Prospective Observational Study of Biology of Critical Illness
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Change in severity of illness measured by SOFA score
研究概览
简要总结
Advanced stages of the response to life-threatening infection, severe trauma, or other physiological insults often lead to exhaustion of the homeostatic mechanisms that sustain normal blood pressure and oxygenation. These syndromic presentations often meet the diagnostic criteria of sepsis and/or the acute respiratory distress syndrome (ARDS), the two most common syndromes encountered in the intensive care unit (ICU). Although critical illness syndromes, such as sepsis and ARDS, have separate clinical definitions, they often overlap clinically and share several common injury mechanisms. Moreover, there are no specific therapies for critically ill patients, and as a consequence, approximately 1 in 4 patients admitted to the ICU will not survive.
The purpose of this observational study is to identify early patient biologic factors that are present at the time of ICU admission that will help diagnose critical illness syndromes earlier, identify who could benefit most from specific therapies, and enable the discovery of new treatments for syndromes such as sepsis and ARDS.
详细描述
Background:
Critical illness syndromes, such as sepsis and ARDS, are associated with tremendous heterogeneity in patient predisposing risk factors, mechanisms of acute insult contributing to infection, presenting symptoms, response to therapies, as well as short and long-term outcomes. Since the first standardization of sepsis and ARDS definitions >30 years ago, significant insight into biological mechanisms contributing to critical illness syndromes have been made. However, there are many important unanswered questions that prevent accurate diagnosis, treatment, and prognosis of patients who present to the ICU with early symptoms consistent with critical illness.
Of the many gaps about the biology of sepsis and ARDS that remain unanswered, the following are particularly important: (1) what constitutes immune system dysregulation; (2) how the immune system response depends on interaction with the infecting pathogens; (3) what biologic traits distinguish other diagnoses that mimic these syndromes; (4) what are the mechanisms of genetic polymorphisms in patient outcomes. To address these questions and to improve our understanding of these complex and heterogenous syndromes, a multifaceted and collaborative approach is needed. This study will investigate the biology of early sepsis in critically ill patients by developing a longitudinal prospective observational cohort called Early Severe illness TrAnslational BioLogy InformaticS in Humans (ESTABLISH).
Specific objectives:
Objective 1: To study biologic mechanisms of immune system regulation during early critical illness. The main questions that will be addressed include: (1) how immune function at the time of admission and over the course of the ICU stay is related to clinical complications; (2) how anatomic compartmentalization of immune responses is associated with clinical complications; (3) how immune responses in different anatomic locations contribute to endothelial cell injury; (4) how macrophages contribute to distal organ injury and long-term clinical complications.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years old
- •≤48h since ICU admission
- •ICU admission within 72h of presentation to the emergency department (ER)
- •Clinical critical illness suspected on the basis of any one of the following:
- •Altered mental status (GCS<15)
- •Cardiovascular collapse (presence of any: Heart rate >90, systolic blood pressure <90, presence of vasopressors, lactate >2.0)
- •Respiratory collapse (presence of any: respiratory rate >20, PaCO₂ <32 mm Hg, supplemental oxygen, invasive or non-invasive ventilation)
- •Suspected severe infection (presence of any: temperature >38°C or <36°C, white blood cell (WBC) count >12,000/mm³ or <4,000/mm³, presence of 1 or more antibiotics at the time of ICU admission)
排除标准
- •Age <18 years old
- •>72h since ICU admission
- •Admission to ICU in patients >72h after the presentation to the ER
- •No evidence of critical illness (ICU admission due to bed-spacing)
结局指标
主要结局
Change in severity of illness measured by SOFA score
时间窗: From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months
SOFA
Change in severity of illness measured by MODS score
时间窗: From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months
MODS
Severity of illness measured by SOFA score
时间窗: At the time of ICU admission
SOFA
Risk of developing nosocomial infections during ICU admission
时间窗: Assessed daily until discharge from ICU, through study completion, an average of 1 year
Development of any of the following: Ventilator Associated Pneumonia, Central Line Infections, Clostridium difficile-Associated Diarrhea, Blood stream infections
Severity of illness measured by MODS score
时间窗: At the time of ICU admission
MODS
Hospital disposition
时间窗: Determined at the time of discharge from the hospital, through study completion, an average of 1 year
Survival, death
Severity of illness measured by APACHE score
时间窗: At the time of ICU admission
APACHE
Change in severity of illness measured by APACHE score
时间窗: From the time of ICU admission, assessed daily until death or discharge from ICU, up to 12 months
APACHE
次要结局
- Neurocognitive dysfunction(1, 6, and 12 months after ICU discharge)
- Physiological outcomes(0, 24, 48, and 72 hours after ICU admission)
研究者
Aleks Leligdowicz
Clinician Scientist
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's