Yet Another Study Shows Hydroxychloroquine Ineffective in COVID-19
Researcher in Brazil published a study in The New England Journal of Medicine finding that hydroxychloroquine, alone or with antibiotic azithromycin, did not help hospitalized patients with mild-to-moderate COVID-19.
The drug was once touted by President Trump as a “game-changer” despite skepticism from many physicians and researchers. Although there have been a few studies suggesting the drug or combination may have some positive effects, the preponderance of studies appears to be shifting toward the drug’s lack of effectiveness and even potential harm in treating COVID-19 patient.
On March 30, the U.S. Food and Drug Administration (FDA) granted hydroxychloroquine and chloroquine Emergency Use Authorization (EUA) for COVID-19. On June 15, the agency revoked the EUA. The FDA indicated at the time that, based on new data, there was no enough supporting evidence for the two drugs to be considered effective in treating COVID-19.
The study out of Brazil evaluated 667 patients, 504 who had confirmed COVID-19 and were included in a modified intention-to-treat analysis. It was conducted at 55 hospitals in Brazil. The hospitalized patients had either suspected or confirmed COVID-19 and were receiving either no supplemental oxygen or a maximum of four liters per minute of supplemental oxygen. The patients were randomized 1:1:1 to receive standard care, standard care plus hydroxychloroquine at 400 mg twice a day, or standard care plus hydroxychloroquine 400 mg twice a day plus azithromycin 500 mg once a day for seven days.
The primary endpoint was clinical status at 15 days assessed using a seven-point ordinal scale, with levels ranging from one to seven and higher scores indicating a worse condition. They also evaluated safety.
The study found that compared to standard care, “the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone or hydroxychloroquine plus azithromycin.” In plainer language, the drugs did not appear to have any benefit.
In addition to the efficacy, or lack of it, the researchers observed unusual heart rhythms and elevated liver enzymes in the patients receiving hydroxychloroquine or the hydroxychloroquine-azithromycin combination.
The research was funded by the Coalition COVID-19 Brazil and EMS Pharma, a Brazilian pharmaceutical company.
One of the positive studies was conducted by researchers at Henry Ford Health System in the Detroit Metropolitan Area in Michigan. Not unexpectedly, the Trump Administration jumped on the news in early July of that study as support for the president’s assertions of hydroxychloroquine’s effectiveness. For the most part, the FDA declined to get involved in that debate once again.
Luciana Borio, who was the agency’s acting chief scientist from 2017 to 2019, told STAT in early July, “The FDA cannot afford another misstep if it wants to maintain credibility with American people, which is going to be so essential when doing a broad vaccine program, should we identify a safe and effective vaccine for COVID.”
The Ford Health System study was criticized because it was not randomized, and because patients who received hydroxychloroquine were also more likely to be dosed with steroids, which seem to help the sickest patients with the disease. Critics believe this influenced the central premise of the study, that death rates were 50% lower in hospitalized patients receiving hydroxychloroquine.
Steven Nissen, a cardiologist at the Cleveland Clinic told STAT, in response to the early-July announcement by President Trump’s trade adviser, Peter Navarro, that they were considering re-issuing the EUA, said, “The medical community has come to the inescapable conclusion that hydroxychloroquine is not effective at treating COVID-19 infections. Peter Navarro is not a scientist, he is the president’s trade representative. He should not be advising the public on matters of health.”
The Ford study is further undermined by increasing evidence that steroids, particularly dexamethasone, appear effective in decreasing the severity of COVID-19. The first trial out of the UK was on dexamethasone, but newer studies, such as one at the Albert Einstein College of Medicine and Montefiore Health System, have found that another steroid in the same family as dexamethasone, prednisone, decreased risk of going on mechanical ventilation or dying by 75%. The study was published in the Journal of Hospital Medicine.
And promisingly, the Einstein-Montefiore study found that the use of a blood test for C-reactive protein, an enzyme produced in the liver in response to inflammation, was able to help identify which patients would benefit from steroids and at what point in the disease.
“Our findings suggest that steroid therapy should be reserved for people with high inflammation,” said senior author William Southern. “It’s a different story for people who do not have significant inflammation; For them, any benefit is outweighed by the risks from using steroids.”