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

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