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

• Published in: JAMA network open 2024-10, Vol.7 (10), p.e2439332
• Main Authors: Rothman, Russell L, Stewart, Thomas G, Mourad, Ahmad, Boulware, David R, McCarthy, Matthew W, 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
• Format: Article
• Language: English
• Subjects: Acetates - therapeutic use; Adult; Aged; Clinical trials; COVID-19; COVID-19 Drug Treatment; Cyclopropanes - therapeutic use; Double-Blind Method; Female; Health services utilization; Hospitalization - statistics & numerical data; Humans; Infectious Diseases; Leukotriene Antagonists - therapeutic use; Male; Middle Aged; Online Only; Original Investigation; Outpatients - statistics & numerical data; Quinolines - therapeutic use; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Sulfides; Treatment Outcome
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2024.39332

The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain. To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. 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. Participants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days. 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. 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). 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. ClinicalTrials.gov Identifier: NCT04885530.