Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19
Author:
Naggie Susanna12, Boulware David R.3, Lindsell Christopher J.4, Stewart Thomas G.5, Slandzicki Alex J.6, Lim Stephen C.7, Cohen Jonathan8, Kavtaradze David9, Amon Arch P.10, Gabriel Ahab11, Gentile Nina12, Felker G. Michael12, Jayaweera Dushyantha13, McCarthy Matthew W.14, Sulkowski Mark15, Rothman Russell L.4, Wilson Sybil1, DeLong Allison1, Remaly April1, Wilder Rhonda1, Collins Sean416, Dunsmore Sarah E.17, Adam Stacey J.18, Thicklin Florence19, Hanna George J.20, Ginde Adit A.21, Castro Mario22, McTigue Kathleen23, Shenkman Elizabeth24, Hernandez Adrian F.12, Vincent William (Kelly)25, Vincent Raina25, Bianchi Ray25, Premas Jen25, Cordero-Loperena Diana25, Rivera Evelyn25, Gupta Madhu25, Karawan Greg25, Ziomek Carey25, Arena Joseph25, DeAlmeida Sonaly25, Ramin Soroush25, Nataraj Jaya25, Paasche-Orlow Michael25, Henault Lori25, Waite Katie25, Miller David25, Brounce Ginger25, George-Adebayo Constance25, Adebayo Adeolu25, Wallan Jessica25, Vogel Claudia25, Munoz Sebastian25, Watson Cassandra25, Singleton David25, Rivon Maria25, Sevier Amanda25, Del Pilar Arnold25, Spangler Amber25, Rao Sohail25, Cantu Luis25, Krishna Arvind25, Evans Kathy25, Falkner Tylene25, Kerr Brandi25, Spees Robert25, Marta Mailyn25, Harrington Amanda25, Dolor Rowena25, Frazier Madison25, Vergara Lorraine25, Wilson Jessica25, Burruss Valencia25, Hurst Terri25, Ofotokun Igho25, Rebolledo Pauline25, Prabhu Rajesh25, Klicka Krystal25, Lightfeather Amber25, James Vicki25, Rogers Marcella25, Parihar Pradeep25, Torress De'Ambra25, Oragwu Chukwuemeka25, Oguego Ngozi25, Pillai Rajesh25, Juma Mustafa25, Ghaly Emad25, Al-Haddadin Dafer25, Ramirez Courtney25, Hassanien Gammal25, Ismail Samah25, Meltzer Andrew25, Moran Seamus25, Brehaut Scott25, Roche Angelina25, Mehta Manisha25, Koppinger Nicole25, Baez Jose25, Pagan Ivone25, Abdelsayed Dallal25, Aziz Mina25, Robinson Philip25, Nguyen Julie25, Pardue Victoria25, Hammons Lisa25, Ruiz-Unger Juan25, Gonzalez Susan25, Reyes Lionel25, Cienki John25, Jimenez Gisselle25, Wong Matthew25, Yuan Ying25, Li Jenny25, Szeto Jeremy25, Stelmash Lauren25, Haight Daniel25, Lamb Deryl25, Harper Amron25, Pyram-Bernard Nancy25, Quintero Arlen25, Adhami Eftim25, Maria Josette25, Paudel Diksha25, Raymond Oksana25, Summers Jeffrey25, Turner Tammy25, Lenert Leslie25, Gallegos Sam25, Szwast Elizabeth Ann25, Abdulghani Ahsan25, Vasoya Pravin25, Miller Conrad25, Wiley Hawa25, Shah Nirav25, Klein Tovah25, Castex Julie25, Feliciano Phillip25, Olivo Jacqueline25, Ghaly Marian25, Javed Zainub25, Nawrocki Alexandra25, Vecchiarelli Anthony25, Vigil Nikki25, Cherukuri Vijaya25, Burden Erica25, Linn Dawn25, Fisher Laura25, Patel Vijay25, Patel Praksha25, Patel Yuti25, Ellison Leonard25, Harrison Jeffrey25, Shah Binod25, Shah Sugata25, Singh Upinder25, Donahue Julia25, Jazayeri Yasmin25, Gupta Anita25, Chandrasekar N25, Moritz Beth25, Fortt Tabitha25, Fortt Anisa25, Jones-Ince Ingrid25, McKee Alix25, Schattinger Christy25, Wilson Jason25, Farlow Brenda25, Finlaw Lillian25, Richwine Randall25, Williams Tearani25, Paizer Penny25, Carson Lisa25, Michelson Edward25, Austin Danielle25, Khetpal Sangeeta25, Cantrell Tiffany25, Franklin Drew25, Marshall Karissa25, Mahadevan Arvind25, Rosequist Madelyn25, Gnoni Martin25, Daffner Crystal25, VandeWeerd Carla25, Roberts Mitchell25, D'Andrea Mark25, Swink Wayne25, Powers-Fletcher Margaret25, Mukunzi Sylvere25, Hensley Jamie25, Manning Brittney25, Isache Carmen25, Bowman Jennifer25, Callaghan-Brown Angelique25, Scott Taylor25, Schwasinger-Schmidt Tiffany25, Cornejo Ashlie25, Almanzar Maria25, Ginsburg Letty25, Hajaz Americo25, Bramante Carolyn25, Robinson Matthew25, Seithel Michelle25, Sekikawa Akira25, Klawson Emily25, Ostrosky Luis25, Umana Virginia25, Patterson Thomas25, Tragus Robin25, Jackson Patrick25, Hallowell Caroline25, Haughey Heather25, Vaidya-Tank Bhavna25, Gould Cameron25, Goyal Parul25, Gatewood Carly25, Williamson John25, Seagle Hannah25, Salsgiver Elizabeth25, Armas Eddie25, Cheng Jhonsai25, Huerta Priscilla25, Garcia-Diaz Julia25, Aamodt David25, Ayers JaMario25, Collins Jess25, Graves John25, Grindstaff James25, Lai Jessica25, Lopez Itzel25, Marlin Jessica25, Merkel Alyssa25, Nwosu Sam25, Obregon Savannah25, Orozco Dirk25, Perez-Torres Yoli25, Prato Nelson25, Ratcliff Colleen25, Rhode Max25, Shirey-Rice Jana25, Vermillion Krista25, Tan Hsi-Nien25, Tregoning Seibert25, Vance Meghan25, Vongsamphanh Amber25, Weir Maria25, Zaleski Nicole25, Bozzette Samuel25, Passamani Gene25,
