Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial
MD, MPP Russell L Rothman, PhD Thomas G Stewart, MD Ahmad Mourad, MD, MPH David R Boulware, MD Matthew W Mccarthy, Florence Thicklin, Idania T Garcia Del Sol, Jose Luis Garcia, MD, MPH Carolyn T Bramante, MD, MPH Nirav S Shah, MD Upinder Singh, PharmD John C Williamson, MD, MSc Paulina A Rebolledo, MD Prasanna C Jagannathan, MD Tiffany Schwasinger-Schmidt, MD, MPH Adit A Ginde, MD, MPH Mario Castro, MD Dushyantha Jayaweera, MD Mark Sulkowski, MD Nina Gentile, MD Kathleen Mctigue, MD, MHS G Michael Felker, BS Allison Delong, MS Rhonda Wilder, MD, MSci Sean Collins, PhD Sarah E Dunsmore, PhD Stacey J Adam, MD George J Hanna, PhD Elizabeth Shenkman, MD, MHS Adrian F Hernandez, MD, MHS Susanna Naggie, PhD Christopher J Lindsell
doi:10.1101/2024.05.16.24307115
Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (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: The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and
Author Contributions Drs Rothman, Naggie, Hernandez, and Lindsell had full access to all the blinded data in the study. Dr Stewart was provided curated study data and takes responsibility for the integrity of the data analysis. All authors contributed to the drafting and review of the manuscript and agreed to submit for publication.
Disclosures
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'abstract': '<jats:p>Importance: The effect of montelukast in reducing symptom duration among outpatients '
'with mild to moderate coronavirus disease 2019 (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: The ACTIV-6 platform randomized '
'clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild '
'to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants >=30 '
'years of age with confirmed SARS-CoV-2 infection and >=2 acute COVID-19 symptoms for '
'<=7 days, were included across 104 US sites to evaluate the use of montelukast. '
'Interventions: Participants were randomized 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 at least 3 consecutive days without symptoms). Secondary '
'outcomes included time to death; time to hospitalization or death; a composite of '
'hospitalization, urgent care visit, emergency department visit, or death; COVID clinical '
'progression scale; and difference in mean time unwell. Results: Among participants who were '
'randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were '
'female, 64.6% identified as Hispanic/Latino, and 56.3% reported >=2 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 [HR] 1.02; '
'95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to '
'sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were '
'reported and 2 hospitalizations were reported in each group; 36 participants reported '
'healthcare utilization events (a priori defined as death, hospitalization, emergency '
'department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo '
'group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious '
'adverse events (3 with montelukast and 2 with placebo). Conclusions and Relevance: Among '
'outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce '
'duration of COVID-19 symptoms.</jats:p>',
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'title': 'Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The '
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