Remdesivir, Survival, and Length of Hospital Stay in US Veterans With COVID-19 | Critical Care Medicine | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Association of Remdesivir Treatment With Survival and Length of Hospital Stay Among US Veterans Hospitalized With COVID-19

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  Is remdesivir treatment associated with improved survival or shortened hospitalizations among people with COVID-19 in routine care settings?

Findings  In this cohort study of 2344 US veterans hospitalized with COVID-19, remdesivir therapy was not associated with improved 30-day survival but was associated with a significant increase in median time to hospital discharge.

Meaning  The findings suggest that routine use of remdesivir may be associated with increased use of hospital beds but not with improvements in survival.

Abstract

Importance  Randomized clinical trials have yielded conflicting results about the effects of remdesivir therapy on survival and length of hospital stay among people with COVID-19.

Objective  To examine associations between remdesivir treatment and survival and length of hospital stay among people hospitalized with COVID-19 in routine care settings.

Design, Setting, and Participants  This retrospective cohort study used data from the Veterans Health Administration (VHA) to identify adult patients in 123 VHA hospitals who had a first hospitalization with laboratory-confirmed COVID-19 from May 1 to October 8, 2020. Propensity score matching of patients initiating remdesivir treatment to control patients who had not initiated remdesivir treatment by the same hospital day was used to create the analytic cohort.

Exposures  Remdesivir treatment.

Main Outcomes and Measures  Time to death within 30 days of remdesivir treatment initiation (or corresponding hospital day for matched control individuals) and time to hospital discharge with time to death as a competing event. Associations between remdesivir treatment and these outcomes were assessed using Cox proportional hazards regression in the matched cohort.

Results  The initial cohort included 5898 patients admitted to 123 hospitals, 2374 (40.3%) of whom received remdesivir treatment (2238 men [94.3%]; mean [SD] age, 67.8 [12.8] years) and 3524 (59.7%) of whom never received remdesivir treatment (3302 men [93.7%]; mean [SD] age, 67.0 [14.4] years). After propensity score matching, the analysis included 1172 remdesivir recipients and 1172 controls, for a final matched cohort of 2344 individuals. Remdesivir recipients and matched controls were similar with regard to age (mean [SD], 66.6 [14.2] years vs 67.5 [14.1] years), sex (1101 men [93.9%] vs 1101 men [93.9%]), dexamethasone use (559 [47.7%] vs 559 [47.7%]), admission to the intensive care unit (242 [20.7%] vs 234 [19.1%]), and mechanical ventilation use (69 [5.9%] vs 45 [3.8%]). Standardized differences were less than 10% for all measures. Remdesivir treatment was not associated with 30-day mortality (143 remdesivir recipients [12.2%] vs 124 controls [10.6%]; log rank P = .26; adjusted hazard ratio [HR], 1.06; 95% CI, 0.83-1.36). Results were similar for people receiving vs not receiving dexamethasone at remdesivir initiation (dexamethasone recipients: adjusted HR, 0.93; 95% CI, 0.64-1.35; nonrecipients: adjusted HR, 1.19; 95% CI, 0.84-1.69). Remdesivir recipients had a longer median time to hospital discharge compared with matched controls (6 days [interquartile range, 4-12 days] vs 3 days [interquartile range, 1-7 days]; P < .001).

Conclusions and Relevance  In this cohort study of US veterans hospitalized with COVID-19, remdesivir treatment was not associated with improved survival but was associated with longer hospital stays. Routine use of remdesivir may be associated with increased use of hospital beds while not being associated with improvements in survival.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Accepted for Publication: April 22, 2021.

Published: July 15, 2021. doi:10.1001/jamanetworkopen.2021.14741

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Ohl ME et al. JAMA Network Open.

Corresponding Author: Michael E. Ohl, MD, MSPH, Department of Internal Medicine, Carver College of Medicine, University of Iowa, 200 Hawkins Drive, SW34 GH, Iowa City, IA 52242 (michael-ohl@uiowa.edu).

