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Cited by 243COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchLong-Term Effects of COVID-19

The DOI matches its Crossref record; 49 of the 50 references it cites were found in a registry or an index.

Randomized trial of metformin, ivermectin, and fluvoxamine for Covid-19.

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Bramante, Carolyn T., Huling, Jared D., Tignanelli, Christopher J., Buse, John B., Liebovitz, David M., Nicklas, Jacinda M., Cohen, Kenneth, Puskarich, Michael A., Belani, Hrishikesh K., Proper, Jennifer L., Siegel, Lianne K., Klatt, Nichole R., Odde, David J., Luke, Darlette G., Anderson, Blake, Karger, Amy B., Ingraham, Nicholas E., Hartman, Katrina M., Rao, Via, Hagen, Aubrey A., Patel, Barkha, Fenno, Sarah L., Avula, Nandini, Reddy, Neha V., Erickson, Spencer M., Lindberg, Sarah, Fricton, Regina, Lee, Samuel, Zaman, Adnin, Saveraid, Hanna G., Tordsen, Walker J., Pullen, Matthew F., Biros, Michelle, Sherwood, Nancy E., Thompson, Jennifer L., Boulware, David R., Murray, Thomas A.·2022·New England Journal of Medicine
DOI 10.1056/nejmoa2201662PMC PMC9945922
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Abstract

BACKGROUND: Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications. RESULTS: A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS: None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).

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Authors
Bramante, C. T., Huling, J. D., Tignanelli, C. J., Buse, J. B., Liebovitz, D. M., Nicklas, J. M., Cohen, K., Puskarich, M. A., Belani, H. K., Proper, J. L., Siegel, L. K., Klatt, N. R., Odde, D. J., Luke, D. G., Anderson, B., Karger, A. B., Ingraham, N. E., Hartman, K. M., Rao, V., Hagen, A. A., Patel, B., Fenno, S. L., Avula, N., Reddy, N. V., Erickson, S. M., Lindberg, S., Fricton, R., Lee, S., Zaman, A., Saveraid, H. G., Tordsen, W. J., Pullen, M. F., Biros, M., Sherwood, N. E., Thompson, J. L., Boulware, D. R., & Murray, T. A.
Affiliations
  • University of Minnesota (US)
  • University of North Carolina at Chapel Hill (US)
  • Northwestern University (US)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2022-08-18
Volume
387
Issue
7
Pages
599-610
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2201662
PMC
PMC9945922
OpenAlex
W4292148078
Cited by
242
References
50
Citations by year
2026: 19 · 2025: 31 · 2024: 63 · 2023: 94 · 2022: 35
FWCI
27.26
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • UnitedHealth Group Foundation
  • Fast Grants
  • National Center for Advancing Translational Sciences (KL2TR002492, UL1TR002494)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK124654-01A1)
  • Rainwater Charitable Foundation
  • The Parsemus Foundation
Topics
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Clinical Neurology › Long-Term Effects of COVID-19
Keywords
COVID-19 pandemic, SARS-CoV-2, metformin, ivermectin, fluvoxamine, drug repurposing, antiviral therapy, disease progression prevention, hypoxemia, hospitalization, mortality, obesity, overweight, emergency department visits, COVID-19 vaccination
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, COVID-19 Drug Treatment, Adult, Aged, Aged, 80 and over, Hypoxia, Double-Blind Method, Female, Humans, Ivermectin, Male, Metformin, Middle Aged, Obesity, Pregnancy, Pregnancy Complications, Infectious, Fluvoxamine, Overweight

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