[저자] Wesley H Self, Matthew W Semler, Lindsay M Leither, Jonathan D Casey, Derek C Angus, Roy G Brower, Steven Y Chang, Sean P Collins, John C Eppensteiner, Michael R Filbin, D Clark Files, Kevin W Gibbs, Adit A Ginde, Michelle N Gong, Frank E Harrell Jr, Douglas L Hayden, Catherine L Hough, Nicholas J Johnson, Akram Khan, Christopher J Lindsell, Michael A Matthay, Marc Moss, Pauline K Park, Todd W Rice, Bryce R H Robinson, David A Schoenfeld, Nathan I Shapiro, Jay S Steingrub, Christine A Ulysse, Alexandra Weissman, Donald M Yealy, B Taylor Thompson, Samuel M Brown, National Heart, Lung, and Blood Institute PETAL Clinical Trials Network, Jay Steingrub, Howard Smithline, Bogdan Tiru, Mark Tidswell, Lori Kozikowski, Sherell Thornton-Thompson, Leslie De Souza, Peter Hou, Rebecca Baron, Anthony Massaro, Imoigele Aisiku, Lauren Fredenburgh, Raghu Seethala, Lily Johnsky, Richard Riker, David Seder, Teresa May, Michael Baumann, Ashley Eldridge, Christine Lord, Nathan Shapiro, Daniel Talmor, Thomas O’Mara, Charlotte Kirk, Kelly Harrison, Lisa Kurt, Margaret Schermerhorn, Valerie Banner-Goodspeed, Katherine Boyle, Nicole Dubosh, Michael Filbin, Kathryn Hibbert, Blair Parry, Kendall Lavin-Parsons, Natalie Pulido, Brendan Lilley, Carl Lodenstein, Justin Margolin, Kelsey Brait, Alan Jones, James Galbraith, Rebekah Peacock, Utsav Nandi, Taylor Wachs, Michael Matthay, Kathleen Liu, Kirsten Kangelaris, Ralph Wang, Carolyn Calfee, Kimberly Yee, Gregory Hendey, Steven Chang, George Lim, Nida Qadir, Andrea Tam, Rebecca Beutler, Joseph Levitt, Jenny Wilson, Angela Rogers, Rosemary Vojnik, Jonasel Roque, Timothy Albertson, James Chenoweth, Jason Adams, Skyler Pearson, Maya Juarez, Eyad Almasri, Mohamed Fayed, Alyssa Hughes, Shelly Hillard, Ryan Huebinger, Henry Wang, Elizabeth Vidales, Bela Patel, Adit Ginde, Marc Moss, Amiran Baduashvili, Jeffrey McKeehan, Lani Finck, Carrie Higgins, Michelle Howell, Ivor Douglas, Jason Haukoos, Terra Hiller, Carolynn Lyle, Alicia Cupelo, Emily Caruso, Claudia Camacho, Stephanie Gravitz, James Finigan, Christine Griesmer, Pauline Park, Robert Hyzy, Kristine Nelson, Kelli McDonough, Norman Olbrich, Mark Williams, Raj Kapoor, Jean Nash, Meghan Willig, Henry Ford, Jayna Gardner-Gray, Mayur Ramesh, Montefiore Moses, Michelle Ng Gong, Michael Aboodi, Ayesha Asghar, Omowunmi Amosu, Madeline Torres, Savneet Kaur, Jen-Ting Chen, Aluko Hope, Brenda Lopez, Kathleen Rosales, Jee Young You, Jarrod Mosier, Cameron Hypes, Bhupinder Natt, Bryan Borg, Elizabeth Salvagio Campbell, R Duncan Hite, Kristin Hudock, Autumn Cresie, Faysal Alhasan, Jose Gomez-Arroyo, Abhijit Duggal, Omar Mehkri, Andrei Hastings, Debasis Sahoo, Francois Abi Fadel, Susan Gole, Valerie Shaner, Allison Wimer, Yvonne Meli, Alexander King, Thomas Terndrup, Matthew Exline, Sonal Pannu, Emily Robart, Sarah Karow, Catherine Hough, Bryce Robinson, Nicholas Johnson, Daniel Henning, Monica Campo, Stephanie Gundel, Sakshi Seghal, Sarah Katsandres, Sarah Dean, Akram Khan, Olivia Krol, Milad Jouzestani, Peter Huynh, Alexandra Weissman, Donald Yealy, Denise Scholl, Peter Adams, Bryan McVerry, David Huang, Derek Angus, Jordan Schooler, Steven Moore, Clark Files, Chadwick Miller, Kevin Gibbs, Mary LaRose, Lori