COVID-19: HCQ fails in first randomised controlled trials in France, China

Both studies show significant adverse effects of the drug on moderate and serious patients

By Banjot Kaur
Published: Saturday 16 May 2020

Anti-malarial drug Hydorxychloroquine (HCQ) — claimed by many to show promise in combating the novel coronavirus disease (COVID-19) — failed in two separate randomised controlled trials (RCTs) conducted in France and China. The results of the RCTs were published in journal the BMJ on May 15, 2020.

A number of in-vitro (lab-based) and observational studies were already performed on the drug as a potential therapeutic against COVID-19. The in-vitro results were positive, but observational studies showed mixed results.

The first RCT on the drug — conducted in China — however, dampened any potential against COVID-19.

Chloroquine and HCQ were both recommended for off-label use by Chinese national guidelines and the US Food and Drug Administration, despite unclear benefits, according to the paper.

“US President Donald Trump also recently recommended use of HCQ. Such a presidential endorsement stimulated a rapid increase in demand for HCQ, which obscured its negative aspects,” the paper said.

The Indian Council of Medical Research (ICMR), in fact, also prescribed the drug as ‘prophylactic (preventive) treatment’ for healthcare workers, serious patients and contacts of confirmed cases.

Chinese Study

One hundred and fifty patients suffering from mild to moderate forms of COVID-19 were enrolled from the Chinese province of Hubei, Henan and Anhui for the study, which claimed it was the first RCT ever conducted for the evaluation of HCQ.

They were divided into two groups: One that received HCQ plus the normal standard of care and the other that received only care. Two-hundred milligrams (mg) of HCQ was given to the patients everyday for three days, followed by a maintenance dose of 800 mg daily for the remaining days.

The target was to see if there was a negative conversion of the SARS-CoV-2 virus (being free of the virus) in patients within 28 days. Out of 150 patients, 109 showed this result.

Of these, 53 received HCQ plus normal standard of care, while 56 received only care. “The probability of negative conversion by 28 days in the standard of care plus HCQ group was 85.4 per cent, similar to that in the standard of care group that is, 81.3 per cent,” the study pointed out.

“The difference between groups was 4.1 per cent,” the study added, showing there was no significant achievement due to HCQ in the patients.

The drug, however, was reported to have significant side-effects by the study.

“The overall frequency of adverse events was significantly higher in HCQ recipients than in non-recipients,” the study showed. Gastro-intestinal events, particularly diarrhoea, were most commonly reported, similar to another study that used a high dose of HCQ, according to the study.

“Transient blurred vision was reported in one patient whose symptoms recovered two days after discontinuation of HCQ,” it said.

French study

The French RCT — conducted in March — involved those who were severely affected by COVID-19. Patients were eligible for this study if they were aged between 18 and 80 years, had confirmed SARS-CoV-2 infections and needed oxygen through masks or nasal prongs.

Among the 181 patients eligible for analysis, 84 received HCQ within 48 hours of admission (treatment group) and eight who received the drug after 48 hours, while 89 did not receive HCQ at all (control group).

The treatment group was compared to the control group.

The study found the survival rate without transfer to the intensive care unit (ICU) on day 21 was 76 per cent in the treatment group, compared to 75 per cent in the control group.

Overall survival on day 21 was 89 per cent in the treatment group and 91 per cent in the control group.

“We found that HCQ treatment at 600 mg per day added to standard care was not associated with a reduction of admissions to the intensive care unit or death in 21 days after hospital admission compared with standard care alone,” the study noted.

The rate of survival without acute respiratory distress syndrome did not increase either, according to the study.

These results remained unchanged when the eight patients who received HCQ after 48 hours were included in the analysis. This study too pointed out significant side-effects of the drug, including sudden cardiac death.

The deaths of at least two healthcare workers in India, according to media reports — one from Assam and the other from Maharashtra’s Mumbai — allegedly took place after they consumed HCQ. ICMR, however, never conducted a scientific inquiry into the deaths, the real cause of their deaths could not be ascertained.

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