Clinical trial NCT05731349: Impact of Early Sepsis Care Guided by the National Early Warning Score 2 in the Emergency Department
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Septic Shock
Keywords: Sepsis
National Early Warning Score
Surviving Sepsis Campaign Hour-1 Bundle
Emergency Department
Implementation Sciences
Lead sponsor: The University of Hong Kong
Sponsor class: OTHER
Collaborators: name: Queen Mary Hospital, Hong Kong
name: Pamela Youde Nethersole Eastern Hospital
name: Prince of Wales Hospital, Shatin, Hong Kong
name: Tuen Mun Hospital
First posted: 2023-02-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Stepped-wedge, cluster-randomized trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause 30-day mortality (in full-scale stepped wedge RCT)
timeFrame: 30 days
Secondary outcomes:
Other outcomes:
measure: All-cause in-hospital mortality (in full-scale stepped wedge RCT)
timeFrame: From the date of recruitment until the date of death from any cause or date of hospital discharge, whichever comes first, assessed up to 90 days
measure: All-cause 90-day mortality (in full-scale stepped wedge RCT)
timeFrame: 90 days
measure: Sepsis-related in-hospital mortality (in full-scale stepped wedge RCT)
timeFrame: From the date of recruitment until the date of death from sepsis or date of hospital discharge, whichever comes first, assessed up to 90 days
measure: Intensive care unit admission (in full-scale stepped wedge RCT)
timeFrame: From the date of recruitment until the date of first documented intensive care unit admission or date of hospital discharge or date of death, whichever comes first, assessed up to 90 days
measure: Ventilator-free days over 30 days (in full-scale stepped wedge RCT)
timeFrame: Over 30 days following recruitment
measure: The need for renal replacement therapy (in full-scale stepped wedge RCT)
timeFrame: From the date of recruitment until the date of first documented renal replacement therapy or date of hospital discharge or date of death, whichever comes first, assessed up to 90 days
measure: The total length of stay in the emergency department (in full-scale stepped wedge RCT)
timeFrame: From the time of emergency department registration to the time of check out from the emergency department or time of death in the emergency department, whichever comes first, assessed up to 7 days
measure: The total length of stay in the intensive care unit (in full-scale stepped wedge RCT)
timeFrame: From the date of intensive care unit admission until the date of discharge from the intensive care unit or date of death, whichever comes first, assessed up to 90 days
measure: The total length of stay in the general ward (in full-scale stepped wedge RCT)
timeFrame: From the date of hospital admission to general ward until the date of hospital discharge or date of transfer out of general ward or date of death, whichever comes first, assessed up to 90 days
measure: The time to surgery (in full-scale stepped wedge RCT)
timeFrame: From the of emergency department registration until the first documented time of surgery or time of hospital discharge or time of death, whichever comes first, assessed up to 90 days
Locations:
city: Hong Kong
country: Hong Kong
facility: Accident and Emergency Department, Pamela Youde Nethersole Eastern Hospital
city: Hong Kong
country: Hong Kong
facility: Accident and Emergency Department, Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Accident and Emergency Department, Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Accident and Emergency Department, Tuen Mun Hospital
Study officials:
affiliation: The University of Hong Kong
name: Pui Kin Lam, MBBS, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lam RPK, Hung KKC, Lui CT, Kwok WS, Lam WWT, Lau EHY, Sridhar S, Ng PYT, Cheng CH, Tsang TC, Tsui MSH, Graham CA, Rainer TH. Early sepsis care with the National Early Warning Score 2-guided Sepsis Hour-1 Bundle in the emergency department: hybrid type 1 effectiveness-implementation pilot stepped wedge randomised controlled trial (NEWS-1 TRIPS) protocol. BMJ Open. 2024 Feb 1;14(2):e080676. doi: 10.1136/bmjopen-2023-080676.