Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo
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. ,   Accelerating COVID-19 Therapeutic Interventions and Vaccines–6 Study Group and Investigators, Hanna George , Fraser Ryan , Ward Mark , Gamboa Jackson Jennifer , McAdams M. Patricia , Vail Julia , Korzekwinski Kayla , Oyelakin Martina , Chopp Julie , Randle Desmon , Dockery Samantha , Adkins Rodney , Crow Matthew , Nowell Erin , Wells Kadie , Herbert Alicia , Stone Allegra , Heavlin Heather , Brown Linley , Harding Tina , Harrington Amanda , Beauchaine Meaghan , Lindblom Kelly , Burns Andrea , Aamodt David , Collins Jess , Dixon Sheri , Gao Yue , Graves John , Grindstaff James , Harrell Frank , Lai Jessica , Liao Vicky , Lopez Itzel , Manis Elizabeth , Mankowski Kalley , Marlin Jessica , Merkel Alyssa , Nwosu Sam , Obregon Savannah , Orozco Dirk , Prato Nelson , Rhode Max , Shirey-Rice Jana , Vermillion Krista , Smith Jacob , Tan Hsi-nien , Vance Meghan , Weir Maria , Bianchi Ray , Premas Jen , Gupta Madhu , Karawan Greg , Lima Santia , Ziomek Carey , Arena Joseph , DeAlmeida Sonaly , Malik Anuj , Bryce Jane , Swint Sarah , Ramin Soroush , Nataraj Jaya , Deider Julien , Cruz Ricardo , Ramirez Ana Maria , Henault Lori , Marcus Joseph , Southwell Alexis , Jacques Genice , Sexton Cedar , Tiffany Brian , Tanner Charlotte , Sahelian Allegra , George-Adebayo Constance , Adebayo Adeolu , Zapatero Jose , Clement Julie , Ronan Theresa , Woods Ashley , Gallegos Christopher , Flys Tamara , Sloan Olivia , Olofintuyi Anthony , Samraj Joshua , Vasbinder Alma , Averett Amaya , Slandzicki Alex , Wallen Jessica , Vogel Claudia , Munoz Sebastian , Kavtaradze David , Watson Casandra , Singleton David , Sevier Marcus , Rivon Maria , Del Pilar Arnold , Spangler Amber , Rao Sohail , Cantu Luis , Krishna Arvind , Daugherty Heidi , Kerr Brandi , Evans Kathy , Spees Robert , Marta Mailyn , Dolor Rowena , Vergara Lorraine , Jordan Jackie , Burruss Valencia , Hurst Terri , Ofotokun Igho , Zhang Cecilia , Traenkner Jessica , Atha Mary M. , Prabhu Rajesh , Klicka Krystal , Lightfeather Amber , James Vickie , Rogers Marcella , Oragwu Chukwuemeka , Oguego Ngozi , Pillai Rajesh , Gabriel Ahab , Ghaly Emad , Michal Marian , Vasquez Michelle , Mamon Angela , Sheets Michelle , Hassanien Gammal , Ismail Samah , Samir Yehia , Meltzer Andrew , Shahamatdar Soroush , Heidish Ryan S. , Loganathan Aditya , Brehaut Scott , Roche Angelina , Mehta Manisha , Koppinger Nicole , Baez Jose , Pagan Ivone , Abdelsayed Dallal , Aziz Mina , Robinson Philip , Lozinski Grace , Nguyen Julie , Griffin Alvin , Morris Michael , Love Nicole , Mattox Bonnie , Martin Raykel , Pardue Victoria , Rowland Teddy , Ruiz-Unger Juan , Reyes Lionel , Zamora Yadira , Bacallao Navila , Cienki John , Cohen Jonathan , Yuan Ying , Li Jenny , Szeto Jeremy , Stelmash Lauren , Mekhael Sara , Morales Castillo Ledular , Gutierrez Anya , Prieto Sabrina , Amon Arch , Barbera Andrew , Bugajski Andrew , Willis Walter , Jacklin Kellcee , Lamb Deryl , Harper Amron , Stout Elmer , Griffin Merischia , Pyram-Bernard Nancy , Quintero Arlen , Clark Nina , Barsanti-Sekhar Mary , Carbrera-Mendez Christina , Evans Mary Rose , Adhami Eftim , Carillo Giovanni , Maria Josette , Paudel Diksha , Raymond