Flores, Lauren Koehler, Caryn Morse, John Sanders, Caitlyn Langford, Kristen Nanney, Masiku MdalaGausi, Phyllis Yeboah, Peter Morris, Jamie Sturgill, Sherif Seif, Evan Cassity, Sanjay Dhar, Marjolein de Wit, Jessica Mason, Andrew Goodwin, Greg Hall, Abbey Grady, Amy Chamberlain, Samuel Brown, Joseph Bledsoe, Lindsay Leither, Ithan Peltan, Nathan Starr, Melissa Fergus, Valerie Aston, Quinn Montgomery, Rilee Smith, Mardee Merrill, Katie Brown, Brent Armbruster, Estelle Harris, Elizabeth Middleton, Robert Paine, Stacy Johnson, Macy Barrios, John Eppensteiner, Alexander Limkakeng, Lauren McGowan, Tedra Porter, Andrew Bouffler, J. Clancy Leahy, Bennet deBoisblanc, Matthew Lammi, Kyle Happel, Paula Lauto, Wesley Self, Jonathan Casey, Matthew Semler, Sean Collins, Frank Harrell, Christopher Lindsell, Todd Rice, William Stubblefield, Christopher Gray, Jakea Johnson, Megan Roth, Margaret Hays, Donna Torr, Arwa Zakaria, David Schoenfeld, Taylor Thompson, Douglas Hayden, Nancy Ringwood, Cathryn Oldmixon, Christine Ulysse, Richard Morse, Ariela Muzikansky, Laura Fitzgerald, Samuel Whitaker, Adrian Lagakos, Roy Brower, Lora Reineck, Neil Aggarwal, Karen Bienstock, Michelle Freemer, Myron Maclawiw, Gail Weinmann, Laurie Morrison, Mark Gillespie, Richard Kryscio, Daniel Brodie, Wojciech Zareba, Anne Rompalo, Michael Boeckh, Polly Parsons, Jason Christie, Jesse Hall, Nicholas Horton, Laurie Zoloth, Neal Dickert, Deborah Diercks
[Category] 임상, 진단, 치료제,
[Article Type] Randomized Controlled Trial
Abstract
Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed.
Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19.
Design, setting, and participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.
Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237).
Main outcomes and measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality.
Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]).
Conclusions and relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults.
Trial registration: ClinicalTrials.gov: NCT04332991 .
All Keywords
【초록키워드】 COVID-19, Treatment, coronavirus disease, Efficacy, coronavirus, Hospitalized, Trial, Hydroxychloroquine, randomization, intensive care, hospital, Infection, 28-day mortality, Noninvasive ventilation, Respiratory illness, nasal, outcome, clinical status, Randomized, Adults, extracorporeal membrane oxygenation, clinical, Patient, death, Placebo, multicenter, patients, Invasive mechanical ventilation, 7-category ordinal scale, Support, supplemental oxygen, interquartile range, acute respiratory syndrome, adjusted odds ratio, Sample size, Primary outcome, hydroxychloroquine group, Secondary outcomes, placebo group, median age, activities, secondary outcome, placebo-controlled randomized trial, interim analysis, respiratory symptom, absolute difference, doses, positive, Randomly, multivariable, IMPROVE, greater, enrolled, analyzed, died, blinded, significantly, conducted, receiving, median, determine, assigned, groups, discharged, adults hospitalized, duration of symptom, the placebo group, use of hydroxychloroquine, with COVID-19, 【제목키워드】 clinical, status, Effect, Day,
{{{ 추상적인 }}}
{{ 중요성: }} 2019년 코로나바이러스 질병(COVID-19) 치료를 위한 하이드록시클로로퀸의 효능에 대한 데이터가 필요합니다.
