Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19
Author:
Stewart Thomas G.1, Rebolledo Paulina A.2, Mourad Ahmad34, Lindsell Christopher J.3, Boulware David R.5, McCarthy Matthew W.6, Thicklin Florence7, Garcia del Sol Idania T.8, Bramante Carolyn T.5, Lenert Leslie A.9, Lim Stephen10, Williamson John C.11, Cardona Orlando Quintero12, Scott Jake12, Schwasinger-Schmidt Tiffany13, Ginde Adit A.14, Castro Mario15, Jayaweera Dushyantha16, Sulkowski Mark17, Gentile Nina18, McTigue Kathleen19, Felker G. Michael34, DeLong Allison4, Wilder Rhonda4, Rothman Russell L.20, Collins Sean2021, Dunsmore Sarah E.22, Adam Stacey J.23, Hanna George J.24, Shenkman Elizabeth25, Hernandez Adrian F.34, Naggie Susanna34, Fraser Ryan26, Ward Mark26, Gamboa Jackman Jennifer26, McAdams M. Patricia26, Vail Julia26, Korzekwinski Kayla26, Oyelakin Martina26, Chopp Julie26, Randle Desmon26, Dockery Samantha26, Adkins Rodney26, Crow Mathew26, Nowell Erin26, Wells Kadie26, Herbert Alicia26, Stone Allegra26, Heavlin Heather26, Brown Linley26, Harding Tina26, Harrington Amanda26, Beauchaine Meaghan26, Lindblom Kelly26, Burns Andrea26, Aamodt David26, Collins Jess26, Dixon Sheri26, Gao Yue26, Graves John26, Grindstaff James26, Harrell Frank26, Lai Jessica26, Liao Vicky26, Lopez Itzel26, Manis Elizabeth26, Mankowski Kalley26, Marlin Jessica26, Merkel Alyssa26, Nwosu Sam26, Obregon Savannah26, Orozco Dirk26, Prato Nelson26, Rohde Max26, Shirey-Rice Jana26, Vermillion Krista26, Smith Jacob26, Tan Hsi-nien26, Vance Meghan26, Weir Maria26, Vincent William (Kelly)26, Vincent Raina26, Bianchi Ray26, Premas Jen26, Cordero-Loperena Diana26, Rivera Evelyn26, Gupta Madhu26, Karawan Greg26, Arena Joseph26, DeAlmeida Sonaly26, Ramin Soroush26, Nataraj Jaya26, Dedier Julien26, Ramirez Ana Maria26, Waite Katherine26, Okulicz Jason26, Marcus Joseph26, Southwell Alexis26, Jacques Genice26, Sexton Cedar26, Miller David26, Brounce Ginger26, George-Adebayo Constance26, Adebayo Adeolu26, Zapatero Jose26, Clement Julie26, Ronan Theresa26, Woods Ashley26, Gallegos Christopher26, Flys Tamara26, Sloan Olivia26, Olofintuyi Anthony26, Samraj Joshua26, Samraj Jackelyn26, Vasbinder Alma26, Averett Amaya26, Slandzicki Alex26, Milstone Aaron26, Wallan Jessica26, Robbs Lindsey26, Vogel Claudia26, Munoz Sebastian26, Kavtaradze David26, Watson Casandra26, Singleton David26, Sevier Marcus26, Rivon Maria26, Del Pilar Arnold26, Spangler Amber26, Rao Sohail26, Cantu Luis26, Krishna Arvind26, Daugherty Heidi26, Kerr Brandi26, Evans Kathy26, Spees Robert26, Marta Mailyn26, Dolor Rowena26, Vergara Lorraine26, Jordan Jackie26, Burruss Valencia26, Hurst Terri26, Ofotokun Igho26, Rebolledo Paulina A.26, Zhang Cecilia26, Smith Veronica E.26, Prabhu Rajesh26, Klicka Krystal26, Lightfeather Amber26, James Vickie26, Rogers Marcella26, Parihar Pradeep26, Torress De'Ambra26, Oragwu Chukwuemeka26, Oguego Ngozi26, Pillai Rajesh26, Juma Mustafa26, Gabriel Ahab26, Ghaly Emad26, Michal Marian26, Vasquez Michelle26, Mamon Angela26, Sheets Michelle26, Hassanien Gammal26, Ismail Samah26, Samir Yehia26, Meltzer Andrew26, Shahamatdar Soroush26, Heidish Ryan S.26, Brehaut Scott26, Roche Angelina26, Mehta Manisha26, Koppinger Nicole26, Baez Jose26, Pagan Ivone26, Abdelsayed Dallal26, Aziz Mina26, Robinson Philip26, Lozinski Grace26, Nguyen Julie26, Griffin Alvin26, Morris Michael26, Love Nicole26, Mattox Bonnie26, Martin Raykel26, Pardue Victoria26, Rowland Teddy26, Ruiz-Unger Juan26, Reyes Lionel26, Zamora Yadira26, Bacallao Navila26, Cienki John26, Cohen Jonathan26, Yuan Ying26, Li Jenny26, Szeto Jeremy26, Sulkowski Mark26, Stelmash Lauren26, Garcia del Sol Idania26, Morales Castillo Ledular26, Gutierrez Anya26, Prieto Sabrina26, Amon Arch26, Barbera Andrew26, Bugajski Andrew26, Wills Walter26, Jacklin Kellcee26, Lamb Deryl26, Harper Amron26, Stout Elmer26, Weeks Katherine26, Griffin Merischia26, Pyram-Bernard Nancy26, Quintero Arlen26, Adhami Eftim26, Carrillo Giovanni26, Maria Josette26, Paudel Diksha26, Raymond Oksana26, Summers Jeffrey26, Turner Tammy26, Panaccione Ebony26, Szwast Elizabeth26, Abdulghani Ahsan26, Vasoya Pravin26, Miller Conrad26, Wiley Hawa26, Chan Austin26, Khizer Saadia26, Shah Nirav26, Adeyemi Oluwadamilola26, Chi Wei Ning26, Chen July26, Morton-Jost Melissa26, Castex Julie26, Feliciano Phillip26, Olivo Jacqueline26, Maldonado Maria26, Vecchiarelli Anthony26, Gaytan-Alvarez Diana26, Cherukuri