Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo: The ACTIV-6 Randomized Clinical Trial. Academic Article uri icon

Overview

abstract

  • IMPORTANCE: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain. OBJECTIVE: To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial (Accelerating COVID-19 Therapeutic Interventions and Vaccines [ACTIV]-6) was conducted from January 27 through June 23, 2023, during the circulation of Omicron subvariants. Participants aged 30 years or older with confirmed SARS-CoV-2 infection and 2 or more acute COVID-19 symptoms for less than 7 days were included across 104 US sites. INTERVENTIONS: Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days. MAIN OUTCOMES AND MEASURES: The primary outcome was time to sustained recovery (defined as ≥3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of health care utilization events (hospitalization, urgent care clinic visit, emergency department visit, or death); COVID-19 clinical progression scale score; and difference in mean time unwell. A modified intention-to-treat approach was used for the analysis. RESULTS: Among 1250 participants who were randomized and received the study drug or placebo, the median age was 53 years (IQR, 42-62 years), 753 (60.2%) were female, and 704 (56.3%) reported receiving 2 or more doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [AHR], 1.02; 95% credible interval [CrI], 0.92-1.12; P = .63 for efficacy). Unadjusted median time to sustained recovery was 10 days (95% CI, 10-11 days) in both groups. No deaths occurred, and hospitalizations were reported for 2 participants (0.3%) in each group; the composite of health care utilization events was reported for 18 participants (2.9%) in the montelukast group and 18 (2.9%) in the placebo group (AHR, 1.01; 95% CrI, 0.45-1.84; P = .48 for efficacy). Five participants (0.4%) experienced serious adverse events (3 [0.5%] in the montelukast group and 2 [0.3%] in the placebo group). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial of outpatients with mild to moderate COVID-19, treatment with montelukast did not reduce duration of COVID-19 symptoms. These findings do not support the use of montelukast for the treatment of mild to moderate COVID-19. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04885530.

authors

  • Rothman, Russell L
  • Stewart, Thomas G
  • Mourad, Ahmad
  • Boulware, David R
  • McCarthy, Matthew William
  • Thicklin, Florence
  • Garcia Del Sol, Idania T
  • Garcia, Jose Luis
  • Bramante, Carolyn T
  • Shah, Nirav S
  • Singh, Upinder
  • Williamson, John C
  • Rebolledo, Paulina A
  • Jagannathan, Prasanna
  • Schwasinger-Schmidt, Tiffany
  • Ginde, Adit A
  • Castro, Mario
  • Jayaweera, Dushyantha
  • Sulkowski, Mark
  • Gentile, Nina
  • McTigue, Kathleen
  • Felker, G Michael
  • DeLong, Allison
  • Wilder, Rhonda
  • Collins, Sean
  • Dunsmore, Sarah E
  • Adam, Stacey J
  • Hanna, George J
  • Shenkman, Elizabeth
  • Hernandez, Adrian F
  • Naggie, Susanna
  • Lindsell, Christopher J

publication date

  • October 1, 2024

Research

keywords

  • Acetates
  • COVID-19
  • COVID-19 Drug Treatment
  • Cyclopropanes
  • Quinolines
  • SARS-CoV-2
  • Sulfides

Identity

Digital Object Identifier (DOI)

  • 10.1001/jamanetworkopen.2024.39332

PubMed ID

  • 39422912

Additional Document Info

volume

  • 7

issue

  • 10