As the world rejoiced over the promising results from several COVID-19 vaccine candidates, the United States set a new record of 300,000 coronavirus deaths. This was a stark reminder that some people cannot wait for a vaccine next spring.
The ACTT-2 clinical trial recently investigated the use of both remdesivir and baricitinib, which may help with the recovery of hospitalized COVID-19 patients. The findings now appear in The New England Journal of Medicine.
Benefits of Drug Repurposing
One reason that COVID-19 is so hard to treat is that it has numerous effects on the body. These range from lung infections to neurological problems.
Drug repurposing allows for already approved drugs to expedite drug development.
Baricitinib has approval to treat rheumatoid arthritis. However, a June study in the journal EMBO Molecular Medicine showed evidence to suggest that baricitinib’s antiviral and anti-inflammatory properties helped reduce the viral load, decrease inflammation, and improve symptoms of COVID-19 in hospitalized patients.
Remdesivir, an antiviral agent that scientists initially designed to treat Ebola, is beneficial as a COVID-19 treatment. A November clinical trial in The New England Journal of Medicine revealed that people who took remdesivir had a reduced recovery time of 10 days (versus 15 days in people who took a placebo).
Currently, remdesivir is Food and Drug Administration (FDA)-approved for COVID-19 patients requiring hospitalization. However, the World Health Organization (WHO) have cautioned against using remdesivir, citing a lack of survival data to support its use for this purpose.
Therefore, researchers for the ACTT-2 trial hypothesized that combining baricitinib and remdesivir would be more effective than using either drug alone.
Clinical Trial Design
From May 8, 2020, to July 1, 2020, the clinical trial enrolled 1,033 people worldwide. Although 48% of the participants were white, 51.4% were Hispanic or Latino, 15% were Black, 9.8% were Asian, and 1% were American Indian or Alaska Native.
The diversity in trial recruitment will make the results more applicable for marginalized populations, who have a disproportionally higher risk of COVID-19 development and death.
The researchers randomly assigned a total of 515 patients to the remdesivir and baricitinib group, while 518 patients took remdesivir and a placebo.
They each received remdesivir through an intravenous line, with a 200-milligram (mg) loading dose on day 1 and a 100-mg maintenance dose for days 2 through 10.
Daily, they received 4 mg of baricitinib for 14 days or until they left the hospital. They received the anti-inflammatory drug via two oral tablets or through a nasogastric tube.
Regardless of the group the patients were in, healthcare professionals monitored them all and provided supportive care from day 1 of treatment through day 29.
“Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status, notably among patients receiving high-flow oxygen or noninvasive mechanical ventilation,” write the study authors.
Those who received remdesivir and baricitinib shortened their recovery time by a median of 1 day, compared with those who took remdesivir and a placebo.
Among those who needed high-flow oxygen or noninvasive ventilation, there was a marked difference in recovery times compared with those in the control group. By day 15, the health conditions of the patients who took remdesivir and baricitinib appeared to be improving.
People in the combination treatment group recovered by the 10th day, compared with the 18 days of recovery the scientists observed in the placebo group.
Although more participants would be necessary to measure a real difference in mortality rates, the combination treatment group appeared to have a lower mortality rate than the placebo group. However, more research is needed to confirm this.
Safety Data & Limitations
The placebo group reported 28 grade 3 or 4 adverse effects, which the investigators confirmed were associated with the treatment, while the combination group reported 25 adverse effects.
Around 5% of all the participants in the trial experienced hyperglycemia, anemia, decreased lymphocyte counts, and acute kidney injury.
Due to the differences in trial design and drug biology, the researchers could not compare their findings to those of the clinical trial that evaluated the corticosteroid dexamethasone.
Dexamethasone has emerged as a leading treatment for severe COVID-19. The New England Journal of Medicine published preliminary results of the RECOVERY clinical trial, which found that dexamethasone reduced the risk of death in severe COVID-19 cases that required treatment with oxygen.
Currently, remdesivir and baricitinib hold emergency use authorization from the FDA to treat diagnosed or suspected COVID-19 in hospitalized patients requiring supplemental oxygen, ventilation, or cardiac or respiratory life support.
The researchers say that another clinical trial for baricitinib is underway and may hold more insight into its efficacy when hospitalized patients with COVID-19 take it.
Overall, the drug combination holds promise in treating severe COVID-19. The researchers are also hopeful that this may help COVID-19 treatment become more accessible to the global community.
“Our results and the characteristics of baricitinib, including the fact that it is an oral drug with few drug-drug interactions and a good safety profile, lend itself to use in low-to-middle income countries,” they write.