Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19
Author:
Naggie Susanna12, Boulware David R.3, Lindsell Christopher J.4, Stewart Thomas G.4, Gentile Nina5, Collins Sean4, McCarthy Matthew William6, Jayaweera Dushyantha7, Castro Mario8, Sulkowski Mark9, McTigue Kathleen10, Thicklin Florence11, Felker G. Michael12, Ginde Adit A.12, Bramante Carolyn T.3, Slandzicki Alex J.13, Gabriel Ahab14, Shah Nirav S.15, Lenert Leslie A.16, Dunsmore Sarah E.17, Adam Stacey J.18, DeLong Allison1, Hanna George19, Remaly April1, Wilder Rhonda1, Wilson Sybil1, Shenkman Elizabeth20, Hernandez Adrian F.12, Vincent William (Kelly)21, Vincent Raina21, Bianchi Ray21, Premas Jen21, Cordero-Loperena Diana21, Rivera Evelyn21, Gupta Madhu21, Karawan Greg21, Ziomek Carey21, Arena Joseph21, DeAlmeida Sonaly21, Ramin Soroush21, Nataraj Jaya21, Paasche-Orlow Michael21, Henault Lori21, Waite Katie21, Miller David21, Brounce Ginger21, George-Adebayo Constance21, Adebayo Adeolu21, Wallan Jessica21, Slandzicki Alex21, Vogel Claudia21, Munoz Sebastian21, Kavtaradze David21, Watson Cassandra21, Singleton David21, Rivon Maria21, Sevier Amanda21, Del Pilar Arnold21, Spangler Amber21, Rao Sohail21, Cantu Luis21, Krishna Arvind21, Evans Kathy21, Falkner Tylene21, Kerr Brandi21, Spees Robert21, Marta Mailyn21, Felker G. Michael21, Harrington Amanda21, Dolor Rowena21, Frazier Madison21, Vergara Lorraine21, Wilson Jessica21, Burruss Valencia21, Hurst Terri21, Ofotokun Igho21, Bristow Laurel21, Prabhu Rajesh21, Klicka Krystal21, Lightfeather Amber21, James Vicki21, Rogers Marcella21, Parihar Pradeep21, Torress De'Ambra21, Oragwu Chukwuemeka21, Oguego Ngozi21, Pillai Rajesh21, Juma Mustafa21, Gabriel Ahab21, Ghaly Emad21, Al-Haddadin Dafer21, Ramirez Courtney21, Hassanien Gammal21, Ismail Samah21, Meltzer Andrew21, Moran Seamus21, Brehaut Scott21, Roche Angelina21, Mehta Manisha21, Koppinger Nicole21, Baez Jose21, Pagan Ivone21, Abdelsayed Dallal21, Aziz Mina21, Robinson Philip21, Nguyen Julie21, Pardue Victoria21, Hammons Llisa21, Ruiz-Unger Juan21, Gonzalez Susan21, Reyes Lionel21, Cienki John21, Jimenez Gisselle21, Cohen Jonathan21, Wong Matthew21, Yuan Ying21, Szeto Jeremy21, Sulkowski Mark21, Stelmash Lauren21, Amon Arch21, Haight Daniel21, Lamb Deryl21, Harper Amron21, Pyram-Bernard Nancy21, Quintero Arlen21, Adhami Eftim21, Maria Josette21, Paudel Diksha21, Raymond Oksana21, Summers Jeffrey21, Turner Tammy21, Lenert Leslie21, Gallegos Sam21, Szwast Elizabeth Ann21, Abdulghani Ahsan21, Vasoya Pravin21, Miller Conrad21, Wiley Hawa21, Shah Nirav21, Klein Tovah21, Castex Julie21, Feliciano Phillip21, Olivo Jacqueline21, Ghaly Marian21, Javed Zainub21, Nawrocki Alexandra21, Vecchiarelli Anthony21, Vigil Nikki21, Cherukuri Vijaya21, Burden Erica21, Linn Dawn21, Fisher Laura21, Patel Vijay21, Patel Praksha21, Patel Yuti21, Ellison Leonard21, Harrison Jeffrey21, Shah Binod21, Shah Sugata21, Shah Upinder21, Donahue Julia21, Jazayeri Yasmin21, Gupta Anita21, Chandrasekar N21, Moritz Beth21, Fortt Tabitha21, Fortt Anisa21, Jones-Ince Ingrid21, McKee Alix21, Schattinger Christy21, Wilson Jason21, Farlow Brenda21, Gentile Nina21, Finlaw Lillian21, Richwine Randall21, Williams Tearani21, Paizer Penny21, Carson Lisa21, Michelson Edward21, Austin Danielle21, Khetpal Sangeeta21, Cantrell Tiffany21, Franklin Drew21, Marshall Karissa21, Mahadevan Arvind21, Rosequist Madelyn21, Gnoni Martin21, Daffner Crystal21, VandeWeerd Carla21, Roberts Mitchell21, D'Andrea Mark21, Lim Stephen21, Swink Wayne21, Powers-Fletcher Margaret21, Mukunzi Sylvere21, Shenkman