Procalcitonin testing combined with NEWS2 evaluation compared with usual care based on NEWS2 for identification of sepsis and antibiotic initiation in the emergency department in England and Wales (PRONTO): a multicentre, randomised, controlled, open-label, phase 3 trial.

In emergency department settings, accurate diagnosis can be challenging, as many non-infectious conditions have similar presenting features and there is no gold standard diagnostic test, which can lead to misdirected use of antibiotics.

在急诊科环境中，准确诊断可能具有挑战性，因为许多非感染性疾病具有类似的临床表现，且没有金标准的诊断测试，这可能导致抗生素的误用。

Procalcitonin is a well characterised biomarker that responds rapidly and with high specificity to the presence of bacterial infection.

降钙素原是一种特征明确的生物标志物，它能迅速且特异性地对细菌感染的存在作出反应。

We aimed to investigate whether supplementing current practice with rapid procalcitonin testing would improve recognition of sepsis and allow reduced antibiotic prescribing with at least no change in overall mortality.

我们旨在研究，通过补充当前实践，使用快速降钙素原检测是否能改善对败血症的认识，并允许减少抗生素处方，同时至少不改变总死亡率。

Methods

A parallel, two-arm, open-label, individually randomised controlled trialwas done in 20 hospital emergency departments within 17 National Health Service (NHS) Trusts or Health Boards across England and Wales.

在英格兰和威尔士的17个国家卫生服务（NHS）信托或卫生委员会的20个医院急诊科进行了一项平行、双臂、开放标签、个体随机对照试验。

Patients aged 16 years and older with suspected sepsis were randomly assigned to either usual care or procalcitonin-guided care in a 1:1 ratio via a centrally controlled web-based randomisation programme.

年龄在16岁及以上的疑似脓毒症患者通过一个中心控制的基于网络的随机化程序，以1:1的比例随机分配到常规护理组或降钙素原指导的护理组。

Participants, research staff, those assessing outcomes, and statisticians analysing the data were not masked to group assignment.

参与者、研究人员、结果评估人员以及分析数据的统计学家均未对分组情况实施盲法。

Participants in the usual care group were assessed according to standard clinical management based on National Early Warning Score 2 (NEWS2).

常规护理组的参与者根据基于国家早期预警评分2（NEWS2）的标准临床管理进行了评估。

In the procalcitonin-guided care group, rapid procalcitonin testing was used in combination with NEWS2 assessment by use of a guidance-only algorithm for clinicians.

在降钙素原指导的护理组中，结合使用NEWS2评估，通过仅提供指导的算法为临床医生使用快速降钙素原测试。

This algorithm for clinical management was used for both usual care and procalcitonin-guided care groups and clinicians were free to use, ignore, or deviate from the algorithm.

这种临床管理算法被用于常规护理和降钙素原指导护理组，临床医生可以自由地使用、忽略或偏离该算法。

The co-primary endpoints were intravenous antibiotic initiation at 3 h (superiority) and 28-day mortality (non-inferiority) from triage assessment, assessed in all randomly assigned consenting participants with data for both co-primary outcomes available.

主要共研究终点是在3小时内开始静脉抗生素治疗（优势性）和从分诊评估起28天内的死亡率（非劣效性），评估所有随机分配且同意参与的参与者，这些参与者对于两个主要共研究终点的数据均可用。

Non-inferiority was concluded for 28-day mortality if the upper bound of the 90% CI was below a 2·5% margin on the risk difference scale.

如果90%置信区间上限在风险差异尺度上低于2.5%的边界，则得出28天死亡率的非劣效性结论。

All patients who were randomly assigned to one of the two groups and who consented to data collection at baseline were included in adverse eventanalysis for the period they were included in the study.

所有被随机分配到两组之一并且同意在基线时进行数据收集的患者都被纳入了不良事件分析，时间为他们被纳入研究的期间。

The study was registered with ISRCTN (ISRCTN54006056) and is complete.