Author Contributions: Drs Ohl and Vaughan Sarrazin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Ohl, Miller, Lund, Kobayashi, Crothers.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Ohl, Kobayashi, Richardson Miell, Alexander, Vaughan Sarrazin.

Critical revision of the manuscript for important intellectual content: Ohl, Miller, Lund, Kobayashi, Richardson Miell, Beck, Crothers, Vaughan Sarrazin.

Statistical analysis: Miller, Kobayashi, Vaughan Sarrazin.

Obtained funding: Ohl, Miller.

Administrative, technical, or material support: Miller, Lund, Richardson Miell.

Supervision: Lund, Richardson Miell, Vaughan Sarrazin.

Conflict of Interest Disclosures: Dr Ohl reported receiving grants from Veterans Affairs Health Services Research and Development during the conduct of the study and consulting for Gilead Pharmaceuticals outside the submitted work. Dr Lund reported receiving grants from the US Department of Veterans Affairs during the conduct of the study. Mr Beck reported receiving grants from the Veterans Health Administration during the conduct of the study. Dr Alexander reported receiving grants from the US Department of Veterans Affairs during the conduct of the study and serving as a contract data manager for the Iowa City Veterans Affairs Medical Center Research Department outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by award C19-20-404 from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service (Dr Ohl).

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The views expressed herein are those of the authors and do not necessarily reflect the views of the US Department of Veterans Affairs.

Additional Contributions: Michihiko Goto, MD, MS, and Cassie Goedken, MPH, Center for Access & Delivery Research and Evaluation, Iowa City Veterans Affairs, provided assistance with the production of tables and figures and did not receive compensation.

