- For the third time this month, researchers running a large clinical trial in the U.K. have released results likely to shape how physicians the world over treat COVID-19.
- On Tuesday, investigators for the RECOVERY study announced that treatment with Kaletra, an antiviral therapy for HIV, was no better than usual care alone in preventing death among patients hospitalized with coronavirus disease. As a result, the trial committee decided to stop giving the drug in the study.
- Only summary results are currently available, and the data has not yet been peer reviewed or published. But the findings from RECOVERY carry weight, as the trial involves thousands of patients randomized to receive either experimental treatments or standard supportive therapy.
Two weeks ago, the RECOVERY investigators surprised the world with results showing dexamethasone, a cheap, widely available steroid, reduced the risk of dying among patients who were gravely ill with coronavirus disease. It was the first time a drug had been shown in a randomized, controlled study to help keep COVID-19 patients alive.
The data provided then, which are now available in an unpublished manuscript, quickly led health agencies to revisit guidelines on using the steroid. The U.K.'s National Health Service immediately authorized dexamethasone for treatment of COVID-19, and the U.S. National Institutes of Health recommended the drug be given to patients on mechanical ventilation or oxygen support — the two groups shown in RECOVERY to benefit from treatment.
The World Health Organization, meanwhile, said it would update its clinical guidance to incorporate the trial findings.
RECOVERY's determination that Kaletra, which contains the drugs lopinavir and ritonavir, provides no benefit is less surprising, but could also shape COVID-19 treatment.
Kaletra was one of many antiviral therapies quickly thrust into clinical testing when COVID-19 emerged early this year. The outlook for the drug dimmed considerably, however, after a small study in China found the drug didn't help patients recover any faster than those given supportive care.
Still, debate over the drug's potential usefulness continued, in part due to the trial's size as well as questions over whether the drug was given too late.
While detailed questions won't be answerable until the full data are available, RECOVERY's findings further diminish the likelihood Kaletra can play a role in treating COVID-19.
A total of 1,596 patients were randomized to receive Kaletra in RECOVERY, and were compared to 3,376 patients who were treated with standard supportive care. Most of the patients — 70% — were on oxygen support at the time of randomization, while roughly a quarter were not yet receiving oxygen.
After 28 days, 22% of the patients given Kaletra had died versus 21% given placebo. Investigators observed no beneficial effects to treatment in lowering the risk of progression to mechanical ventilation, or on reducing the length of hospital stay.
"These data convincingly rule out any meaningful mortality benefit of lopinavir-ritonavir in the hospitalized COVID-19 patients we studied," the investigators said in a statement.
Only 4% of patients studied were on ventilators at baseline, too few for the investigators to draw any conclusions about the drug's usefulness in those patients. Antiviral therapies like Kaletra, however, are thought to work best when given early on in the course of an infection.
In addition to the results on dexamethasone and Kaletra, RECOVERY has also found hydroxychloroquine, the much-debated malaria pill, did not help patients hospitalized with COVID-19 survive or recover faster any more than standard treatment.
Detailed data on the hydroxychloroquine result are not yet available, nor have they been peer reviewed.