The researchers found that those who took chloroquine or hydroxychloroquine were more likely to develop serious cardiac arrhythmias, or irregular heartbeats.
The drugs are approved for other uses, but not for the treatment of COVID-19. Early on in the COVID-19 pandemic, Trump labeled the drugs potential "game changers" against the disease, despite little good evidence supporting such claims. Google searches by Americans looking for the medicines surged after his endorsement.
President Trump repeatedly has pushed the malaria drugs, even admitting to taking hydroxychloroquine to try to prevent infection or minimise symptoms from the coronavirus.
A trial is under way to see whether the anti-malarial drug could prevent Covid-19. And its authors say it may offer the most definitive proof yet.
It determined that not only was there "an absence of benefit" from treatments using the drugs, it said they "could even be harmful" to the patients whom receive it as a treatment.
"This is the first large-scale study to find statistically robust evidence that treatment with chloroquine or hydroxychloroquine does not benefit patients with Covid-19", Mandeep Mehra, executive director of the Brigham and Women's Hospital Centre for Advanced Heart Disease in Boston, said.More news: National Hockey League looking to confirm playoff teams
The patients were admitted to 671 hospitals between December 20 and April 14, and all had either been discharged or had died by April 21. Of this population, 1,868 patients received chloroquine, 3,783 received chloroquine with a macrolide, 3,016 received hydroxychloroquine, and 6,221 received hydroxychloroquine with a macrolide.
It found that those who were treated with chloroquine, hydroxychloroquine through four methods all died at a higher rate than those who did not received the drug. The results on these patients, from a long-established global research database, are "as real world as a database can get", he said. The other 81,144 patients served as a control group.
The highest rate (8%) was among patients given hydroxychloroquine and an antibiotic, compared with 0.3% of patients in the control group.
"Instead, our findings suggest it may be associated with an increased risk of serious heart problems and increased risk of death".
Only one drug, Gilead Sciences Inc.'s remdesivir, has been shown to benefit coronavirus patients in a clinical trial.
After taking into account age, smoking, various health conditions and other factors that affect survival, researchers estimate that use of the drugs may have contributed to 34% to 45% of the excess risk of death they observed.More news: Jordan Henderson sends message to Chelsea FC star N’Golo Kante
Prior studies have concluded much the same.
More than 96,000 people, all of whom had been hospitalized with COVID-19, were included in the study.
The US Food and Drug Administration has said hydroxychloroquine should only be used for hospitalised Covid-19 patients or those in clinical trials.
The FDA also warned that "hydroxychloroquine and chloroquine can cause abnormal heart rhythms".
According to the largest study on the subject, which involved more than 96,000 hospitalized patients with COVID-19 on six continents. Those who received hydroxychloroquine fared no better than those who did not.
About 9% of patients taking none of the drugs died in the hospital, versus 16% on chloroquine, 18% on hydroxychloroquine, 22% on chloroquine plus an antibiotic, and 24% on hydroxychloroquine plus an antibiotic.More news: Brazil passes 20,000 virus deaths after record 24-hour toll