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

Study Overview
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Brief Summary
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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
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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 trial intended to involve a larger sample size from more local EDs. This pilot study has three 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. Third, the investigators will evaluate the acceptability, feasibility and practicability of a full-scale effectiveness-implementation trial based on the 14 progression criteria.

Official Title
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Impact of 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 Study (NEWS-1 Trial Pilot Study)

Conditions
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Sepsis, Septic Shock

Intervention / Treatment
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* Other: 2018 Surviving Sepsis Campaign Hour-1 Bundle


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Stepped-wedge, cluster-randomized trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEWS-1 care<br>During the interventional period, the 2018 Sepsis Hour-1 Bundle will be initiated in the ED if NEWS2 score ≥ 5. | Other: 2018 Surviving Sepsis Campaign Hour-1 Bundle<br>* Measure lactate Obtain blood cultures before administering antibiotics Administer broad-spectrum antibiotics based on local guidelines Begin fluid resuscitation with up to 30 mL/kg crystalloid for hypotension or lactate level ≥ 4 mmol/L. Apply vasopressors if hypotensive during or after fluid resuscitation to maintain the MAP ≥ 65 mm Hg<br>|
| No Intervention: Standard care<br>During the standard care period, emergency physicians will assess the patients based on history, physical examination, laboratory tests, chest radiography or other imaging studies, and will offer treatment based on clinical expertise, intuition, and local or international guidelines | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause 30-day mortality | The number of patients who die over 30 days | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause in-hospital mortality | The number of patients who die during the index hospitalization | 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 | 
| All-cause 90-day mortality | The number of patients who die over 90 days | 90 days | 
| Sepsis-related in-hospital mortality | The number of patients who die during the index hospitalization because of sepsis, as judged by an independent emergency physician and an infectious disease specialist based on review of clinical notes and autopsy findings, if available | 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 | 
| Intensive care unit admission | Number of participants who require intensive care unit admission during the index hospitalization | 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 | 
| Ventilator-free days over 30 days | The number of ventilator-free days over 30 days after recruitment | Over 30 days following recruitment | 
| The need for renal replacement therapy | The number of patients who require renal replacement therapy during the index hospitalization that is not due to pre-existing renal failure | 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 | 
| The total length of stay in the emergency department | The total number of hour of patient stay in the emergency department | 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 | 
| The total length of stay in the intensive care unit | The total number of days of patient stay in the intensive care unit | 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 | 
| The total length of stay in the general ward | The total number of days of patient stay in the general ward | 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 | 
| The time to surgery | The number of hours from ED registration to the first surgery for cases who receive surgery during the index hospitalization | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, National Early Warning Score, Surviving Sepsis Campaign Hour-1 Bundle, Emergency Department, Implementation Sciences