Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19
Author:
McCarthy Matthew W.1, Naggie Susanna23, Boulware David R.4, Lindsell Christopher J.5, Stewart Thomas G.56, Felker G. Michael23, Jayaweera Dushyantha7, Sulkowski Mark8, Gentile Nina9, Bramante Carolyn4, Singh Upinder10, Dolor Rowena J.23, Ruiz-Unger Juan11, Wilson Sybil2, DeLong Allison2, Remaly April2, Wilder Rhonda2, Collins Sean5, Dunsmore Sarah E.12, Adam Stacey J.13, Thicklin Florence14, Hanna George15, Ginde Adit A.16, Castro Mario17, McTigue Kathleen18, Shenkman Elizabeth19, Hernandez Adrian F.23, Vincent William (Kelly)20, Vincent Raina20, Bianchi Ray20, Premas Jen20, Evelyn Rivera Diana Cordero-Loperena20, Gupta Madhu20, Karawan Greg20, Ziomek Carey20, Arena Joseph20, DeAlmeida Sonaly20, Ramin Soroush20, Nataraj Jaya20, Paasche-Orlow Michael20, Henault Lori20, Waite Katie20, Miller David20, Brounce Ginger20, George-Adebayo Constance20, Adebayo Adeolu20, Wallan Jessica20, Vogel Claudia20, Munoz Sebastian20, Kavtaradze David20, Watson Cassandra20, Singleton David20, Rivon Maria20, Sevier Amanda20, Del Pilar Arnold20, Spangler Amber20, Rao Sohail20, Cantu Luis20, Krishna Arvind20, Evans Kathy20, Falkner Tylene20, Kerr Brandi20, Spees Robert20, Marta Mailyn20, Harrington Amanda20, Frazier Madison20, Vergara Lorraine20, Wilson Jessica20, Burruss Valencia20, Hurst Terri20, Ofotokun Igho20, Bristow Laurel20, Prabhu Rajesh20, Klicka Krystal20, Lightfeather Amber20, James Vicki20, Rogers Marcella20, Parihar Pradeep20, Torress De'Ambra20, Oragwu Chukwuemeka20, Oguego Ngozi20, Pillai Rajesh20, Juma Mustafa20, Ghaly Emad20, Al-Haddadin Dafer20, Ramirez Courtney20, Hassanien Gammal20, Ismail Samah20, Meltzer Andrew20, Moran Seamus20, Brehaut Scott20, Roche Angelina20, Mehta Manisha20, Koppinger Nicole20, Baez Jose20, Pagan Ivone20, Abdelsayed Dallal20, Aziz Mina20, Robinson Philip20, Nguyen Julie20, Pardue Victoria20, Hammons Llisa20, Gonzalez Susan20, Reyes Lionel20, Cienki John20, Jimenez Gisselle20, Cohen Jonathan20, Wong Matthew20, Yuan Ying20, Szeto Jeremy20, Stelmash Lauren20, Amon Arch20, Haight Daniel20, Lamb Deryl20, Harper Amron20, Pyram-Bernard Nancy20, Quintero Arlen20, Adhami Eftim20, Maria Josette20, Paudel Diksha20, Raymond Oksana20, Summers Jeffrey20, Turner Tammy20, Gallegos Sam20, Szwast Elizabeth Ann20, Abdulghani Ahsan20, Vasoya Pravin20, Miller Conrad20, Wiley Hawa20, Klein Tovah20, Castex Julie20, Feliciano Phillip20, Olivo Jacqueline20, Ghaly Marian20, Javed Zainub20, Nawrocki Alexandra20, Vecchiarelli Anthony20, Vigil Nikki20, Cherukuri Vijaya20, Burden Erica20, Linn Dawn20, Fisher Laura20, Patel Vijay20, Patel Praksha20, Patel Yuti20, Ellison Leonard20, Harrison Jeffrey20, Shah Binod20, Shah Sugata20, Shah Upinder20, Donahue Julia20, Jazayeri Yasmin20, Gupta Anita20, Chandrasekar N20, Moritz Beth20, Fortt Tabitha20, Fortt Anisa20, Jones-Ince Ingrid20, McKee Alix20, Schattinger Christy20, Wilson Jason20, Farlow Brenda20, Finlaw Lillian20, Richwine Randall20, Williams Tearani20, Paizer Penny20, Carson Lisa20, Michelson Edward20, Austin Danielle20, Khetpal Sangeeta20, Cantrell Tiffany20, Franklin Drew20, Marshall Karissa20, Mahadevan Arvind20, Rosequist Madelyn20, Gnoni Martin20, Daffner Crystal20, VandeWeerd Carla20, Roberts Mitchell20, D'Andrea Mark20, Lim Stephen20, Swink Wayne20, Powers-Fletcher Margaret20, Mukunzi Sylvere20, Hensley Jamie20, Manning Brittney20, Isache Carmen20, Bowman Jennifer20, Callaghan-Brown Angelique20, Scott Taylor20, Schwasinger-Schmidt Tiffany20, Cornejo Ashlie20, Almanzar Maria20, Ginsburg Letty20, Hajaz Americo20, Robinson Matthew20, Seithel Michelle20, Sekikawa Akira20, Klawson Emily20, Ostrosky Luis20, Umana Virginia20, Patterson Thomas20, Tragus Robin20, Jackson Patrick20, Hallowell Caroline20, Haughey Heather20, Vaidya-Tank Bhavna20, Gould Cameron20, Goyal Parul20, Gatewood Carly20, Williamson John20, Seagle Hannah20, Salsgiver Elizabeth20, Armas Eddie20, Cheng Jhonsai20, Huerta Priscilla20, Garcia-Diaz Julia20, Aamodt David20, Ayers JaMario20, Collins Jess20, Graves John20, Grindstaff James20, Lai Jessica20, Lopez Itzel20, Marlin Jessica20, Merkel Alyssa20, Nwosu Sam20, Obregon Savannah20, Orozco Dirk20, Perez-Torres Yoli20, Prato Nelson20, Ratcliff Colleen20, Rhode Max20, Rothman Russell20, Shirey-Rice Jana20, Vermillion Krista20, Tan Hsi-Nien20, Tregoning Seibert20, Vance Meghan20, Vongsamphanh Amber20, Weir Maria20, Zaleski Nicole20,