Vijaya26, Lima Santia26, Alicic Radica26, Lambert Allison A.26, Urbat Carissa26, Baxter Joni26, Cooper Ann26, Linn Dawn26, Fisher Laura26, Patel Vijay26, Patel Yuti26, Talati Roshan26, Patel Priti26, Ellison Leonard26, Roman Angee26, Harrison Jeffrey26, Moy James26, Naquiallah Dina26, Shah Binod26, Singh Upinder26, Jazayeri Yasmin26, O’Donnell Andrew26, Quintero Orlando26, Pathak Divya26, Gupta Anita26, Chandrasekar N26, Curtis Clifford26, White Briana26, Dockery Martha26, Hicks Maya26, Fortt Tabitha26, Fortt Anisa26, Jones-Ince Ingrid26, McKee Alix26, Wilson Jason26, Farlow Brenda26, Gentile Nina26, Grady Casey26, Richwine Randall26, Williams Tearani26, Pazier Penny26, Michelson Edward26, Watts Susan26, Kariyawasam Diluma26, Rodriguez Leann26, Luis Garcia Jose26, Manresa Ismarys26, Achong Angel26, Garcia Mari26, Khetpal Sangeeta26, Posey Faith26, Mahadevan Arvind26, Gnoni Martin26, VandeWeerd Carla26, Sappington Erica26, Roberts Mitchell26, Wang Jennifer26, Adams Melissa26, Ding Xinyi26, D'Andrea Mark26, Lim Stephen26, Swink Wayne26, Bozant Emily26, Powers-Fletcher Margaret26, Miller Delia26, Mukunzi Sylvere26, Manning Brittney26, Isache Carmen26, Bowman Jennifer26, Callaghan-Brown Angelique26, Martin Debra26, Ast Ashley26, Duran Brent26, Cornejo Ashlie26, Archer Allie26, Jayaweera Dushyantha26, Almanzar Maria26, Motel Vanessa26, Bhat Neeta26, Parra Daniela26, Pullen Matthew26, Campora Paula26, Robinson Matthew26, Seithel Michelle26, Sekikawa Akira26, Klawson Emily26, Arnold Jonathan26, Ostrosky-Zeichner Luis26, Umana Virginia26, Nielsen Laura26, Grimes Carolyn Z.26, Patterson Thomas F.26, Tragus Robin26, Soileau Bridgette T.26, Jackson Patrick E.H.26, Hallowell Carolina26, Haughey Heather M.26, Vaidya-Tank Bhavna26, Gould Cameron26, Goyal Parul26, Sommers Sue26, Pangburn Haley26, Jones Carly26, Williamson John26, Abbott Rica26, Seagle Hannah26, DeComarmond Mathias26, Pickell Nicholas26, Umana Unwana26, Alleyne Candace26, Armas Eddie26, Perez Landabur Ramon O.26, De La Cruz Michelle26, Ballmajo Martha26,
Affiliation:
1. School of Data Science, University of Virginia, Charlottesville 2. Department of Medicine and Global Health, Division of Infectious Diseases, Emory University School of Medicine and Rollins School of Public Health, Atlanta, Georgia 3. Department of Medicine, Duke University School of Medicine, Durham, North Carolina 4. Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina 5. University of Minnesota Medical School, General Internal Medicine, Minneapolis 6. Weill Cornell Medicine, New York, New York 7. Stakeholder Advisory Committee, Pittsburgh, Pennsylvania 8. L&A Morales Healthcare, Inc, Hialeah, Florida 9. Medical University of South Carolina, Charleston 10. Louisiana State University Health Sciences Center New Orleans, University Medical Center New Orleans, New Orleans 11. Wake Forest University School of Medicine, Department of Internal Medicine, Section on Infectious Diseases, Winston-Salem, North Carolina 12. Stanford University School of Medicine, Department of Medicine, Infectious Diseases and Geographic Medicine Division, Stanford, California 13. University of Kansas School of Medicine-Wichita, Center for Clinical Research, Wichita 14. University of Colorado School of Medicine, Aurora 15. Division of Pulmonary, Critical Care and Sleep Medicine, University of Missouri-Kansas City School of Medicine, Kansas City 16. Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida 17. Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland 18. Department of Emergency Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 19. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 20. Vanderbilt University Medical Center, Nashville, Tennessee 21. Veterans Affairs Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Nashville 22. National Center for Advancing Translational Sciences, Bethesda, Maryland 23. Foundation for the National Institutes of Health, Bethesda, Maryland 24. Biomedical Advanced Research and Development Authority, Washington, DC 25. Department of Health Outcomes & Biomedical Informatics, College of Medicine, University of Florida, Gainesville 26. for the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators
Abstract
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
Publisher
American Medical Association (AMA)
Cited by
2 articles.
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