Elizabeth21, Hensley Jamie21, Manning Brittney21, Isache Carmen21, Bowman Jennifer21, Callaghan-Brown Angelique21, Scott Taylor21, Schwasinger-Schmidt Tiffany21, Cornejo Ashlie21, Jayaweera Dushyantha21, Almanzar Maria21, Ginsburg Letty21, Hajaz Americo21, Bramante Carolyn21, Robinson Matthew21, Seithel Michelle21, Sekikawa Akira21, Klawson Emily21, Ostrosky Luis21, Umana Virginia21, Patterson Thomas21, Tragus Robin21, Jackson Patrick21, Hallowell Caroline21, Haughey Heather21, Vaidya-Tank Bhavna21, Gould Cameron21, Goyal Parul21, Gatewood Carly21, Williamson John21, Seagle Hannah21, McCarthy Matthew21, Salsgiver Elizabeth21, Armas Eddie21, Cheng Jhonsai21, Huerta Priscilla21, Garcia-Diaz Julia21, Aamodt David21, Ayers JaMario21, Collins Jess21, Graves John21, Grindstaff James21, Harrell Frank21, Lai Jessica21, Lopez Itzel21, Marlin Jessica21, Merkel Alyssa21, Nwosu Sam21, Obregon Savannah21, Orozco Dirk21, Perez-Torres Yoli21, Prato Nelson21, Ratcliff Colleen21, Rhode Max21, Rothman Russell21, Shirey-Rice Jana21, Vermillion Krista21, Tan Hsi-Nien21, Tregoning Seibert21, Vance Meghan21, Vongsamphanh Amber21, Weir Maria21, Zaleski Nicole21,
Affiliation:
1. Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina 2. Department of Medicine, Duke University School of Medicine, Durham, North Carolina 3. Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis 4. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee 5. Department of Emergency Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 6. Department of Medicine, Weill Cornell Medicine, New York, New York 7. Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida 8. Division of Pulmonary, Critical Care and Sleep Medicine, University of Missouri-Kansas City School of Medicine, Kansas City, Kansas 9. Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland 10. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 11. Stakeholder Advisory Committee, Pittsburgh, Pennsylvania 12. Department of Emergency Medicine, University of Colorado Denver-Anschutz, Denver 13. Clinical Trials Center of Middle Tennessee, Franklin 14. Focus Clinical Research Solutions, Charlotte, North Carolina 15. NorthShore University HealthSystem, Evanston, Illinois 16. Department of Medicine, Medical University of South Carolina, Charleston 17. National Center for Advancing Translational Sciences, Bethesda, Maryland 18. Foundation for the National Institutes of Health, Bethesda, Maryland 19. Biomedical Advanced Research and Development Authority, Washington, DC 20. Department of Health Outcomes & Biomedical Informatics, College of Medicine, University of Florida, Gainesville 21. for the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-6) Study Group and Investigators
Abstract
ImportanceThe effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown.ObjectiveTo evaluate the efficacy of ivermectin, 400 μg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19.Design, Setting, and ParticipantsACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 91 sites in the US.InterventionsParticipants were randomized to receive ivermectin, 400 μg/kg (n = 817), daily for 3 days or placebo (n = 774).Main Outcomes and MeasuresTime to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28.ResultsAmong 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]).Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19.Trial RegistrationClinicalTrials.gov Identifier: NCT04885530
Publisher
American Medical Association (AMA)
Cited by
48 articles.
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