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. Vanderbilt University Medical Center, Nashville, Tennessee 5. School of Data Science, University of Virginia, Charlottesville 6. Clinical Trials Center of Middle Tennessee, Franklin 7. University Medical Center New Orleans, Louisiana State University Health Sciences Center, New Orleans 8. Jadestone Clinical Research, LLC, Silver Spring, Maryland 9. David Kavtaradze, Inc, Cordele, Georgia 10. Lakeland Regional Medical Center, Lakeland, Florida 11. Focus Clinical Research Solutions, Charlotte, North Carolina 12. Department of Emergency Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania 13. Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida 14. Weill Cornell Medicine, New York, New York 15. Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland 16. Veterans Affairs Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Nashville 17. National Center for Advancing Translational Sciences, Bethesda, Maryland 18. Foundation for the National Institutes of Health, Bethesda, Maryland 19. Stakeholder Advisory Committee, Pittsburgh, Pennsylvania 20. Biomedical Advanced Research and Development Authority, Washington, DC 21. University of Colorado School of Medicine, Aurora 22. Division of Pulmonary, Critical Care and Sleep Medicine, University of Missouri-Kansas City School of Medicine, Kansas City 23. Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 24. Department of Health Outcomes & Biomedical Informatics, College of Medicine, University of Florida, Gainesville 25. for the Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators
Abstract
ImportanceIt is unknown whether ivermectin, with a maximum targeted dose of 600 μg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19.ObjectiveTo evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, for the treatment of early mild to moderate COVID-19.Design, Setting, and ParticipantsThe ongoing Accelerating COVID-19 Therapeutic Interventions and Vaccines 6 (ACTIV-6) platform randomized clinical trial was designed to evaluate repurposed therapies among outpatients with mild to moderate COVID-19. A total of 1206 participants older than 30 years with confirmed COVID-19 experiencing at least 2 symptoms of acute infection for less than or equal to 7 days were enrolled at 93 sites in the US from February 16, 2022, through July 22, 2022, with follow-up data through November 10, 2022.InterventionsParticipants were randomly assigned to receive ivermectin, with a maximum targeted dose of 600 μg/kg (n = 602) daily, or placebo (n = 604) for 6 days.Main Outcomes and MeasuresThe primary outcome was time to sustained recovery, defined as at least 3 consecutive days without symptoms. The 7 secondary outcomes included a composite of hospitalization, death, or urgent/emergent care utilization by day 28.ResultsAmong 1206 randomized participants who received study medication or placebo, the median (IQR) age was 48 (38-58) years, 713 (59.1%) were women, and 1008 (83.5%) reported receiving at least 2 SARS-CoV-2 vaccine doses. The median (IQR) time to sustained recovery was 11 (11-12) days in the ivermectin group and 11 (11-12) days in the placebo group. The hazard ratio (posterior probability of benefit) for improvement in time to recovery was 1.02 (95% credible interval, 0.92-1.13; P = .68). Among those receiving ivermectin, 34 (5.7%) were hospitalized, died, or had urgent or emergency care visits compared with 36 (6.0%) receiving placebo (hazard ratio, 1.0 [95% credible interval, 0.6-1.5]; P = .53). In the ivermectin group, 1 participant died and 4 were hospitalized (0.8%); 2 participants (0.3%) were hospitalized in the placebo group and there were no deaths. Adverse events were uncommon in both groups.Conclusions and RelevanceAmong outpatients with mild to moderate COVID-19, treatment with ivermectin, with a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo did not improve time to sustained 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
26 articles.
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