By Michael Erman and Ankur Banerjee

(Reuters) – The anti-malarial drug hydroxychloroquine, which U.S. President Donald Trump says he has been taking and has urged others to use, was tied to an increased risk of death in hospitalized COVID-19 patients, a large study published on Friday showed.

In the study that looked at more than 96,000 people hospitalized with COVID-19, the respiratory disease caused by the novel coronavirus, those treated with hydroxychloroquine or the related chloroquine had higher risk of death and heart rhythm problems than patients who were not given the medicines.

The study, published in the Lancet medical journal, showed no benefit for coronavirus patients taking the drugs.

Demand for the decades-old hydroxychloroquine has surged as Trump repeatedly promoted its use against the coronavirus, urging people to try it. “What have you got to lose?” he asked.

Trump said this week he has been taking hydroxychloroquine as a preventative medicine despite a lack of scientific evidence.

The Lancet study authors suggested that hydroxychloroquine and chloroquine should not be used to treat COVID-19 outside of clinical trials until studies confirm their safety and efficacy in such patients.

There is a frantic search for drugs to treat COVID-19 at the same time that multiple research teams pursue a safe and effective vaccine to combat a pathogen that has killed more than 335,000 people worldwide and sickened millions more.

The U.S. Food and Drug Administration has allowed healthcare providers to use the drugs for COVID-19 through an emergency-use authorization, but has not approved them to treat it.

Dr. Mandeep Mehra, one of the study’s authors, said the research shows that the FDA should withdraw that authorization.

“That will help move this towards more, stronger evidence because it will then force the use of these drugs only in the setting of control trials,” Mehra said in an interview. “That would be an extremely wise decision.”

The FDA has said that, for safety reasons, hydroxychloroquine should be used only for hospitalized COVID-19 patients or those in clinical trials. The drug has been tied to dangerous heart rhythm problems.

The Lancet study looked at data from 671 hospitals where 14,888 patients were given either hydroxychloroquine or chloroquine, with or without an antibiotic, and 81,144 patients were not given such treatments.

Both drugs have shown evidence of effectiveness against the coronavirus in a laboratory setting, but studies in patients had proven inconclusive. Several small studies in Europe and China spurred interest in using hydroxychloroquine against COVID-19, but were criticized for lacking scientific rigor.

Several more recent studies have not shown the drug to be an effective COVID-19 treatment. Last week, two studies published in the medical journal BMJ showed that patients given hydroxychloroquine did not improve significantly over those who were not.

Hydroxychloroquine is used to treat lupus and rheumatoid arthritis as well as malaria.

Hospitalized patients tend to have a more severe version of COVID-19. Some proponents of the drugs for COVID-19 argue that they may need to be administered at an earlier stage to be effective.

There are ongoing randomized, controlled clinical trials to study the drug’s effectiveness in preventing infection by the coronavirus as well as treating mild to moderate COVID-19. Some of those may yield results within weeks.

(Reporting by Ankur Banerjee and Manas Mishra in Bengaluru and Michael Erman in New York; Editing by Saumyadeb Chakrabarty, Bill Berkrot, Jonathan Oatis and Will Dunham)