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Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.
Potter, Gail E; Bonnett, Tyler; Rubenstein, Kevin; Lindholm, David A; Rapaka, Rekha R; Doernberg, Sarah B; Lye, David C; Mularski, Richard A; Hynes, Noreen A; Kline, Susan; Paules, Catharine I; Wolfe, Cameron R; Frank, Maria G; Rouphael, Nadine G; Deye, Gregory A; Sweeney, Daniel A; Colombo, Rhonda E; Davey, Richard T; Mehta, Aneesh K; Whitaker, Jennifer A; Castro, Jose G; Amin, Alpesh N; Colombo, Christopher J; Levine, Corri B; Jain, Mamta K; Maves, Ryan C; Marconi, Vincent C; Grossberg, Robert; Hozayen, Sameh; Burgess, Timothy H; Atmar, Robert L; Ganesan, Anuradha; Gomez, Carlos A; Benson, Constance A; Lopez de Castilla, Diego; Ahuja, Neera; George, Sarah L; Nayak, Seema U; Cohen, Stuart H; Lalani, Tahaniyat; Short, William R; Erdmann, Nathaniel; Tomashek, Kay M; Tebas, Pablo.
  • Potter GE; Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland (G.E.P.).
  • Bonnett T; Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland (T.B., K.R.).
  • Rubenstein K; Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research, Frederick, Maryland (T.B., K.R.).
  • Lindholm DA; Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and Brooke Army Medical Center, Joint Base San Antonio-Fort Sam Houston, Texas (D.A.L.).
  • Rapaka RR; University of Maryland Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland (R.R.R.).
  • Doernberg SB; Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, San Francisco, California (S.B.D.).
  • Lye DC; National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, and Lee Kong Chian School of Medicine, Singapore (D.C.L.).
  • Mularski RA; Department of Pulmonary and Critical Care Medicine, Northwest Permanente PC, and Kaiser Permanente Northwest Center for Health Research, Portland, Oregon (R.A.M.).
  • Hynes NA; Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland (N.A.H.).
  • Kline S; Department of Medicine, Division of Infectious Diseases and International Medicine, University of Minnesota Medical School, Minneapolis, Minnesota (S.K.).
  • Paules CI; Division of Infectious Diseases, Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania (C.I.P.).
  • Wolfe CR; Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham, North Carolina (C.R.W.).
  • Frank MG; Department of Medicine, Denver Health Hospital Authority, Denver, Colorado, and University of Colorado School of Medicine, Aurora, Colorado (M.G.F.).
  • Rouphael NG; Hope Clinic, Emory Vaccine Center, Infectious Diseases Division, Atlanta, Georgia (N.G.R.).
  • Deye GA; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (G.A.D., S.U.N., K.M.T.).
  • Sweeney DA; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, San Diego, California (D.A.S.).
  • Colombo RE; Madigan Army Medical Center, Tacoma, Washington, Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland (R.E.C.).
  • Davey RT; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (R.T.D.).
  • Mehta AK; Division of Infectious Diseases, Emory University School of Medicine, and National Emerging Special Pathogens Training and Education Center, Atlanta, Georgia (A.K.M.).
  • Whitaker JA; Departments of Molecular Virology and Microbiology and Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas (J.A.W.).
  • Castro JG; Division of Infectious Diseases, University of Miami, Miami, Florida (J.G.C.).
  • Amin AN; Department of Medicine, University of California, Irvine, Irvine, California (A.N.A.).
  • Colombo CJ; Madigan Army Medical Center, Tacoma, Washington, and Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland (C.J.C.).
  • Levine CB; Department of Internal Medicine, Division of Infectious Disease, University of Texas Medical Branch, Galveston, Texas (C.B.L.).
  • Jain MK; Department of Internal Medicine, Division of Infectious Disease and Geographic Medicine, UT Southwestern Medical Center, and Parkland Health & Hospital System, Dallas, Texas (M.K.J.).
  • Maves RC; Wake Forest University School of Medicine, Winston-Salem, North Carolina, and Infectious Diseases Clinical Research Program, Uniformed Services University of the Health Sciences, Bethesda, Maryland (R.C.M.).
  • Marconi VC; Emory University School of Medicine, Rollins School of Public Health, and Atlanta Veterans Affairs Medical Center, Atlanta, Georgia (V.C.M.).
  • Grossberg R; Department of Medicine, Division of Infectious Diseases, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York (R.G.).
  • Hozayen S; Department of Medicine, Division of Hospital Medicine, University of Minnesota, Minneapolis, Minnesota (S.H.).
  • Burgess TH; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland (T.H.B.).
  • Atmar RL; Department of Medicine, Baylor College of Medicine, Houston, Texas (R.L.A.).
  • Ganesan A; Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and Walter Reed National Military Medical Center, Bethesda, Marylan
  • Gomez CA; Department of Internal Medicine, Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska (C.A.G.).
  • Benson CA; Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, California (C.A.B.).
  • Lopez de Castilla D; Division of Infectious Diseases, Evergreen Health Medical Center, Kirkland, Washington (D.L.).
  • Ahuja N; Department of Internal Medicine, Stanford University Medical Center, Palo Alto, California (N.A.).
  • George SL; Saint Louis University and St. Louis VA Medical Center, Saint Louis, Missouri (S.L.G.).
  • Nayak SU; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (G.A.D., S.U.N., K.M.T.).
  • Cohen SH; Division of Infectious Diseases, University of California, Davis, Sacramento, California (S.H.C.).
  • Lalani T; Naval Medical Center Portsmouth, Portsmouth, Virginia, Infectious Disease Clinical Research Program, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and The Henry M. Jackson Foundation for the Advancement of Military Medi
  • Short WR; Department of Medicine, Division of Infectious Diseases, University of Pennsylvania, Philadelphia, Pennsylvania (W.R.S.).
  • Erdmann N; Division of Infectious Diseases, Department of Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama (N.E.).
  • Tomashek KM; Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland (G.A.D., S.U.N., K.M.T.).
  • Tebas P; Division of Infectious Diseases/Clinical Trials Unit, University of Pennsylvania, Philadelphia, Pennsylvania (P.T.).
Ann Intern Med ; 2022 Nov 29.
Article in English | MEDLINE | ID: covidwho-2145013
ABSTRACT

BACKGROUND:

The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear.

OBJECTIVE:

To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial).

DESIGN:

ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]).

SETTING:

94 hospitals in 10 countries (86% U.S. participants).

PARTICIPANTS:

Adults hospitalized with COVID-19. INTERVENTION SOC. MEASUREMENTS 28-day mortality and recovery.

RESULTS:

Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages.

LIMITATION:

Unmeasured confounding.

CONCLUSION:

Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE National Institute of Allergy and Infectious Diseases.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Language: English Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Topics: Variants Language: English Year: 2022 Document Type: Article