People who received hydroxychloroquine were less likely to die than those who did not, according to a new study.
Just 0.8 percent of patients at a facility in France who received hydroxychloroquine (HCQ) and an antibiotic died, compared to 4.8 percent of patients who did not receive the drug combination, French researchers reported on Nov. 1.
"This study represents the largest single-center study evaluating HCQ-AZ in the treatment of COVID-19. Similarly, to other large observational studies, it concludes that HCQ would have saved lives," Dr. Didier Raoult, with Aix-Marseille Universite in Marseille, and his co-authors wrote.
The paper was published in the journal New Microbes and New Infections. It was released as a preprint earlier this year, but withdrawn because authors said they have changed their "analytic strategies."
Researchers examined records from 30,423 patients with COVID-19 who were treated at another institution in Marseille, IHU Méditerranée Infection. They included all adults who tested positive for COVID-19 and who were treated in the hospital as an inpatient or an outpatient between March 2, 2020, and Dec. 31, 2021.
The study set ended up with 30,202 patients because treatment information was not available for the 221 others.
Most of the patients received off-label prescriptions of hydroxychloroquine and azithromycin (AZ), a common antibiotic.
Of the set, 23,172 patients received the drug combination. The other 7,030 did not.
Among those who received the drugs, 191, or 0.8 percent, died. Among those who did not, 344, or 4.8 percent, passed away.
Those who received HCQ and AZ were more likely to survive regardless of whether they were inpatients or outpatients.
The biggest effect was recorded in outpatients aged 50 to 89.
Limitations of the study included drawing from records from a single center. Funding came in part from the French government.
HCQ has been cleared in both France and the United States for decades but not for treating COVID-19.
Dr. David Boulware, an infectious disease doctor at the University of Minnesota Medical School, said that clinical trial data do not support using HCQ against the illness.
"Hydroxychloroquine has not been shown to have any benefit in randomized clinical trials," Dr. Boulware, who was not involved in the new study, told The Epoch Times in an email.
"There is zero antiviral effect in humans, and zero reduction in hospitalization among 11 randomized clinical trials pooled together," he added, referring to a metanalysis he co-authored that was published in January. Dr. Boulware also helped carry out a randomized trial examining HCQ as a prophylaxis in people who were exposed to COVID-19, and found it did not prevent illness or confirmed infection.
Mixed Evidence
Dr. Raoult and his co-authors acknowledged that several large randomized trials have found no benefits for HCQ against COVID-19, including a World Health Organization trial. But they said that the largest, funded by the World Health Organization and and United Kingdom government, suffered from "significant methodological problems," including high dosing during the first 24 hours.
The group also criticized smaller trials with similar findings as underpowered, including a trial in France that was stopped due to enrollment issues.
"In contrast, several large observational retrospective studies published in the literature, including a total of 47,516 patients report a benefit of using HCQ on the mortality of COVID-19 patients," the authors said, pointing to studies from France, Iran, and Spain.
They said the number of patients in the observational studies outweighs the number of patients in the randomized trials and support using HCQ as an early treatment.
Dr. Boulware said that observational data can suffer from serious problems, pointing to a response in 2020 to an observational U.S. paper that reported an association between HCQ with AZ and lower mortality among hospitalized patients.
Dr. Raoult and his co-authors acknowledged the limitations of observational data but lamented what they see as a dearth of clinical trials that use proper dosing.
"Unfortunately, few if any of the RCTs that have attempted to demonstrate the efficacy of HCQ on COVID-19 patients were run with an appropriate methodology," they wrote.
"Inadequate target (late treatment), excessive dosage of the drug, or inappropriate study power were the main troubles. While observational studies have also confounding factors, as discussed above, significant effect estimate differences between RCTs and observational studies are more likely to be linked to the quality of the study than to its design," they added, referencing a Cochrane Review that there was little difference between observational studies and clinical trials.
"In any case, since the epidemic has now vanished, it is no longer possible to conduct RCTs," they concluded. "Only observational studies can bring any more insights to support policy makers with repositioning of hydroxychloroquine in the treatment of COVID-19."
Dr. Raoult was director of the facility at which the patients were seen, but retired in 2022 after a French agency investigation found issues at the facility with regulation compliance. Several of his papers have since been retracted.
Dr. Raoult did not respond to a request for comment.
The new study came about a month after researchers in Belgium reported in another observational study that HCQ with AZ reduced COVID-19 mortality among hospitalized patients.
"Our study suggests that, despite the controversy surrounding its use, treatment with hydroxychloroquine and azithromycin remains a viable option," Dr. Gert Meeus, a nephrologist with AZ Groeninge Hospital, and other researchers wrote.
That group offered similar concerns regarding trials as the French group, including over the dosing levels.
