketed. Nivaquine is a brand of Sanofi that presents chloroquine in the form of a 100 mg scored tablet. Plaquenil, from the same pharmaceutical group, is composed of hydroxychloroquine sulfate in the form of 200 mg tablets. Chloroquine or hydroxychloroquine are also found under the brands Axemal, Dolquine and Quensyl. All these treatments are also used in the treatment of rheumatoid arthritis and lupus. In France, the only French manufacturer of chloroquine (Sanofi – NDLR) is currently working to supply the establishments carrying out tests.
The media and public opinion began to take an interest in chloroquine when, in mid-March, Professor Didier Raoult presented the results of a study, considered to be encouraging. This specialist in emerging tropical diseases, known to take certain liberties with protocols for use in scientific demonstration, had tested on 24 patients a treatment consisting of hydroxychloroquine and azithromycin (an antibiotic). After the tests, 75% were no longer carrying Covid-19. This study was immediately subject to controversy for the small sample of patients tested and for the absence of a control group (group of patients to whom the treatment studied is not administered but a placebo generally, to clearly observe the difference in the evolution of the disease): two parameters considered essential to judge the scientific validation of a result.
The conclusions of a second study on the effect of chloroquine were revealed by Didier Raoult on Saturday March 28. 80 patients were tested this time, which was close to some traditional clinical trials. The median age of the patients was 52 years, 58% presented a comorbidity (hypertension, diabetes, chronic respiratory disease…). For 6-10 days, the patients were again given a combination of hydroxychloroquine (3 x 200 mg daily) and azithromycin. At the end of the study, 81% experienced a favorable development and were discharged from the hospital quickly (after 4.6 days). 13 patients were still in intensive care after 10 days and one subject died. In 93% of subjects, the viral load was undetectable after eight days. The microbiologist delivered this conclusion: “We confirm the efficacy of hydroxychloroquine associated with azithromycin in the treatment of Covid-19.” Again, this study was highly criticized for the absence of control groups: it should indeed be remembered that a large majority of people who contracted the coronavirus recover without any specific treatment, which makes it difficult to analyze the figures of Pr Raoult.
Pr Raoult’s third experiment, in early April, involved 1,061 Covid + patients. The median age was 43.8 years, 46.4% were men and no cardiac toxicity was observed. All received treatment with hydroxychloroquine and azithromycin. Within ten days, virological healing was observed in 91.7% of patients. Five elderly patients died, ten were placed in intensive care and 31 were hospitalized for ten days or more. According to the IHU, the study has shown that when treatment is administered early, it is “safe and effective against Covid-19, with a mortality rate of 0.5% in older patients. aggravation and eliminates the persistence and contagiousness of the virus in most cases. “
“At very high doses, chloroquine can kill”, bluntly alerted on March 30 in Le Parisien, Professor François Bricaire, member of the Academy of Medicine. Le Monde reported that since March 27, 54 cases of cardiac disorders – including seven fatal – have been identified at the regional pharmacovigilance center (CRPV) in Nice, responsible for the national surveillance of cardiac adverse effects of the drugs evaluated in the infection to the new coronavirus. Taking hydroxychloroquine alone or in combination with azithromycin is believed to be involved in nine of the deaths. Dominique Martin, the director general of the National Agency for the Safety of Medicines (ANSM), called for caution: “Pending the results of the numerous clinical trials in progress, it is legitimate to reserve the prescriptions of these products for the hospital environment “.
Overdosage of chloroquine can be very dangerous. The molecule is considered to be a drug with a narrow therapeutic margin, i.e. the difference between the effective dose and the toxic dose is small. The main symptoms of poisoning are: cardiovascular disorders, digestive disorders (nausea and vomiting) and neurosensory signs. According to the French Network of Regional Pharmacovigilance Centers, whatever the dose supposed to be ingested, any chloroquine poisoning requires prehospital care by a mobile emergency service.
Performing an ECG before and during treatment is strongly recommended. It can lead to cardiomyopathy, conduction and heart rhythm disorders (atrioventricular block, prolongation of the QTc interval, torsades de pointes, ventricular tachycardia, ventricular fibrillation). Other side effects may occur: gastrointestinal complaints, mucocutaneous effects (especially pruritus and rashes), hematological disorders, psychiatric disorders, nervous system disorders (headache, dizziness and convulsions), metabolic disorders, eye effects (exceptional cases of retinopathies linked to the accumulation of the molecule and which can lead to irreversible damage to the macula) and hepatobiliary disorders.
In addition, certain contraindications should be noted: in the event of allergy to chloroquine or hydroxychloroquine, retinopathy or certain drug interactions (in particular with citalopram or escitalopram, domperidone, hydroxyzine or piperaquine). Finally, the treatment requires precautions for use in diabetic, epileptic, cardiac subjects, suffering from Parkinson’s disease, suffering from porphyria or having disorders of serum potassium or magnesemia. The Network recommends that chloroquine and hydroxychloroquine be avoided during pregnancy “unless the clinical situation justifies the use of the treatment in view of the potential risks incurred for the mother and the fetus.”
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