Hydroxychloroquine plus common antibiotic reduces COVID mortality versus 'standard of care': study
Large Belgian study undermines FDA basis for revoking emergency use authorization, which cited heart rhythm risk.
More than three years after the FDA stripped emergency use authorization from hydroxychloroquine to treat COVID-19 in most settings, a new Belgian study finds the drug has a statistically significant advantage over the "standard of care" but only when combined with a common antibiotic.
Published in this month's issue of the Elsevier journal New Microbes and New Infections, the peer-reviewed retrospective study compared 352 adult hospitalized patients who took HCQ and azithromycin together, versus 10 times as many who only received the "standard of care" with no other COVID treatments.
It builds on a much larger "national retrospective cohort study" that found a 32% reduction in mortality for patients receiving low-dose HCQ versus the standard of care, but that study didn't include patients from AZ Groeninge Hospital, which "adopted a strategy" of HCQ-plus-azithromycin for all patients, the researchers wrote.
The 28-day mortality rate was 57% higher for the control group, and the "survival benefit in the treatment group was consistent across all age groups," the researchers found.
The crude mortality rate for each was 16.8% for HCQ plus azithromycin and 25.9% for standard of care, and average age of death was 84 years.
"This result is remarkable because treatment with hydroxychloroquine was abandoned following the results of the SOLIDARITY and RECOVERY trial, which did not find a clinical benefit," the paper says.
The control group was taken from the Belgian Collaborative Group on COVID-19 Hospital Surveillance, composed of patients with "PCR-confirmed COVID-19" between March 14 and May 24, 2020.
While younger on average, the treatment group was actually more likely to have severe comorbidities including obesity, compromised immune system, arterial hypertension, liver disease and lung disease, though the researchers adjusted for these variables before calculating odds ratios.
They found no episodes of "ventricular arrhythmia or torsade de pointes," or abnormal heart rhythms, during treatment. The FDA's stated basis for rescinding EUA was "risk of heart rhythm problems."
The combination treatment was "safe and generally well-tolerated," they wrote. "In view of safety concerns about cardiac toxicity, our data are reassuring" and accord with "other studies that found no increase in severe cardiac arrhythmias, even when higher doses of hydroxychloroquine were used."
The researchers theorize that randomized controlled trials found no benefit because they "often reserved treatment for severely ill patients" but also used a much higher dose, including the aforementioned SOLIDARITY and RECOVERY trials. Other RCTs with low dosages "were not adequately powered to demonstrate a survival benefit of the magnitude that was seen in our study."
While they are cautious about "to what extent our data still apply in the current phase of the pandemic," the researchers emphasize that new COVID variants, the expense of "novel treatments like nirmatrelvir/ritonavir" (Pfizer's Paxlovid) and "severe medication interactions" means the low-cost, low-risk HCQ-azithromycin combination "remains a viable option."
The FDA did not immediately respond to a request for its response to the study, which challenges the FDA's basis for revoking EUA.