Oksana , Summers Jeffrey , Turner Tammy , Lenert Leslie , Panaccione Ebony , Szwast Elizabeth , Reynolds Amy , Abdulghani Ahsan , Vasoya Pravin , Miller Conrad , Wiley Hawa , Chan Austin , Khizer Saadia , Adeyemi Oluwadamilola , Chi Wei Ning , Chen July , Morton-Jost Melissa , Castex Julie , Quirch Ali , Belani Hrishikesh , Machicado Rosario , Bjornsson Bjorn , Olivo Jacqueline , Maldonado Maria , Vecchiarelli Anthony , Gaytan-Alvarez Diana , Cherukuri Vijaya , Alicic Radica , Lambert Allison A. , Urbat Carissa , Baxter Joni , Cooper Ann , Linn Dawn , Fisher Laura , Patel Vijay , Talati Roshan , Patel Priti , Ellison Leonard , Roman Angee , Harrison Jeffrey , Moy James , Naquiallah Dina , Shah Binod , Quintero Orlando , Scott Jake , Jazayeri Yasmin , O'Donnell Andrew , Pathak Divya , Gupta Anita , Chandrasekar N. , Curtis Clifford , White Briana , Dockery Martha , Fortt Tabitha , Fortt Anisa , Jones-Ince Ingrid , McKee Alix , Wilson Jason , Marcelin Jackie , Farlow Brenda , Grady Casey , Richwine Randall , Pazier Penny , Michelson Edward , Watts Susan , Kariyawasam Diluma , Rodriguez Leann , Manresa Ismarys , Achong Angel A. , Garcia Mari C. , Khetpal Sangeeta , Posey Faith , Mahadevan Arvind , Gnoni Martin , Van de Weerd Carla , Lowenkron Jeffrey , Sappington Erica , Roberts Mitchell , Wang Jennifer , Adams Melissa , Ding Xinyi , Co Mary , D'Andrea Mark , Lim Stephen , Swink Wayne , Bozant Emily , Young Madeline , Wilson Michael , Eastin Carly , Cheathem Allyson , Nadeem Ahad , Walters Crystal , Powers-Fletcher Margaret , Brown Douglas , Miller Delia , Mukunzi Sylvere , Manning Brittney , Terry-White Melissa , Crizaldo Maria Christina , Isache Carmen , Bowman Jennifer , Callaghan-Brown Angelique , Martin Debra , Ast Ashley , Duran Brent , Cornejo Ashlie , Archer Allie , Almanzar Maria , Motel Vanessa , Pullen Matt , Anderson Blake , Bhat Neeta , Parra Daniela , Campora Paula , Robinson Matthew , Seithel Michelle , Kendrick Liz , Helming Dyann , Pollock Kelly , Sekikawa Akira , Klawson Emily , Arnold Jonathan , Weiland Nathan , Ostrosky-Zeichner Luis , Patel Bela , Umana Virginia , Nielsen Laura , Grimes Carolyn Z. , Patterson Thomas F. , Tragus Robin , Soileau Bridgette T. , Heath Timothy , Hinjosa Erik , Gutierrez Cesar , Jackson Patrick E.H. , Hallowell Caroline , Haughey Heather M. , Vaidya-Tank Bhavna , Gould Cameron , Goyal Parul , Sommers Sue , Pangburn Haley , Jones Carly , Michalowski Lori , Wortham Brittany , Abbott Rica , Umana Unwana , Alleyne Candace , Witting Britta , Armas Eddie , Perez Landaburo Ramon O. , De La Cruz Michelle , Ballmajo Martha , Alvarez Jorge 
Published: October 2024

ImportanceThe effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain.ObjectiveTo assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19.Design, Setting, and ParticipantsThis 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.InterventionsParticipants were randomized 1:1 to receive montelukast, 10 mg once daily, or matched placebo for 14 days.Main Outcomes and MeasuresThe 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.ResultsAmong 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 RelevanceIn 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 RegistrationClinicalTrials.gov Identifier: NCT04885530