Preprint: Results of Hydroxychloroquine Use Among VA Health Systems

Mixed results have led the authors of a retrospective analysis to caution use of hydroxychloroquine outside of clinical trials.

Several prospective, randomized trials of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are underway. The US Food and Drug Administration (FDA) issued an emergency use authorization for hydroxychloroquine on March 28, 2020.

The widespread present use of hydroxychloroquine for COVID-19 therapy and prophylaxis implies a need for immediate insight into clinical outcomes among patients currently being treated with hydroxychloroquine. While such results will not be as definitive as clinical trial data, they can guide clinicians in making decisions about use of the drug outside of research settings.

Investigators from the University of South Carolina, the University of Virginia, and the Columbia Veteran’s Affairs Health Care System have published a preprint detailing outcomes of hydroxychloroquine use in US veterans hospitalized with COVID-19.

While the results have not yet been peer-reviewed, the investigators found no evidence that use of hydroxychloroquine with or without azithromycin reduced the risk of mechanical ventilation. Further, there was an association of increased mortality identified in patients treated with hydroxychloroquine alone.

The investigators gathered information through a retrospective analysis of electronic health record data from patients hospitalized with SARS-CoV-2 infections in US Veterans Health Administration medical centers up to April 11, 2020.

Patients were grouped into categories pertaining to whether their standard care treatment was supplemented with hydroxychloroquine alone or with hydroxychloroquine and azithromycin.

Primary end points were mortality and whether the patient needed mechanical ventilation. The association between treatments and primary outcomes was determined using competing risk hazard regression with adjustments for clinical characteristics made using propensity scores.

Out of 368 patients evaluated in total, 97 were in the hydroxychloroquine group, 113 in the hydroxychloroquine and azithromycin group, and 158 did not receive hydroxychloroquine.

The rate of mortality was 27.8% in the hydroxychloroquine group, 22.1% in the hydroxychloroquine and azithromycin group, and 11.4% in the group which did not receive hydroxychloroquine.

The rates of mechanical ventilation were 13.3% in the hydroxychloroquine group, 6.9% in the combination therapy group, and 14.1% in the group which did not receive hydroxychloroquine.

The risk of death from any cause was higher in the hydroxychloroquine group relative to the group which did not receive hydroxychloroquine, but not in the combination therapy group. The risk for mechanical ventilation was similar in both treatment groups compared with the group which did not receive either therapy.

The investigators acknowledged the difficult situation facing clinicians and trial investigators, and the place of hydroxychloroquine in the search for a COVID-19 treatment.

“No effective therapy for COVID-19 has yet been identified. Given the longer development, testing, and approval times for novel chemical entities, repurposing drugs already approved for other indications is a promising approach to rapidly identify an effective therapy. Hydroxychloroquine is at the forefront of drug repurposing candidates,” the authors wrote.

Despite this balanced view, however, the study authors concluded that “the findings from this retrospective study suggest caution in using hydroxychloroquine in hospitalized COVID-19 patients, particularly when not combined with azithromycin.”

At present, National Institute of Health guidelines state that “there are insufficient clinical data to recommend either for or against using chloroquine or hydroxychloroquine for the treatment of COVID-19” and that “the panel recommends against the combination of hydroxychloroquine plus azithromycin because of the potential for toxicities.”

Clinicians will have to interpret the preliminary nature of these data themselves. The new information is likely to spark changes, but will not resolve the broader debate on balancing learning with doing during a period which has suddenly thrust complex clinical questions into the realm of the culture wars.