References
1.
Agostini  ML , Andres  EL , Sims  AC ,  et al.  Coronavirus susceptibility to the antiviral remdesivir (GS-5734) is mediated by the viral polymerase and the proofreading exoribonuclease.   mBio. 2018;9(2):e00221-18. doi:10.1128/mBio.00221-18 PubMedGoogle Scholar
2.
Dolin  R , Hirsch  MS .  Remdesivir—an important first step.   N Engl J Med. 2020;383(19):1886-1887. doi:10.1056/NEJMe2018715 PubMedGoogle ScholarCrossref
3.
Harrington  DP , Baden  LR , Hogan  JW .  A large, simple trial leading to complex questions.   N Engl J Med. 2021;384(6):576-577. doi:10.1056/NEJMe2034294PubMedGoogle Scholar
4.
Beigel  JH , Tomashek  KM , Dodd  LE ,  et al; ACTT-1 Study Group Members.  Remdesivir for the treatment of Covid-19—final report.   N Engl J Med. 2020;383(19):1813-1826. doi:10.1056/NEJMoa2007764 PubMedGoogle ScholarCrossref
5.
Pan  H , Peto  R , Henao-Restrepo AM,  et al; WHO Solidarity Trial Consortium.  Repurposed antiviral drugs for Covid-19—interim WHO Solidarity Trial results.   N Engl J Med. 2021;384(6):497-511. doi:10.1056/NEJMoa2023184PubMedGoogle Scholar
6.
Spinner  CD , Gottlieb  RL , Criner  GJ ,  et al; GS-US-540-5774 Investigators.  Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19: a randomized clinical trial.   JAMA. 2020;324(11):1048-1057. doi:10.1001/jama.2020.16349 PubMedGoogle ScholarCrossref
7.
Wang  Y , Zhang  D , Du  G ,  et al.  Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial.   Lancet. 2020;395(10236):1569-1578. doi:10.1016/S0140-6736(20)31022-9 PubMedGoogle ScholarCrossref
8.
United States Food and Drug Administration. Remdesivir emergency use authorization letter. Accessed May 30, 2020. https://www.fda.gov/media/137564/download
9.
Rubin  D , Chan-Tack  K , Farley  J , Sherwat  A .  FDA approval of remdesivir—a step in the right direction.   N Engl J Med. 2020;383(27):2598-2600. doi:10.1056/NEJMp2032369 PubMedGoogle ScholarCrossref
10.
Infectious Diseases Society of America. ISDA guidelines on the treatment and management of patients with COVID-19. Updated December 2, 2020. Accessed December 3, 2020. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-8
11.
National Institutes of Health. Coronavirus disease 2019 (COVID-19) treatment guidelines. Accessed December 3, 2020. https://www.covid19treatmentguidelines.nih.gov/
12.
World Health Organization. Therapeutics and COVID-19: living guideline. Updated November 20, 2020. Accessed December 3, 2020. https://www.who.int/publications/i/item/therapeutics-and-covid-19-living-guideline
13.
US Department of Veterans Affairs. Veterans Health Administration. Accessed December 6, 2020. https://www.va.gov/health/
14.
VA Pharmacy Benefits Management Services. Remdesivir emergency use authorization (EUA) requirements May 2020. Accessed June 18, 2020. https://www.va.gov/covidtraining/docs/20200618_Dynamic_Drugs_in_the_Battle_of_COVID_19/Remdesivir_Emergency_Use_Authorization_Requirements.pdf
15.
von Elm  E , Altman  DG , Egger  M , Pocock  SJ , Gøtzsche  PC , Vandenbroucke  JP ; STROBE Initiative.  The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.   Lancet. 2007;370(9596):1453-1457. doi:10.1016/S0140-6736(07)61602-X PubMedGoogle ScholarCrossref
16.
VA Informatics and Computing Infrastructure. VA COVID-19 shared data resource: update. US Department of Veterans Affairs. Accessed May 29, 2021. https://www.hsrd.research.va.gov/for_researchers/cyber_seminars/archives/3834-notes.pdf
17.
Quan  H , Sundararajan  V , Halfon  P ,  et al.  Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data.   Med Care. 2005;43(11):1130-1139. doi:10.1097/01.mlr.0000182534.19832.83 PubMedGoogle ScholarCrossref
18.
Hernán  MA , Brumback  B , Robins  JM .  Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men.   Epidemiology. 2000;11(5):561-570. doi:10.1097/00001648-200009000-00012 PubMedGoogle ScholarCrossref
19.
Robins  JM , Hernán  MA , Brumback  B .  Marginal structural models and causal inference in epidemiology.   Epidemiology. 2000;11(5):550-560. doi:10.1097/00001648-200009000-00011 PubMedGoogle ScholarCrossref
20.
Horby  P , Lim  WS , Emberson  JR , et al; RECOVERY Collaborative Group.  Dexamethasone in hospitalized patients with COVID-19—preliminary report.   N Engl J Med. 2021;384(8):693-704. doi:10.1056/NEJMoa2021436PubMedGoogle Scholar
21.
Austin  PC .  Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.   Stat Med. 2009;28(25):3083-3107. doi:10.1002/sim.3697 PubMedGoogle ScholarCrossref
22.
Austin  PC , Fine  JP .  Practical recommendations for reporting Fine-Gray model analyses for competing risk data.   Stat Med. 2017;36(27):4391-4400. doi:10.1002/sim.7501 PubMedGoogle ScholarCrossref
23.
Anderson  MR , Bach  PB , Baldwin  MR . Hospital length of stay for patients with severe COVID-19: implications for remdesivir’s value. Pharmacoecon Open. 2021;5(1):129-131. doi:10.1007/s41669-020-00243-6
24.
Griffin  D , Racaniello  V . COVID-19 clinical update #41 with Dr Daniel Griffin. This Week in Virology. December 18, 2020. Accessed December 26, 2020. https://www.microbe.tv/twiv/twiv-695/
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
jn-learning_Modal_Multimedia_LoginSubscribe_Purchase
Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close

Name Your Search

Save Search
Close
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
jn-learning_Modal_SaveSearch_NoAccess_Purchase
Close

Lookup An Activity

or

Close

My Saved Searches

You currently have no searches saved.

Close
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right
Close