Dark Paul, Hossain Anower, McAuley Daniel F, Brealey David, Carlson Gordon, Clayton Jonathan C, Felton Timothy W, Ghuman Belinder K, Gordon Anthony C, Hellyer Thomas P, Lone Nazir I, Manazar Uzma, Richards Gillian, McCullagh Iain J, McMullan Ronan, McNamee James J, McNeil Hannah C, Mouncey Paul R, Naisbitt Micheal J, Parker Robert J, Poole Ruth L, Rostron Anthony J, Singer Mervyn, Stevenson Matt D, Walsh Tim S, Welters Ingeborg D, Whitehouse Tony, Whiteley Simon, Wilson Peter, Young Keith K, Perkins Gavin D, Lall Ranjit
Division of Immunology, Immunity to Infection and Respiratory Medicine, University of Manchester, Critical Care Unit, Northern Care Alliance NHS Foundation Trust, Salford Care Organization, Greater Manchester, United Kingdom.
Warwick Medical School, Clinical Trials Unit, University of Warwick, Coventry, United Kingdom.
JAMA. 2025 Feb 25;333(8):682-693. doi: 10.1001/jama.2024.26458.
For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.
To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.
DESIGN, SETTING, AND PARTICIPANTS: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.
From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care.
The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected.
Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, -2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, -0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, -2.07 to 5.45; P = .03).
Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive.
isrctn.org Identifier: ISRCTN47473244.
对于疑似脓毒症的住院重症成年患者，降钙素原（PCT）和C反应蛋白（CRP）监测方案可指导抗生素治疗的持续时间，但这些方案的效果和安全性证据仍不确定。
确定基于CRP或PCT评估做出的决策是否能安全地缩短抗生素治疗的持续时间。
设计、设置和参与者：一项多中心、干预隐藏的随机临床试验，涉及41个英国国民健康服务（NHS）重症监护病房的2760名成年人（≥18岁），这些患者在开始静脉使用抗生素治疗疑似脓毒症后24小时内需要重症监护，且可能持续使用抗生素至少72小时。
从2018年1月1日至2024年6月5日，918名患者被分配至每日PCT指导方案组，924名患者被分配至每日CRP指导方案组，918名患者被分配至标准治疗组。
主要结局为至28天的抗生素总持续时间（有效性）和全因死亡率（安全性）。次要结局包括重症监护病房数据和住院时间数据。还收集了90天全因死亡率。
在随机分组的患者中（平均年龄60.2[标准差，15.4]岁；60.3%为男性），与标准治疗相比，每日PCT指导方案组从随机分组至28天的抗生素使用持续时间显著缩短（标准治疗组平均持续时间为10.7[标准差，7.6]天，PCT组为9.8[标准差，7.2]天；平均差值为0.88天；95%置信区间为0.19至1.58，P = 0.01）。对于至28天的全因死亡率，每日PCT指导方案组不劣于标准治疗组，非劣效界值设定为5.4%（接受标准治疗的患者中有19.4%[878例中的170例]；PCT组为20.9%[879例中的184例]；绝对差值为1.57；95%置信区间为 -2.18至5.32；P = 0.02）。标准治疗与每日CRP指导方案组的抗生素使用持续时间无差异（CRP组平均持续时间为10.6[7.7]天；平均差值为0.09；95%置信区间为 -0.60至0.79；P = 0.79）。对于全因死亡率，每日CRP指导方案组与标准治疗组相比尚无定论（CRP组为21.1%[874例中的184例]；绝对差值为1.69；95%置信区间为 -2.07至5.45；P = 0.03）。
与标准治疗相比，基于PCT测量的治疗可安全地缩短抗生素使用持续时间，但CRP则不然。CRP的全因死亡率尚无定论。
isrctn.org标识符：ISRCTN47473244。
