For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
57
views
16
references
 Top references
cited by
21
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
2 collections
    0
    shares
      221
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

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

      Author(s): 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 1 , 2 , 13 , 14 , 15 , 4 , 1 , 1 , 1 , 1 , 4 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 1 , 2 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , 25 , Accelerating Covid-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group and Investigators
      Publication date (Electronic):
      Journal: JAMA
      Publisher: American Medical Association (AMA)

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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

          Related collections

          Most cited references16

          • Record: found
          • Abstract: found
          • Article: not found

          The FDA-approved Drug Ivermectin inhibits the replication of SARS-CoV-2 in vitro

          Leon Caly, Julian Druce, Mike Catton … (2020)
          Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 able to effect ∼5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
          Article 0 comments Cited 955 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

            Angélica Jayk Bernal, Monica M. Gomes da Silva, Dany Musungaie … (2021)
            Abstract Background New treatments are needed to reduce the risk of progression of coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that is active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods We conducted a phase 3, double-blind, randomized, placebo-controlled trial to evaluate the efficacy and safety of treatment with molnupiravir started within 5 days after the onset of signs or symptoms in nonhospitalized, unvaccinated adults with mild-to-moderate, laboratory-confirmed Covid-19 and at least one risk factor for severe Covid-19 illness. Participants in the trial were randomly assigned to receive 800 mg of molnupiravir or placebo twice daily for 5 days. The primary efficacy end point was the incidence hospitalization or death at day 29; the incidence of adverse events was the primary safety end point. A planned interim analysis was performed when 50% of 1550 participants (target enrollment) had been followed through day 29. Results A total of 1433 participants underwent randomization; 716 were assigned to receive molnupiravir and 717 to receive placebo. With the exception of an imbalance in sex, baseline characteristics were similar in the two groups. The superiority of molnupiravir was demonstrated at the interim analysis; the risk of hospitalization for any cause or death through day 29 was lower with molnupiravir (28 of 385 participants [7.3%]) than with placebo (53 of 377 [14.1%]) (difference, −6.8 percentage points; 95% confidence interval, −11.3 to −2.4; P=0.001). In the analysis of all participants who had undergone randomization, the percentage of participants who were hospitalized or died through day 29 was lower in the molnupiravir group than in the placebo group (6.8% [48 of 709] vs. 9.7% [68 of 699]; difference, −3.0 percentage points; 95% confidence interval, −5.9 to −0.1). Results of subgroup analyses were largely consistent with these overall results; in some subgroups, such as patients with evidence of previous SARS-CoV-2 infection, those with low baseline viral load, and those with diabetes, the point estimate for the difference favored placebo. One death was reported in the molnupiravir group and 9 were reported in the placebo group through day 29. Adverse events were reported in 216 of 710 participants (30.4%) in the molnupiravir group and 231 of 701 (33.0%) in the placebo group. Conclusions Early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19. (Funded by Merck Sharp and Dohme; MOVe-OUT ClinicalTrials.gov number, NCT04575597.)
            Article 0 comments Cited 786 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial

              Eric J. Lenze, Caline Mattar, Charles F. Zorumski … (2020)
              Coronavirus disease 2019 (COVID-19) may lead to serious illness as a result of an excessive immune response. Fluvoxamine may prevent clinical deterioration by stimulating the σ-1 receptor, which regulates cytokine production.
              Article 0 comments Cited 268 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: JAMA
                Abbreviated Title: JAMA
                Publisher: American Medical Association (AMA)
                ISSN (Print): 0098-7484
                Publication date (Electronic): February 20 2023
                Affiliations
                [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
                Article
                DOI: 10.1001/jama.2023.1650
                PubMed ID: 36807465
                SO-VID: 831cb7ca-1e71-42dc-8934-fb21630fcc5c
                Copyright © © 2023
                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content221

                See all similar

                Cited by21

                See all cited by

                Most referenced authors719

                See all reference authors