该研究已在ISRCTN注册（ISRCTN54006056），研究已完成。

Results

Between Nov 20, 2020, and Nov 1, 2023, a total of 7667 patients were recruited and randomly assigned to the usual care group (n=3836) or the procalcitonin-guided care group (n=3831). 5453 patients (2748 female, 2703 male, 1 non-binary, 1 data for gender missing) were included in the primary analysis population (2715 usual care, 2738 procalcitonin-guided care).

在2020年11月20日至2023年11月1日期间，共招募了7667名患者，并随机分配到常规护理组（n=3836）或降钙素原指导的护理组（n=3831）。5453名患者（2748名女性，2703名男性，1名非二元性别，1名性别数据缺失）被纳入主要分析人群（2715名常规护理，2738名降钙素原指导的护理）。

The last 28-day follow-up was on Nov 29, 2023.

最后的28天随访是在2023年11月29日完成的。

There was no difference in intravenous antibiotic initiation at 3 h from triage assessment between the two groups: 48·4% (1325/2738 participants) in the procalcitonin-guided care group versus 48·2% (1308/2715 participants) in the usual care group (adjusted risk difference -0·08 percentage points, 95% CI -2·58 to 2·42; p=0·95).

两组在从分诊评估后3小时内静脉抗生素启动方面没有差异：在降钙素原指导护理组中为48.4%（1325/2738名参与者），在常规护理组中为48.2%（1308/2715名参与者）（调整后的风险差异为-0.08个百分点，95%置信区间-2.58至2.42；p=0.95）。

Mortality at 28 days was lower in the procalcitonin-guided care group: 13·6% (372/2738 participants) in the procalcitonin-guided care group versus 16·6% (450/2715 participants) in the usual care group (adjusted risk difference -3·12 percentage points, 90% CI -4·68 to -1·57; p=0·0009).

28天的死亡率在降钙素原指导护理组中较低：在降钙素原指导护理组中为13.6%（372/2738名参与者），在常规护理组中为16.6%（450/2715名参与者）（调整后的风险差异为-3.12个百分点，90%置信区间-4.68至-1.57；p=0.0009）。

The upper bound of the 90% CI was below the non-inferiority margin of 2·5 percentage points and the point of no effect, implying both non-inferiority and superiority at the one-sided 5% level.

90%置信区间的上限低于2.5个百分点的非劣效性边界和无效应点，意味着在单侧5%水平上既具有非劣效性也具有优越性。

In the primary analysis population, the procalcitonin test result was considered in clinical decision making in 64·7% (1771/2738) of participants in the procalcitonin-guided care group.

在主要分析人群中，64.7%（1771/2738）的参与者的临床决策考虑了降钙素原测试结果，这些参与者属于降钙素原指导下的护理组。

Improved mortality was not explained by findings of planned subgroup, sensitivity, or secondary analyses.

改善的死亡率无法通过计划的亚组、敏感性或次要分析的发现来解释。

A total of 180 adverse events were recorded, 53·3% (96 events in 57 [1·9%] of 2968 participants) in the usual care group and 46·7% (84 events in 66 [2·2%] of 3042 participants) in the procalcitonin-guided care group.

共记录了180起不良事件，其中常规护理组占53.3%（2968名参与者中有57人发生了96起事件），而降钙素原指导的护理组占46.7%（3042名参与者中有66人发生了84起事件）。

One (<1%) of 2042 participants in the procalcitonin-guided care group reported a serious adverse eventprobably or definitely attributable to the procalcitonin test.

在2042名接受降钙素原指导治疗的参与者中，有1名（<1%）报告了可能或肯定与降钙素原测试相关的严重不良事件。

interpretation

Making a procalcitonin-guided algorithm available to clinicians in emergency departments did not change intravenous antibiotic initiation at 3 h in patients managed as suspected sepsis, but a decrease in 28-day mortality was seen and further research is needed to understand this finding.

向急诊科医生提供降钙素原指导算法并未改变在疑似败血症患者中3小时内静脉抗生素的启动，但观察到28天死亡率有所下降，需要进一步研究以理解这一发现。

funding

National Institute for Health and Care Research.

国家健康与护理研究所。