Article
Author: Martin, Debra ; Samir, Yehia ; Gentile, Nina ; Burns, Andrea ; Miller, Delia ; Meltzer, Andrew ; Quintero, Arlen ; Grady, Casey ; Jayaweera, Dushyantha ; Adam, Stacey J. ; Powers-Fletcher, Margaret ; Seithel, Michelle ; Rodriguez, Leann ; Pagan, Ivone ; Zamora, Yadira ; Armas, Eddie ; Carrillo, Giovanni ; Chopp, Julie ; Orozco, Dirk ; Munoz, Sebastian ; Sevier, Marcus ; Randle, Desmon ; Ramin, Soroush ; Oragwu, Chukwuemeka ; Swink, Wayne ; Liao, Vicky ; Mukunzi, Sylvere ; Watson, Casandra ; Griffin, Alvin ; Maldonado, Maria ; McTigue, Kathleen ; Roche, Angelina ; Rivera, Evelyn ; Vecchiarelli, Anthony ; Lindsell, Christopher J. ; Woods, Ashley ; Kariyawasam, Diluma ; Juma, Mustafa ; Posey, Faith ; Heidish, Ryan S. ; Martin, Raykel ; Zapatero, Jose ; Ballmajo, Martha ; Love, Nicole ; Milstone, Aaron ; Lightfeather, Amber ; De La Cruz, Michelle ; Adams, Melissa ; Chan, Austin ; Dixon, Sheri ; Lamb, Deryl ; James, Vickie ; Chen, July ; Bozant, Emily ; Manning, Brittney ; Mehta, Manisha ; Shenkman, Elizabeth ; Cardona, Orlando Quintero ; Beauchaine, Meaghan ; Rebolledo, Paulina A. ; Ast, Ashley ; Michal, Marian ; Rothman, Russell L. ; Wells, Kadie ; Tragus, Robin ; Lima, Santia ; Lopez, Itzel ; Sexton, Cedar ; Thicklin, Florence ; Szeto, Jeremy ; Cordero-Loperena, Diana ; Robinson, Matthew ; Naggie, Susanna ; Garcia del Sol, Idania T. ; Marlin, Jessica ; Cornejo, Ashlie ; Curtis, Clifford ; Gabriel, Ahab ; Wallan, Jessica ; Harrington, Amanda ; Soileau, Bridgette T. ; Jones, Carly ; Talati, Roshan ; Herbert, Alicia ; Averett, Amaya ; Alleyne, Candace ; Abbott, Rica ; Chi, Wei Ning ; Dockery, Samantha ; Weir, Maria ; Vasquez, Michelle ; Manresa, Ismarys ; Jazayeri, Yasmin ; Alicic, Radica ; Grindstaff, James ; Vogel, Claudia ; Abdelsayed, Dallal ; Nwosu, Sam ; Nowell, Erin ; Rogers, Marcella ; Collins, Jess ; Daugherty, Heidi ; Farlow, Brenda ; Cantu, Luis ; Harrell, Frank ; Koppinger, Nicole ; Roberts, Mitchell ; Gupta, Anita ; Southwell, Alexis ; DeComarmond, Mathias ; Morris, Michael ; Szwast, Elizabeth ; Arnold, Jonathan ; Cohen, Jonathan ; Maria, Josette ; Miller, David ; Oyelakin, Martina ; Motel, Vanessa ; Paudel, Diksha ; Marta, Mailyn ; Smith, Jacob ; Merkel, Alyssa ; Gaytan-Alvarez, Diana ; Patel, Yuti ; Panaccione, Ebony ; Jacques, Genice ; Prato, Nelson ; Patel, Vijay ; Rowland, Teddy ; Aziz, Mina ; Wang, Jennifer ; Samraj, Joshua ; Wills, Walter ; Hassanien, Gammal ; McCarthy, Matthew W. ; Oguego, Ngozi ; Wilson, Jason ; Seagle, Hannah ; Premas, Jen ; Umana, Unwana ; Obregon, Savannah ; Fortt, Anisa ; Khizer, Saadia ; Castex, Julie ; Smith, Veronica E. ; Barbera, Andrew ; Olofintuyi, Anthony ; Bianchi, Ray ; Vaidya-Tank, Bhavna ; Adhami, Eftim ; Korzekwinski, Kayla ; Adebayo, Adeolu ; Samraj, Jackelyn ; Parihar, Pradeep ; Ginde, Adit A. ; Ramirez, Ana Maria ; Bhat, Neeta ; Pyram-Bernard, Nancy ; Vergara, Lorraine ; Olivo, Jacqueline ; Moy, James ; Feliciano, Phillip ; Rao, Sohail ; Ding, Xinyi ; Stout, Elmer ; Klicka, Krystal ; Parra, Daniela ; Robbs, Lindsey ; Dunsmore, Sarah E. ; Gupta, Madhu ; Goyal, Parul ; Del Pilar, Arnold ; Chandrasekar, N ; Harper, Amron ; Urbat, Carissa ; McKee, Alix ; Dedier, Julien ; Vance, Meghan ; Cherukuri, Vijaya ; Patterson, Thomas F. ; Gallegos, Christopher ; Lozinski, Grace ; Naquiallah, Dina ; Ghaly, Emad ; Manis, Elizabeth ; Garcia, Mari ; Graves, John ; Pathak, Divya ; Gould, Cameron ; Ruiz-Unger, Juan ; Marcus, Joseph ; Cooper, Ann ; Lindblom, Kelly ; Pazier, Penny ; Achong, Angel ; Hurst, Terri ; Hallowell, Carolina ; DeAlmeida, Sonaly ; Fortt, Tabitha ; Tan, Hsi-nien ; Richwine, Randall ; Vincent, Raina ; D'Andrea, Mark ; Singleton, David ; Archer, Allie ; McAdams, M. Patricia ; Linn, Dawn ; Collins, Sean ; Ostrosky-Zeichner, Luis ; Michelson, Edward ; Vasoya, Pravin ; Harrison, Jeffrey ; Baez, Jose ; Khetpal, Sangeeta ; Ellison, Leonard ; Vermillion, Krista ; Bacallao, Navila ; Umana, Virginia ; Spees, Robert ; Watts, Susan ; Aamodt, David ; Ward, Mark ; Hicks, Maya ; Shah, Nirav ; Morton-Jost, Melissa ; Sekikawa, Akira ; Bugajski, Andrew ; Gao, Yue ; Mankowski, Kalley ; Stone, Allegra ; Jackson, Patrick E.H. ; Fraser, Ryan ; Sommers, Sue ; Nielsen, Laura ; White, Briana ; Robinson, Philip ; Perez Landabur, Ramon O. ; Sappington, Erica ; Shirey-Rice, Jana ; Ofotokun, Igho ; Williamson, John ; Evans, Kathy ; Krishna, Arvind ; Rohde, Max ; Quintero, Orlando ; Schwasinger-Schmidt, Tiffany ; Felker, G. Michael ; Yuan, Ying ; Fisher, Laura ; Karawan, Greg ; Li, Jenny ; Pickell, Nicholas ; Sulkowski, Mark ; Pangburn, Haley ; Isache, Carmen ; Gamboa Jackman, Jennifer ; Rivon, Maria ; Jordan, Jackie ; Scott, Jake ; Harding, Tina ; Mourad, Ahmad ; Waite, Katherine ; Luis Garcia, Jose ; Heavlin, Heather ; Slandzicki, Alex ; Jacklin, Kellcee ; Clement, Julie ; Shahamatdar, Soroush ; Lenert, Leslie A. ; Patel, Priti ; Reyes, Lionel ; O’Donnell, Andrew ; Brehaut, Scott ; Kavtaradze, David ; Lai, Jessica ; Mattox, Bonnie ; Prabhu, Rajesh ; Shah, Binod ; DeLong, Allison ; Castro, Mario ; Sloan, Olivia ; Miller, Conrad ; Stelmash, Lauren ; Haughey, Heather M. ; Sheets, Michelle ; Garcia del Sol, Idania ; Jones-Ince, Ingrid ; Williams, Tearani ; Arena, Joseph ; Lim, Stephen ; Nguyen, Julie ; Lambert, Allison A. ; Weeks, Katherine ; Brown, Linley ; Almanzar, Maria ; Raymond, Oksana ; Vasbinder, Alma ; Bramante, Carolyn T. ; Mahadevan, Arvind ; Boulware, David R. ; Singh, Upinder ; Crow, Mathew ; Nataraj, Jaya ; Campora, Paula ; Pardue, Victoria ; Roman, Angee ; Summers, Jeffrey ; Torress, De'Ambra ; Brounce, Ginger ; Adeyemi, Oluwadamilola ; Flys, Tamara ; Duran, Brent ; Kerr, Brandi ; Ronan, Theresa ; Pullen, Matthew ; George-Adebayo, Constance ; Wiley, Hawa ; Wilder, Rhonda ; Ismail, Samah ; Grimes, Carolyn Z. ; Turner, Tammy ; Gutierrez, Anya ; Morales Castillo, Ledular ; Dockery, Martha ; Vincent, William (Kelly) ; Baxter, Joni ; Adkins, Rodney ; Stewart, Thomas G. ; Cienki, John ; Callaghan-Brown, Angelique ; Pillai, Rajesh ; Vail, Julia ; Amon, Arch ; Abdulghani, Ahsan ; Okulicz, Jason ; Hanna, George J. ; Dolor, Rowena ; Bowman, Jennifer ; Hernandez, Adrian F. ; Mamon, Angela ; Prieto, Sabrina ; Zhang, Cecilia ; VandeWeerd, Carla ; Williamson, John C. ; Spangler, Amber ; Burruss, Valencia ; Griffin, Merischia ; Gnoni, Martin ; Klawson, Emily
ImportanceThe effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.ObjectiveTo assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.Design, Setting, and ParticipantsThe ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less.InterventionsParticipants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607).Main Outcomes and MeasuresThe 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-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28.ResultsAmong 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths.Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530