福斯他替尼用于治疗住院的新冠肺炎低氧血症成人患者：一项随机临床试验。
Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial.
作者信息
Collins Sean P, Shotwell Matthew S, Strich Jeffrey R, Gibbs Kevin W, de Wit Marjolein, Files D Clark, Harkins Michelle, Hudock Kris, Merck Lisa H, Moskowitz Ari, Apodaca Krystle D, Barksdale Aaron, Safdar Basmah, Javaheri Ali, Sturek Jeffrey M, Schrager Harry, Iovine Nicole M, Tiffany Brian, Douglas Ivor, Levitt Joseph, Ginde Adit A, Hager David N, Shapiro Nathan, Duggal Abhijit, Khan Akram, Lanspa Michael, Chen Peter, Gentile Nina, Harris Estelle, Gong Michelle, Sellers Subhashini, Goodwin Andrew J, Tidswell Mark A, Filbin Michael, Desai Neeraj, Gutiérrez Felix, Estrada Vicente, Burgos Joaquin, Boyles Tom, Paño-Pardo Jose R, Hussen Nazreen, Rosenberg Yves, Troendle James, Bernard Gordon R, Bistran-Hall Amanda J, Walsh Kelly, Casey Jonathan D, DeClercq Josh, Joly Meghan Morrison, Pulley Jill, Rice Todd W, Schildcrout Jonathan S, Wang Li, Semler Matthew W, Self Wesley H
机构信息
Department of Emergency Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Veterans Affairs Tennessee Valley Healthcare System, Geriatric Research, Education and Clinical Center, Nashville, Tennessee.
出版信息
JAMA Netw Open. 2024 Dec 2;7(12):e2448215. doi: 10.1001/jamanetworkopen.2024.48215.
IMPORTANCE
Fostamatinib, a spleen tyrosine kinase inhibitor, has been reported to improve outcomes of COVID-19.
OBJECTIVE
To evaluate the efficacy and safety of fostamatinib in adults hospitalized with COVID-19 and hypoxemia.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3, placebo-controlled, double-blinded randomized clinical trial was conducted at 41 US sites and 21 international sites between November 17, 2021, and September 27, 2023; the last follow-up visit was December 31, 2023. Participants were adults aged 18 years or older hospitalized with acute SARS-CoV-2 infection and hypoxemia. Data were analyzed between January 10 and March 8, 2024.
INTERVENTIONS
Fostamatinib, 150 mg orally twice daily for 14 days, or placebo.
MAIN OUTCOMES AND MEASURES
The primary outcome was oxygen-free days, an ordinal outcome classifying a participant's status at day 28 based on mortality and duration of supplemental oxygen use. An adjusted odds ratio (AOR) greater than 1.0 was considered to indicate superiority of fostamatinib over placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included elevated transaminase values, neutropenia, and hypertension.
RESULTS
Of the 400 participants randomized (median age, 67 years [IQR, 58-76 years]; 210 [52.5%] men), 199 received fostamatinib and 201 received placebo. The mean (SD) number of oxygen-free days was 13.4 (12.4) in the fostamatinib group and 14.2 (12.1) in the placebo group (unadjusted mean difference, -1.26 days [95% CI, -3.52 to 1.00 days]; AOR, 0.82 [95% credible interval (CrI), 0.58-1.17]). Mortality at 28 days occurred in 22 of 195 patients (11.3%) in the fostamatinib group and 16 of 197 (8.1%) in the placebo group (AOR, 1.44; 95% CrI, 0.72-2.90). Aspartate aminotransferase elevation occurred more commonly in the fostamatinib group (23 [11.6%]) than in the placebo group (11 [5.5%]; AOR, 2.28; 95% CrI, 1.07-4.84). Other safety outcomes were similar between groups.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial of adults hospitalized with COVID-19 and hypoxemia, fostamatinib did not increase the number of oxygen-free days compared with placebo. These results do not support the hypothesis that fostamatinib improves outcomes among adults hospitalized with hypoxemia during the Omicron era.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04924660.
重要性
福斯替尼是一种脾酪氨酸激酶抑制剂，据报道可改善新冠病毒疾病（COVID-19）的预后。
目的
评估福斯替尼对因COVID-19和低氧血症住院的成年人的疗效和安全性。
设计、地点和参与者：这项多中心、3期、安慰剂对照、双盲随机临床试验于2021年11月17日至2023年9月27日在美国的41个地点和21个国际地点进行；最后一次随访时间为2023年12月31日。参与者为18岁及以上因急性严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染和低氧血症住院的成年人。数据于2024年1月10日至3月8日进行分析。
干预措施
福斯替尼，口服150毫克，每日两次，共14天，或安慰剂。
主要结局和测量指标
主要结局为无吸氧天数，这是一个序贯结局，根据死亡率和补充氧气使用时间对参与者在第28天的状态进行分类。调整后的优势比（AOR）大于1.0被认为表明福斯替尼优于安慰剂。一个关键的次要结局是28天全因死亡率。安全性结局包括转氨酶值升高、中性粒细胞减少和高血压。
结果
在400名随机分组的参与者中（中位年龄67岁[四分位间距，58 - 76岁]；210名[52.5%]为男性），199名接受福斯替尼治疗，201名接受安慰剂治疗。福斯替尼组无吸氧天数的均值（标准差）为13.4（12.4）天，安慰剂组为14.2（12.1）天（未调整的均值差异为 -1.26天[95%置信区间，-3.52至1.00天]；AOR为0.82[95%可信区间（CrI），0.58 - 1.17]）。福斯替尼组195名患者中有22名（11.3%）在28天内死亡，安慰剂组197名中有16名（8.1%）死亡（AOR为1.44；95% CrI，0.72 - 2.90）。福斯替尼组天冬氨酸转氨酶升高的情况比安慰剂组更常见（23例[11.6%]对比11例[5.5%]；AOR为2.28；95% CrI，1.07 - 4.84）。其他安全性结局在两组之间相似。
结论及相关性
在这项针对因COVID-19和低氧血症住院的成年人的随机临床试验中，与安慰剂相比，福斯替尼并未增加无吸氧天数。这些结果不支持福斯替尼可改善奥密克戎时代因低氧血症住院的成年人预后这一假设。
试验注册
ClinicalTrials.gov标识符：NCT04924660
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