{{ 목적: }} 하이드록시클로로퀸이 COVID-19로 입원한 성인에게 효과적인 치료법인지 확인합니다.
{{ 디자인, 설정 및 참가자: }} 이것은 미국의 34개 병원에서 수행된 다기관, 맹검, 위약 대조 무작위 시험이었습니다. 중증급성호흡기증후군 코로나바이러스 2 감염으로 인한 호흡기 증상으로 입원한 성인은 2020년 4월 2일에서 6월 19일 사이에 등록되었으며 최종 결과 평가는 2020년 7월 17일이었습니다. 계획된 표본 크기는 510명의 환자였으며 중간 분석은 102명마다 계획되었습니다. 환자가 등록되었습니다. 이 시험은 479명의 환자 표본으로 이루어진 무익에 대한 네 번째 중간 분석에서 중단되었습니다.
{{ 중재: }} 환자를 무작위로 하이드록시클로로퀸(2회 용량에 대해 400mg 1일 2회, 8회 용량에 대해 200mg 1일 2회)(n = 242) 또는 위약(n = 237)에 할당했습니다.
{{ 주요 결과 및 측정: }} 1차 결과는 1(사망)에서 7(퇴원 및 정상적인 활동 수행 가능)까지의 7개 범주 서수 척도로 평가된 무작위 배정 후 14일의 임상 상태였습니다. 1차 결과는 다변수 비례 승산 모델로 분석되었으며, 조정 승산비(aOR)가 1.0보다 크면 위약보다 하이드록시클로로퀸에서 더 유리한 결과를 나타냅니다. 이 시험에는 28일 사망률을 포함하여 12개의 2차 결과가 포함되었습니다.
{{ 결과: }} 무작위 배정된 환자 479명 중(연령 중앙값, 57세, 여성 44.3%, 히스패닉/라틴계 37.2%, 흑인 23.4%, 중환자실에서 20.1%, 양압 없이 산소 보충을 받고 있는 46.8%, 11.5%는 비침습적 인공호흡 또는 비강 고유량 산소를 투여받았고 6.7%는 침습적 기계 환기 또는 체외막 산소화를 투여받았으며 433명(90.4%)은 14일에 1차 결과 평가를 완료했으며 나머지는 임상 상태를 귀속했습니다. 무작위 배정 전 증상의 중앙값 지속 기간은 5일(사분위수 범위[IQR], 3-7일)이었습니다. 14일의 순서 결과 척도에 대한 임상 상태는 하이드록시클로로퀸과 위약 그룹 간에 유의한 차이가 없었습니다(중앙값 [IQR] 점수, 6[4-7] 대 6[4-7]; aOR, 1.02[95% CI, 0.73]). 1.42]). 12개의 2차 결과 중 어느 것도 그룹 간에 유의한 차이가 없었습니다. 무작위 배정 후 28일에 하이드록시클로로퀸 그룹의 환자 241명 중 25명(10.4%)과 위약 그룹의 환자 236명 중 25명(10.6%)이 사망했습니다(절대 차이, -0.2%[95% CI, -5.7%~5.3%] ], aOR, 1.07[95% 신뢰구간, 0.54~2.09]).
{{ 결론 및 관련성: }} COVID-19로 인한 호흡기 질환으로 입원한 성인 중 히드록시클로로퀸을 사용한 치료는 위약과 비교하여 14일째에 임상 상태를 유의하게 개선하지 않았습니다. 이러한 결과는 COVID-19 치료를 위한 히드록시클로로퀸의 사용을 뒷받침하지 않습니다 -19 입원 성인 중.
{{ 시험 등록: }} ClinicalTrials.gov: NCT04332991 .