Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19
Authors: McCarthy Matthew W. , Naggie Susanna , Boulware David R. , Lindsell Christopher J. , Stewart Thomas G. , Felker G. Michael , Jayaweera Dushyantha , Sulkowski Mark , Gentile Nina , Bramante Carolyn , Singh Upinder , Dolor Rowena J. , Ruiz-Unger Juan , Wilson Sybil , DeLong Allison , Remaly April , Wilder Rhonda , Collins Sean , Dunsmore Sarah E. , Adam Stacey J. , Thicklin Florence , Hanna George , Ginde Adit A. , Castro Mario , McTigue Kathleen , Shenkman Elizabeth , Hernandez Adrian F. ,   Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators, Vincent William (Kelly) , Vincent Raina , Bianchi Ray , Premas Jen , Evelyn Rivera Diana Cordero-Loperena , Gupta Madhu , Karawan Greg , Ziomek Carey , Arena Joseph , DeAlmeida Sonaly , Ramin Soroush , Nataraj Jaya , Paasche-Orlow Michael , Henault Lori , Waite Katie , Miller David , Brounce Ginger , George-Adebayo Constance , Adebayo Adeolu , Wallan Jessica , Vogel Claudia , Munoz Sebastian , Kavtaradze David , Watson Cassandra , Singleton David , Rivon Maria , Sevier Amanda , Del Pilar Arnold , Spangler Amber , Rao Sohail , Cantu Luis , Krishna Arvind , Evans Kathy , Falkner Tylene , Kerr Brandi , Spees Robert , Marta Mailyn , Harrington Amanda , Frazier Madison , Vergara Lorraine , Wilson Jessica , Burruss Valencia , Hurst Terri , Ofotokun Igho , Bristow Laurel , Prabhu Rajesh , Klicka Krystal , Lightfeather Amber , James Vicki , Rogers Marcella , Parihar Pradeep , Torress De'Ambra , Oragwu Chukwuemeka , Oguego Ngozi , Pillai Rajesh , Juma Mustafa , Ghaly Emad , Al-Haddadin Dafer , Ramirez Courtney , Hassanien Gammal , Ismail Samah , Meltzer Andrew , Moran Seamus , Brehaut Scott , Roche Angelina , Mehta Manisha , Koppinger Nicole , Baez Jose , Pagan Ivone , Abdelsayed Dallal , Aziz Mina , Robinson Philip , Nguyen Julie , Pardue Victoria , Hammons Llisa , Gonzalez Susan , Reyes Lionel , Cienki John , Jimenez Gisselle , Cohen Jonathan , Wong Matthew , Yuan Ying , Szeto Jeremy , Stelmash Lauren , Amon Arch , Haight Daniel , Lamb Deryl , Harper Amron , Pyram-Bernard Nancy , Quintero Arlen , Adhami Eftim , Maria Josette , Paudel Diksha , Raymond Oksana , Summers Jeffrey , Turner Tammy , Gallegos Sam , Szwast Elizabeth Ann , Abdulghani Ahsan , Vasoya Pravin , Miller Conrad , Wiley Hawa , Klein Tovah , Castex Julie , Feliciano Phillip , Olivo Jacqueline , Ghaly Marian , Javed Zainub , Nawrocki Alexandra , Vecchiarelli Anthony , Vigil Nikki , Cherukuri Vijaya , Burden Erica , Linn Dawn , Fisher Laura , Patel Vijay , Patel Praksha , Patel Yuti , Ellison Leonard , Harrison Jeffrey , Shah Binod , Shah Sugata , Shah Upinder , Donahue Julia , Jazayeri Yasmin , Gupta Anita , Chandrasekar N , Moritz Beth , Fortt Tabitha , Fortt Anisa , Jones-Ince Ingrid , McKee Alix , Schattinger Christy , Wilson Jason , Farlow Brenda , Finlaw Lillian , Richwine Randall , Williams Tearani , Paizer Penny , Carson Lisa , Michelson Edward , Austin Danielle , Khetpal Sangeeta , Cantrell Tiffany , Franklin Drew , Marshall Karissa , Mahadevan Arvind , Rosequist Madelyn , Gnoni Martin , Daffner Crystal , VandeWeerd Carla , Roberts Mitchell , D'Andrea Mark , Lim Stephen , Swink Wayne , Powers-Fletcher Margaret , Mukunzi Sylvere , Hensley Jamie , Manning Brittney , Isache Carmen , Bowman Jennifer , Callaghan-Brown Angelique , Scott Taylor , Schwasinger-Schmidt Tiffany , Cornejo Ashlie , Almanzar Maria , Ginsburg Letty , Hajaz Americo , Robinson Matthew , Seithel Michelle , Sekikawa Akira , Klawson Emily , Ostrosky Luis , Umana Virginia , Patterson Thomas , Tragus Robin , Jackson Patrick , Hallowell Caroline , Haughey Heather , Vaidya-Tank Bhavna , Gould Cameron , Goyal Parul , Gatewood Carly , Williamson John , Seagle Hannah , Salsgiver Elizabeth , Armas Eddie , Cheng Jhonsai , Huerta Priscilla , Garcia-Diaz Julia , Aamodt David , Ayers JaMario , Collins Jess , Graves John , Grindstaff James , Lai Jessica , Lopez Itzel , Marlin Jessica , Merkel Alyssa , Nwosu Sam , Obregon Savannah , Orozco Dirk , Perez-Torres Yoli , Prato Nelson , Ratcliff Colleen , Rhode Max , Rothman Russell , Shirey-Rice Jana , Vermillion Krista , Tan Hsi-Nien , Tregoning Seibert , Vance Meghan , Vongsamphanh Amber , Weir Maria , Zaleski Nicole 
Published: January 2023

Importance

The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear.

Objective

To 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 Participants

The 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.

Interventions

Participants were randomized to receive 50 mg of fluvoxamine twice daily for 10 days or placebo.

Main Outcomes and Measures

The 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.

Results

Among 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 &amp;gt;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 &amp;lt;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 Relevance

Among 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 Registration

ClinicalTrials.gov Identifier: NCT04885530