Largest analysis of hydroxychloroquine use finds no benefit for coronavirus, increased deaths

An anti-malaria drug touted by President Trump as a potential “game changer” amid the coronavirus outbreak showed no benefit for patients, according to an analysis of those hospitalized in Veterans Health Administration medical centers.

The analysis found the two primary outcomes for COVID-19 patients treated with hydroxychloroquine were death and the need for mechanical ventilation. 

The analysis was conducted retrospectively, based on data from patients hospitalized with confirmed coronavirus infections in all Veterans Health Administration medical centers until April 11.

The study analyzed only 368 patients but represented the largest look at the outcomes of COVID-19 patients treated with hydroxychloroquine — with or without azithromycin, a common antibiotic — anywhere in the world.

The popularity of hydroxychloroquine is skyrocketing, even though there is no real data that shows how it benefits patients. The popularity of both hydroxychloroquine and azithromycin has led to shortages.

While it was not a rigorous trial, the authors noted that the findings “can accelerate our understanding of the outcomes of these drugs in COVID-19 while we await the results of the ongoing prospective trials.”

Multiple prospective, randomized trials of hydroxychloroquine are currently underway and will eventually provide information about safety and efficacy. 

“However, given its increasingly widespread use, not only as therapy but also as prophylaxis for COVID-19, there is a great and immediate need to obtain insights into the clinical outcomes among patients currently treated with hydroxychloroquine, particularly because of the non-negligible toxicities associated with its use,” the authors wrote. 

The study was submitted for publication in the New England Journal of Medicine, but has not been peer-reviewed. 

The evidence on hydroxychloroquine has not been peer-reviewed either. It is conflicting, at best, and mostly anecdotal. Hospitals have widely administered the drug to patients with COVID-19 in the hope that it would help, but there has not been much evidence of its effectiveness

Hydroxychloroquine is used to treat malaria and conditions such as lupus and arthritis, and has not been approved for COVID-19.

Still, the Food and Drug Administration used its emergency authority to permit the use of hydroxychloroquine for COVID-19 in situations where clinical trials are unavailable or infeasible.

The analysis examined 97 patients treated with hydroxychloroquine alone, 113 treated with a combination of hydroxychloroquine and azithromycin, and the rest with neither drug.

According to the analysis, about 28 percent of patients who were given hydroxychloroquine plus the usual care died, versus 11 percent of those getting routine care alone.

About 22 percent of people who received hydroxychloroquine plus azithromycin also died, but the difference between that group and usual care was not considered large enough to rule out other factors.

The authors noted that hydroxychloroquine, with or without azithromycin, was more likely to be prescribed to patients with more severe disease, so increased mortality was to be expected. But the authors said high mortality rates in the hydroxychloroquine-only group persisted even after adjusting for that fact.

The researchers noted that use of hydroxychloroquine by itself did not have an impact on the need for mechanical ventilation. They noted that death might be attributable to the drug’s effects on non-respiratory vital organs. 

The side effect of hydroxychloroquine are well known, including the possibility of heart problems. A small Brazilian study was abruptly halted because some patients taking high doses developed irregular heart rates.