A 14-day course of the oral anti-inflammatory drug montelukast did not shorten symptom period in nonhospitalized US adults with gentle or reasonable COVID-19, finds a randomized managed medical trial printed right now in JAMA Community Open.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines-6 (ACTIV-6) Research Group and Investigators randomly assigned 1,250 contaminated contributors aged 30 and older to obtain a 14-day course of montelukast (10 milligrams each day) or placebo from January 27 to June 23, 2023, a interval dominated by SARS-CoV-2 Omicron subvariants. The continuing ACTIV-6 platform trial assesses repurposed medication for COVID-19 outpatients.
Drug given inside 5 days
On day 1 of the research, 3.7%, 33.2%, and 61.0% of contributors reported no, gentle, or reasonable signs, respectively. They had been enrolled inside a median of 4 days of symptom onset and acquired montelukast or placebo inside a median of 5 days.
The matched contributors had been enrolled at 140 websites throughout the nation. The median age was 53 years, 60.2% had been girls, and 56.3% reported receiving a minimum of two doses of COVID-19 vaccine.
“Montelukast, an orally lively leukotriene receptor antagonist with anti-inflammatory results, has been proven to suppress oxidative stress and cytokine manufacturing,” the researchers wrote. “Whereas montelukast is at present authorized for the therapy of bronchial asthma and allergic rhinitis, in silico screening (primarily based on in vitro research for different RNA viruses) helps the plausibility of antiviral exercise via inhibition of SARS-CoV-2 protease and polymerase enzymes.”
10-day median time to symptom decision
Time to sustained restoration, outlined as 3 or extra days with out signs, did not differ between the 628 and 622 contributors assigned to montelukast or placebo, respectively (adjusted hazard ratio [aHR]1.02; 95% credible interval [CrI]0.92 to 1.12). The unadjusted median time to symptom decision was 10 days in each teams.
These findings don’t help the usage of montelukast for the therapy of gentle to reasonable COVID-19.
By day 7, 89.8% of sufferers within the montelukast group and 89.6% of placebo recipients reported no limitations in exercise and thus did not meet the prespecified thresholds for a useful therapy impact (OR, 1.31; 95% CrI, 0.50 to 2.29). Likewise, the distinction in common symptom period was related between the montelukast and placebo teams (11.8 vs 12.0 days; distinction, −0.24 days).
Eighteen contributors (2.9%) in every group sought medical care, two (0.3%) in every group had been hospitalized, and 5 (0.4%) and three (0.5%) within the montelukast and placebo teams, respectively, skilled severe adversarial occasions. The occasions within the montelukast group had been pneumonia, lower-extremity cellulitis, and ovarian torsion. The placebo-group occasions had been pneumonia and acute appendicitis. No deaths had been reported (aHR, 1.01; 95% CrI, 0.45 to 1.84).
Analyses of a priori–outlined traits discovered that as time from symptom onset to montelukast receipt elevated past 9 days, the therapy impact favored placebo, however the researchers famous that this represented solely 28 contributors. Likewise, the therapy impact in contributors now not reporting signs on research day 1 favored placebo, however this concerned solely 41 contributors.
“These findings don’t help the usage of montelukast for the therapy of gentle to reasonable COVID-19,” the research authors concluded.
Challenges of testing drug in non-severe infections
In a associated commentaryJohn O’Horo, MD, MPH, of Mayo Clinic, famous the challenges of assessing the impact of a drug in sufferers with gentle or reasonable COVID-19.
“Early within the pandemic, when hospitalizations trended towards extra extreme sickness, it was comparatively straightforward to display a good thing about a proposed therapeutic and steadiness it towards harms in a critically sick inhabitants,” he wrote. “The security profile wanted for gentle outpatient remedy is considerably extra conservative and makes discovering an economical therapeutic more difficult.”
Presently obtainable choices for non-severe COVID-19 are costly and restricted, O’Horo stated. “Remdesivir, ritonavir-boosted nirmatrelvir, and molnupiravir have all proven some efficacy in lowering illness development, though the magnitude of these advantages is now being introduced into query, and the price of these therapeutics is excessive,” he wrote. “Monoclonal antibodies are now not obtainable, and the indications for convalescent plasma have been shrinking.”
Whereas montelukast has been dominated out as a candidate for the therapy of gentle or reasonable COVID-19, O’Horo stated the search should go on. “Till a brand new choice turns into obtainable, we’ll all have to carry our breath,” he concluded.
