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All Studies   Meta Analysis    Recent:   

Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial

Rothman et al., medRxiv, doi:10.1101/2024.05.16.24307115, ACTIV-6, NCT04885530
May 2024  
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Hospitalization 1% Improvement Relative Risk Hosp./ER 1% Progression, day 28 32% Progression, day 14 -41% Progression, day 7 24% Recovery 2% Recovery time 2% Montelukast  ACTIV-6  LATE TREATMENT  DB RCT Is late treatment with montelukast beneficial for COVID-19? Double-blind RCT 1,250 patients in the USA (January - June 2023) Lower progression with montelukast (not stat. sig., p=0.29) c19early.org Rothman et al., medRxiv, May 2024 Favorsmontelukast Favorscontrol 0 0.5 1 1.5 2+
28th treatment shown to reduce risk in November 2021
 
*, now with p = 0.0045 from 8 studies.
Lower risk for mortality, hospitalization, and cases.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 81 treatments. c19early.org
RCT 1,250 outpatients with mild to moderate COVID-19 showing no significant difference in time to sustained recovery with montelukast treatment. There were no deaths and only 2 hospitalizations in each group.
Notably, results were better with patients that had mild COVID-19 at baseline compared to moderate/severe cases, and overall efficacy is reduced by poor results with extremely late treatment 9 days after onset, and with patients that had no symptoms at baseline.
Authors note the treatment drug was recalled and replaced from another source but do not report why the drug was recalled. Authors describe previous research testing 10mg and 20mg doses, noting that only 20mg showed improved pulmonary function testing, however authors do not indicate why they chose to test the lower dose.
It is unclear why authors report all-cause hospitalization and urgent care rather than COVID-19 specific outcomes. Given the low rate of urgent care visits and hospitalization, and the expected baseline frequency of these events independent of COVID-19, most or all of these events may be unrelated to COVID-19.
Authors note that previous research showed improvements specifically for cough, and authors collected cough data, however no results for cough are reported.
risk of hospitalization, 1.0% lower, RR 0.99, p = 1.00, treatment 2 of 628 (0.3%), control 2 of 622 (0.3%), NNT 32551.
hosp./ER, 1.0% lower, RR 0.99, p = 1.00, treatment 18 of 628 (2.9%), control 18 of 622 (2.9%), NNT 3617.
risk of progression, 32.4% lower, OR 0.68, p = 0.29, inverted to make OR<1 favor treatment, clinical progression, day 28, RR approximated with OR.
risk of progression, 40.8% higher, OR 1.41, p = 0.82, inverted to make OR<1 favor treatment, clinical progression, day 14, RR approximated with OR.
risk of progression, 23.7% lower, OR 0.76, p = 0.27, inverted to make OR<1 favor treatment, clinical progression, day 7, RR approximated with OR.
risk of no recovery, 2.0% lower, HR 0.98, p = 0.71, treatment 628, control 622, inverted to make HR<1 favor treatment.
recovery time, 2.0% lower, relative time 0.98, p = 0.07, treatment mean 11.77 (±2.49) n=628, control mean 12.01 (±2.16) n=622.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Rothman et al., 18 May 2024, Double Blind Randomized Controlled Trial, placebo-controlled, USA, preprint, median age 53.0, 32 authors, study period 27 January, 2023 - 23 June, 2023, trial NCT04885530 (history) (ACTIV-6). Contact: susanna.naggie@duke.edu.
This PaperMontelukastAll
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
References
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Copertino, Duarte, Powell, De Mulder Rougvie, Nixon, Montelukast drug activity and potential against severe actue respiratory syndrome coronavirus 2 (SARS-CoV-2), J Med Virol
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Hammond, Fountaine, Yunis, Nirmatrelvir for vaccinated or unvaccinated adult outpatients with Covid-19, N Engl J Med
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Hm, Gareeb, Almulaiky, Cruz-Martins, Batiha, Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity, Eur J Pharmacol
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Mccarthy, Naggie, Boulware, Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial, JAMA
Naggie, Boulware, Lindsell, Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial, JAMA
Sanghai, Tranmer, Taming the cytokine storm: repurposing montelukast for the attenuation and prophylaxis of severe COVID-19 symptoms, Drug Discov Today
Soltani, Nasirharandi, Khorvash, Nasirian, Dolatshahi et al., The effectiveness of gabapentin and gabapentin/montelukast combination compared with dextromethorphan in the improvement of COVID-19-related cough: A randomized, controlled clinical trial, Clin Respir J
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Between January 27, 2023, and June 23, 2023, 1250 participants &gt;=30 ' 'years of age with confirmed SARS-CoV-2 infection and &gt;=2 acute COVID-19 symptoms for ' '&lt;=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 &gt;=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). 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Late treatment
is less effective
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