Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19: A Randomized Clinical Trial.

Autor:	Naggie S; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.; Department of Medicine, Duke University School of Medicine, Durham, North Carolina., Boulware DR; Division of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis., Lindsell CJ; Vanderbilt University Medical Center, Nashville, Tennessee., Stewart TG; School of Data Science, University of Virginia, Charlottesville., Slandzicki AJ; Clinical Trials Center of Middle Tennessee, Franklin., Lim SC; University Medical Center New Orleans, Louisiana State University Health Sciences Center, New Orleans., Cohen J; Jadestone Clinical Research, LLC, Silver Spring, Maryland., Kavtaradze D; David Kavtaradze, Inc, Cordele, Georgia., Amon AP; Lakeland Regional Medical Center, Lakeland, Florida., Gabriel A; Focus Clinical Research Solutions, Charlotte, North Carolina., Gentile N; Department of Emergency Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania., Felker GM; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.; Department of Medicine, Duke University School of Medicine, Durham, North Carolina., Jayaweera D; Department of Medicine, Miller School of Medicine, University of Miami, Miami, Florida., McCarthy MW; Weill Cornell Medicine, New York, New York., Sulkowski M; Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland., Rothman RL; Vanderbilt University Medical Center, Nashville, Tennessee., Wilson S; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina., DeLong A; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina., Remaly A; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina., Wilder R; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina., Collins S; Vanderbilt University Medical Center, Nashville, Tennessee.; Veterans Affairs Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center (GRECC), Nashville., Dunsmore SE; National Center for Advancing Translational Sciences, Bethesda, Maryland., Adam SJ; Foundation for the National Institutes of Health, Bethesda, Maryland., Thicklin F; Stakeholder Advisory Committee, Pittsburgh, Pennsylvania., Hanna GJ; Biomedical Advanced Research and Development Authority, Washington, DC., Ginde AA; University of Colorado School of Medicine, Aurora., Castro M; Division of Pulmonary, Critical Care and Sleep Medicine, University of Missouri-Kansas City School of Medicine, Kansas City., McTigue K; Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania., Shenkman E; Department of Health Outcomes & Biomedical Informatics, College of Medicine, University of Florida, Gainesville., Hernandez AF; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.; Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
Jazyk:	angličtina
Zdroj:	JAMA [JAMA] 2023 Mar 21; Vol. 329 (11), pp. 888-897.
DOI:	10.1001/jama.2023.1650
Abstrakt:	Importance: It 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. Objective: To 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 Participants: The 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. Interventions: Participants 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 Measures: The 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. Results: Among 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 Relevance: Among 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 Registration: ClinicalTrials.gov Identifier: NCT04885530.
Databáze:	MEDLINE
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