Affiliation:
1. Weill Cornell Medicine, New York, New York 2. Duke Clinical Research Institute, School of Medicine, Duke University, Durham, North Carolina 3. Department of Medicine, School of Medicine, Duke University, Durham, North Carolina 4. Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis 5. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee 6. Now with School of Data Science, University of Virginia, Charlottesville 7. Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida 8. Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland 9. Department of Emergency Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 10. Departments of Internal Medicine and Microbiology and Immunology, School of Medicine, Stanford University, Stanford, California 11. Innovation Medical Research Center, Kendall, Florida 12. National Center for Advancing Translational Sciences, Bethesda, Maryland 13. Foundation for the National Institutes of Health, Bethesda, Maryland 14. Stakeholder Advisory Committee, Pittsburgh, Pennsylvania 15. Biomedical Advanced Research and Development Authority, Washington, DC 16. Department of Emergency Medicine, University of Colorado, Denver 17. Division of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, University of Missouri, Kansas City, Kansas 18. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 19. Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville 20. for the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators
Abstract
ImportanceThe effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear.ObjectiveTo evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US.Design, Setting, and ParticipantsThe ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) platform randomized clinical trial was designed to test repurposed medications in outpatients with mild to moderate COVID-19. A total of 1288 participants aged 30 years or older with test-confirmed SARS-CoV-2 infection and experiencing 2 or more symptoms of acute COVID-19 for 7 days or less were enrolled between August 6, 2021, and May 27, 2022, at 91 sites in the US.InterventionsParticipants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo.Main Outcomes and MeasuresThe primary outcome was time to sustained recovery (defined as the third day of 3 consecutive days without symptoms). There were 7 secondary outcomes, including a composite outcome of hospitalization, urgent care visit, emergency department visit, or death through day 28.ResultsAmong 1331 participants who were randomized (median age, 47 years [IQR, 38-57 years]; 57% were women; and 67% reported receiving ≥2 doses of a SARS-CoV-2 vaccine), 1288 completed the trial (674 in the fluvoxamine group and 614 in the placebo group). The median time to sustained recovery was 12 days (IQR, 11-14 days) in the fluvoxamine group and 13 days (IQR, 12-13 days) in the placebo group (hazard ratio [HR], 0.96 [95% credible interval, 0.86-1.06], posterior P = .21 for the probability of benefit [determined by an HR >1]). For the composite outcome, 26 participants (3.9%) in the fluvoxamine group were hospitalized, had an urgent care visit, had an emergency department visit, or died compared with 23 participants (3.8%) in the placebo group (HR, 1.1 [95% credible interval, 0.5-1.8], posterior P = .35 for the probability of benefit [determined by an HR <1]). One participant in the fluvoxamine group and 2 participants in the placebo group were hospitalized; no deaths occurred in either group. Adverse events were uncommon in both groups.Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with 50 mg of fluvoxamine twice daily for 10 days, compared with placebo, did not improve time to sustained recovery. These findings do not support the use of fluvoxamine at this dose and duration in patients with mild to moderate COVID-19.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530
Publisher
American Medical Association (AMA)
Cited by
45 articles.
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