Impact of Early Sepsis Care Guided by the National Early Warning Score 2 in the Emergency Department

Early Sepsis Care With the National Early Warning Score 2-guided Sepsis Hour-1 Bundle in the Emergency Department: A Hybrid Type 1 Effectiveness-Implementation Pilot Stepped Wedge Randomised Controlled Trial (NEWS-1 Trial Pilot Study)

The goal of this pilot clinical trial is to determine the feasibility of conducting a fully powered type 1 hybrid effectiveness-implementation trial on early sepsis care that is guided by early warning score in adult emergency department (ED) patients who have infection. The main questions it aims to answer are:

• Is it feasible to execute the trial procedure and fulfill the progression criteria to a full-scale trial?
• Does the Surviving Sepsis Campaign (SSC) Hour-1 Bundle care reduce the mortality of adult ED patients with a clinical diagnosis of infection and a National Early Warning Score 2 (NEWS2) equal to or greater than 5?
• What are the barriers to and facilitators of the implementation of the SSC Hour-1 Bundle in the ED settings?

Participants will receive the following SSC Hour-1 Bundle care during the intervention period:

• Blood lactate level measurement
• Blood cultures collection before administering antibiotics
• Broad-spectrum antibiotics
• Intravenous fluid
• Vasopressors if the blood pressure remains low during or after fluid replacement to maintain the mean arterial blood pressure equal to or greater than 65 mmHg

Researchers will compare patients who receive SSC Hour-1 Bundle triggered by a NEWS2 equal to or greater than 5 and patients who receive standard treatment based on clinical judgement to see if the SSC Hour-1 that is triggered by a high NEWS2 score could reduce mortality of adult ED patients with infection.

Despite international endorsement and promulgation, the uptake of the sepsis-care bundles remains low across health-care settings. In most cases, clinicians are still offering sepsis care based on individual clinical judgement, intuition, skills, and available time and resources, leading to a variable standard of care at best and a suboptimal patient outcome in many cases. Significant knowledge gaps exist in the real-world effectiveness of sepsis bundles that are objectively triggered by the early warning score and in the best implementation strategy of sepsis bundle in the ED setting.

The sepsis care model in which the SSC Hour-1 Bundle is triggered objectively by a high NEWS2 score (≥ 5) (known as "NEWS-1 care" in this study) will be evaluated in this study. This pilot study is a type 1 hybrid effectiveness-implementation study, which contains all the major components of a planned full-scale hybrid trial intended to involve a larger sample size from more local EDs. This pilot study has two essential components:

First, the effectiveness component will evaluate the effect of the SSC Hour-1 Bundle in reducing 30-day all-cause mortality in adult patients presenting to the ED with a clinical diagnosis of infection and a NEWS2 ≥ 5. A prospective, stepped-wedge, cluster-randomized trial, which combines elements of a standard cluster-randomized design (intervention applied in clusters) and a before-after design (in which each cluster switches to the intervention), will be conducted in four EDs in Hong Kong. All study sites will start with an initial period of standard care; they will then switch in random order at intervals of two months to the NEWS-1 care in a unidirectional fashion until all hospitals have crossed over. Recruitment will continue in all study sites until the end of the trial.

Second, the implementation component will use a mixed-methods design to evaluate the uptake of the SSC Hour-1 Bundle using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework, and determine the barriers to and facilitators of its implementation in daily practice.

The primary outcome of this pilot study is the feasibility of a full-scale type 1 hybrid trial on the NEWS-1 care, which will be determined based on the 14 pre-defined progression criteria to assess the feasibility of emergency staff in multiple centres to screen, recognise and recruit patients with suspected sepsis and to execute trial procedures; the feasibility of trial methods to decide whether a fully-powered trial should be undertaken to determine the safety and effectiveness of the intervention; and the feasibility of research staff to conduct the implementation evaluation. Please refer to the published study protocol for the 14 progression criteria.

We will not proceed to a full-scale trial if there is clear evidence of significant harm (safety criterion) or effect (equipoise criterion). As for the other progression criteria, no weighing will be added during evaluation and they will be considered collectively as we conclude the study.

Inclusion Criteria:

ED patients aged ≥ 18 years who fulfil ALL of the following criteria:

• a clinical diagnosis of infection made by the treating emergency physicians
• require hospital admission
• a NEWS2 ≥ 5

Exclusion Criteria:

• age < 18 years
• currently pregnant
• neutropenic or post-chemotherapy fever, for which ED protocols for early antibiotics apply
• an advanced directive with a ceiling-of-care
• refusal of consent/pre-existing mental illness rendering consent impossible
• refusal of hospitalization