An anti-malaria drug that has been trumpeted as a therapy for COVID-19 was unable in a University of Minnesota clinical trial to prevent the onset of the infectious disease.

Many prescribers had given it off-label to COVID-19 patients — in the absence of other options — and President Donald Trump had been an early champion of the drug and said in mid-May that he was taking it for the preventive benefit, a benefit that the U study could not verify.

Results published online Wednesday by the New England Journal of Medicine showed little difference in the onset of COVID-19 in 414 people who took hydroxychloroquine and a comparison group of 407 that took only folic acid vitamins.

There was a small difference, as 11.8% of people taking the drug developed COVID-19, compared with 14.3% of those taking vitamins, the study showed.

Even if valid, the small difference means that 42 people would have to take the drug prophylactically to prevent one COVID-19 case.

The study provides evidence only of whether the drug is effective in preventing COVID-19 onset following exposure to someone with the infection.

Anxiety about COVID-19 was reflected last week in a study in the Journal of the American Medical Association, which showed a twentyfold surge in prescriptions of hydroxychloroquine and a similar drug, chloroquine, in late March after the World Health Organization declared a COVID-19 pandemic and the president tweeted March 19 in favor of the drug.

The U trial was the first in the world to assess whether hydroxychloroquine could prevent the onset of COVID-19 in people exposed to the novel coronavirus that causes it, and the first placebo-controlled double-blind study of the drug’s effect on COVID-19.

Critics on one side felt hydroxychloroquine was a wonder drug and that all study participants should receive it, while critics on the other side felt it was too dangerous to study, Boulware said.