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

被引:5
|
作者
Potter, Gail E. [1 ]
Bonnett, Tyler [2 ]
Rubenstein, Kevin [2 ]
Lindholm, David A. [3 ,4 ]
Rapaka, Rekha R. [5 ]
Doernberg, Sarah B. [6 ]
Lye, David C. [7 ,8 ]
Mularski, Richard A. [9 ,10 ]
Hynes, Noreen A. [11 ]
Kline, Susan [12 ]
Paules, Catharine, I [13 ]
Wolfe, Cameron R. [14 ]
Frank, Maria G. [15 ,16 ]
Rouphael, Nadine G. [17 ]
Deye, Gregory A. [18 ]
Sweeney, Daniel A. [19 ]
Colombo, Rhonda E. [20 ,21 ,22 ]
Davey, Richard T. [23 ]
Mehta, Aneesh K. [24 ,25 ]
Whitaker, Jennifer A. [26 ,27 ]
Castro, Jose G. [28 ]
Amin, Alpesh N. [29 ]
Colombo, Christopher J. [3 ,20 ]
Levine, Corri B. [30 ]
Jain, Mamta K. [31 ,32 ]
Maves, Ryan C. [21 ,33 ]
Marconi, Vincent C. [34 ,35 ]
Grossberg, Robert [36 ]
Hozayen, Sameh [37 ]
Burgess, Timothy H. [38 ]
Atmar, Robert L. [39 ]
Ganesan, Anuradha [40 ,41 ]
Gomez, Carlos A. [42 ]
Benson, Constance A. [43 ]
de Castilla, Diego Lopez [44 ]
Ahuja, Neera [45 ]
George, Sarah L. [46 ,47 ]
Nayak, Seema U. [18 ]
Cohen, Stuart H. [48 ]
Lalani, Tahaniyat [38 ,49 ]
Short, William R. [50 ]
Erdmann, Nathaniel [51 ]
Tomashek, Kay M. [18 ]
Tebas, Pablo [52 ]
机构
[1] NIAID, Biostat Res Branch, NIH, Rockville, MD USA
[2] Frederick Natl Lab Canc Res, Clin Monitoring Res Program Directorate, Frederick, MD USA
[3] Uniformed Serv Univ Hlth Sci, Dept Med, Room A3060, Bethesda, MD 20814 USA
[4] Brooke Army Med Ctr, Joint Base San Antonio F, TX USA
[5] Univ Maryland, Ctr Vaccine Dev & Global Hlth, Sch Med, Baltimore, MD USA
[6] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA
[7] Tan Tock Seng Hosp, Natl Ctr Infect Dis, Yong Loo Lin Sch Med, Singapore, Singapore
[8] Lee Kong Chian Sch Med, Singapore, Singapore
[9] Northwest Permanente PC, Dept Pulm & Crit Care Med, Portland, OR USA
[10] Kaiser Permanente Northwest Ctr Hlth Res, Portland, OR USA
[11] Johns Hopkins Univ, Dept Med, Div Infect Dis, Sch Med, Baltimore, MD USA
[12] Univ Minnesota Med Sch, Dept Med, Div Infect Dis & Int Med, Minneapolis, MN USA
[13] Penn State Hlth Milton S Hershey Med Ctr, Div Infect Dis, Hershey, PA USA
[14] Duke Univ Med Ctr, Dept Med, Div Infect Dis, Durham, NC USA
[15] Denver Hlth Hosp Author, Dept Med, Aurora, CO USA
[16] Univ Colorado, Sch Med, Aurora, CO USA
[17] Hope Clin, Infect Dis Div, Emory Vaccine Ctr, Atlanta, GA USA
[18] NIAID, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[19] Univ Calif San Diego, Dept Med, Div Pulm Crit Care & Sleep Med, San Diego, CA 92103 USA
[20] Madigan Army Med Ctr, Tacoma, WA 98431 USA
[21] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Bethesda, MD 20814 USA
[22] Henry M Jackson Fdn Adv Mil Med Inc, Bethesda, MD USA
[23] NIAID, NIH, Bethesda, MD USA
[24] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA
[25] Natl Emerging Special Pathogens Training & Educ C, Atlanta, GA USA
[26] Baylor Coll Med, Dept Mol Virol & Microbiol, Sect Infect Dis, Houston, TX USA
[27] Baylor Coll Med, Sect Infect Dis, Dept Med, Houston, TX 77030 USA
[28] Univ Miami, Div Infect Dis, Miami, FL USA
[29] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA
[30] Univ Texas Med Branch, Dept Internal Med, Div Infect Dis, Galveston, TX 77555 USA
[31] UT Southwestern Med Ctr, Dept Internal Med, Div Infect Dis & Geog Med, Dallas, TX USA
[32] Parkland Hlth & Hosp Syst, Dallas, TX USA
[33] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA
[34] Emory Univ, Rollins Sch Publ Hlth, Sch Med, Atlanta, GA USA
[35] Atlanta Vet Affairs Med Ctr, Atlanta, GA USA
[36] Albert Einstein Coll Med, Dept Med, Div Infect Dis, Montefiore Med Ctr, Bronx, NY USA
[37] Univ Minnesota, Div Hosp Med, Dept Med, Minneapolis, MN USA
[38] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biostat, Infect Dis Clin Res Program, Bethesda, MD USA
[39] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
[40] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Henry M Jackson Fdn Adv Mil Med Inc, Dept Prevent Med & Biostat, Bethesda, MD USA
[41] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA
[42] Univ Nebraska Med Ctr, Div Infect Dis, Dept Internal Med, Omaha, NE USA
[43] Univ Calif San Diego, Div Infect Dis & Global Publ Hlth, San Diego, CA USA
[44] Evergreen Hlth Med Ctr, Div Infect Dis, Kirkland, WA USA
[45] Stanford Univ, Dept Internal Med, Med Ctr, Palo Alto, CA USA
[46] St Louis Univ, St Louis, MO USA
[47] St Louis VA Med Ctr, St Louis, MO USA
[48] Univ Calif Davis, Div Infect Dis, Sacramento, CA USA
[49] Naval Med Ctr Portsmouth, Portsmouth, Hants, England
[50] Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA
关键词
PROPENSITY SCORE; GUIDELINES; FAILURE; CARE;
D O I
10.7326/M22-2116
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1716 / +
页数:13
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