Treatment with hydroxychloroquine alone or in combination with azithromycin was associated with a reduced in-hospital mortality risk in a study of patients hospitalized with coronavirus disease 2019 (COVID-19), according to findings published in the International Journal of Infectious Diseases.1

After adjusting for COVID-19 risk factors, recipients of hydroxychloroquine or hydroxychloroquine plus azithromycin had a 66% and 71% decreased risk of in-hospital mortality, respectively, compared with those not receiving either drug, Samia Arshad, MPH, of the Henry Ford Hospital in Detroit, Michigan, and colleagues reported. Azithromycin alone was not significantly associated with mortality risk.

“Considered in the context of current studies on the use of hydroxychloroquine for COVID-19, our results suggest that hydroxychloroquine may have an important role to play in reducing COVID-19 mortality,” the investigators wrote.

Other studies of hydroxychloroquine as a treatment for patients with COVID-19 have yielded variable results. For example, Arshad and colleagues noted, a randomized controlled study of 62 patients with COVID-19 in China found that hydroxychloroquine treatment was associated with a shorter duration of fever and time to resolution of cough and pneumonia.2 A study of 1376 patients hospitalized with COVID-19 in New York, however, found no significant reduction in the risk of death or intubation among patients who were treated with hydroxychloroquine compared with those who were not.3


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In June of this year, the US Food and Drug Administration (FDA) revoked its emergency use authorization for hydroxychloroquine and chloroquine as a treatment for COVID-19 in certain hospitalized patients when a clinical trial is unavailable or participation is not feasible.

“We made this determination based on recent results from a large, randomized clinical trial in hospitalized patients that found these medicines showed no benefit for decreasing the likelihood of death or speeding recovery,” stated an announcement on the FDA website.4

Arshad and colleagues included 2541 patients hospitalized with COVID-19 at 6 hospitals within the Henry Ford Health System in Southeast Michigan. The patients, who had a median age of 64 years, had a median total hospitalization time of 6 days and median time to follow-up of 28.5 days. The most common comorbidities were hypertension (65.4%), chronic lung disease (63.7%), chronic kidney disease (43.3%), and diabetes mellitus (37.6%). Of the 2541 patients included, 1202 received hydroxychloroquine alone, 147 received azithromycin alone, 783 received a combination of these drugs, and 409 did not receive either drug.

The overall in-hospital mortality rate was 18.1%, but the rate varied according to treatment status. The rates were 13.5%, 22.4%, and 20.1% for those who received hydroxychloroquine alone, azithromycin alone, and hydroxychloroquine plus azithromycin, respectively, compared with 26.4% among patients who received neither medication. Of the 460 deaths that occurred, 88% were due to respiratory failure.

“Findings of this observational study provide crucial data on experience with hydroxychloroquine therapy, providing necessary interim guidance for COVID-19 therapeutic practice,” according to the investigators.

Clinicians dosed hydroxychloroquine at 400 mg twice daily for 2 doses on day 1, followed by 200 mg twice daily on days 2-5, and dosed azithromycin at 500 mg once daily on day 1 followed by 250 mg once daily for the next 4 days, according to the investigators. “The combination of hydroxychloroquine [with] azithromycin was reserved for selected patients with severe COVID-19 and with minimal cardiac risk factors,” they noted.

The investigators said their findings support recent guidelines from the National Institutes of Health that indicate a potential role for hydroxychloroquine in treating patients hospitalized with COVID-19 without co-administration of azithromycin. “However, our results should be interpreted with some caution and should not be applied to patients treated outside of hospital settings. Our results require confirmation in prospective, randomized controlled trials that rigorously evaluate the safety and efficacy of hydroxychloroquine therapy for COVID-19 in hospitalized patients.”

The authors acknowledged certain study limitations, including the retrospective, nonblinded, and nonrandomized design as well as lack of information on duration of symptoms prior to hospitalization.

References

  1. Arshad S, Kilgore P, Chaudhry ZS, et al. Treatment with hydroxychloroquine, azithromycin, and combination in patients with COVID-19. Int J Infect Dis. 2020;97:396-403.
  2. Chen Z, Hu J, Zhang Z, et al. Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial [published online April 10, 2020]. MedRxiv. doi: 10.1101/2020.03.22.20040758
  3. Geleris J, Sun Y, Platt J, et al. Observational study of hydroxychloroquine in hospitalized patients with Covid-19. N Engl J Med. 2020;382(25):2411-2418. doi: 10.1056/NEJMoa2012410
  4. FDA cautions against the use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems. U.S. Food and Drug Administration. Published April 1, 2020. Updated July 1, 2020. Accessed July 28, 2020.