The results were the latest development on a highly charged medical and political issue - the efficacy of hydroxychloroquine in combating covid-19.
In March, Trump said hydroxychloroquine used in combination with the antibiotic azithromycin had "a real chance to be one of the biggest game changers in the history of medicine" with little evidence to back up that claim.
The trial found that 107 of the 821 test participants developed COVID-19 - both confirmed and probable cases - during the 14 days in which they were followed after being exposed.
"Amongst those who received hydroxychloroquine, 49 developed the disease (or compatible symptoms such as fever or cough), vs. 58 in the group that received the placebo". Such a study is considered the gold standard for clinical trials.
Adding to the controversy surrounding the drug, a large observational study on hydroxychloroquine that warned of risky side effects has come under fire in recent days.
Several trials of the drug have been stopped over concerns about its safety for treating COVID-19 patients raised by health regulators and previous less rigorous studies and. That was not a statistical difference, the release stated.
The U.S. Food and Drug Administration cautioned in late April against the use of hydroxychloroquine in patients with heart disease due to an increased risk of risky cardiac rhythm problems.
"This is not some sideshow or minor issue", said Dr. Walid Gellad, a professor at University of Pittsburgh's medical school, who was not a signatory of the letter but has been critical of the study. In addition, the company has not explained its methodology, scientists say.
People given hydroxychloroquine were more likely to report side-effects such as nausea and stomach pain - 40% versus 17%. The researchers said the data discrepancy did not affect the study's findings.
David Boulware, an infectious disease specialist at the University of Minnesota and senior investigator of the study, said he launched the trial because hydroxychloroquine had shown activity in a lab setting against the coronavirus. He later said he took the drugs preventively after two people who worked at the White House were diagnosed with COVID-19, the illness caused by the novel coronavirus.
The participants were recruited on the Internet through social media.
"I think both sides - one side who is saying "this is a unsafe drug" and the other side that says "this works" - neither is correct", said Boulware.
"So if some were for Trump, and some were not Trump supporters all that would be washed out because the trial was blinded", he said.
"We conducted an worldwide, randomized controlled trial to look at whether the use of hydroxychloroquine in patients who'd had a high-risk exposure to COVID-19 would prevent the development of symptomatic disease compared to placebo", Lee said in an interview.
Among the most outspoken critics of The Lancet study has been French professor Didier Raoult, whose own work has been at the forefront of promoting hydroxychloroquine and has also been subject to criticisms over methodology.
Boulware said that the analysis tried to drill down on whether any subgroups, by race, occupation, age, or co-morbidities, had any hint of benefit.