Nasal and Gut Microbiota Combined Clinical Events Predicts the Prognosis of Septic Patients

Study Overview
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Brief Summary
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In this prospective, multicentered , diagnostic trial, nasal and fecal specimens will collected from patients with sepsis in two critical care units(ICU) at the enrollment day ,the third, seventh, and fourteen days after enrollment or until ICU discharge (whatever come first). Total DNA from the nasal and fecal specimens will be extracted, amplified, and sequenced to determined the characteristics of gut microbiota and nasal microbiota. Finally, the characteristics of gut microbiota and nasal microbiota combined clinical information will be used to construct a prediction model to predict the prognosis of sepsis.

Detailed Description
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Background: Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with high morbidity and mortality, and its total mortality is 10% to 52%. In sepsis, it is not clear sufficiently about the relationship between intestinal and nasal microbiota character and the development of the sepsis.The study aim to construct a prediction model to predict the prognosis and development of sepsis. Purpose: To construct a prediction model using nasal and gut microbiota combined with clinical events to predict the prognosis of patients with sepsis and development of sepsis. Analyze the characteristics of nasal and gut microbiota in patients with sepsis using microbiology. Methods: nasal and fecal specimens will collected from patients with sepsis in two critical care units(ICU) at the enrollment day ,the third, seventh, and fourteen days after enrollment or until ICU discharge (whatever come first). Total DNA from the nasal and fecal specimens will be extracted, amplified, and sequenced to determined the characteristics of gut microbiota and nasal microbiota. Meanwhile, some related clinical information also will be collected,including demographic characteristics, comorbidities, infection site, results of the microbiology experiments, vital signs, invasive tubing indwelling at enrollment，combined medication，the requirement of organ function support, laboratory indexing, sequential organ failure assessment score and Acute Physiology and Chronic Health Evaluation score. Finally, the characteristics of gut microbiota and nasal microbiota combined the clinical information will be used to construct a prediction model to predict the prognosis of sepsis. The primary outcome is the 28-day all-cause mortality. The secondary outcomes are the incidence of septic shock, the incidence of persistent inflammation- immunosuppression catabolism syndrome and the 90-day all-cause mortality.

Official Title
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Nasal and Gut Microbiota Combined Clinical Events Predicts the Prognosis of Patients With Sepsis: a Prospective, Multicentered, Diagnostic Trial

Conditions
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Sepsis, Septic Shock

Intervention / Treatment
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* Diagnostic Test: gut and nasal microbiota detection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the 2016 International Sepsis Guidelines diagnostic criteria (sepsis 3.0). Serum procalcitonin≥ 2 ng/mL at enrollment. Exclusion Criteria: Patients will be excluded if participants meet any of the following criteria: age<18 years old or > 80 years pregnancy or lactation solid organ or bone marrow transplant advanced pulmonary fibrosis HIV-positive neutropenia; hematological/lymphatic tumors have no remission; limited care (lack of commitment to full and aggressive support); long-term use of immunosuppressive drugs or immunodeficiency; advanced tumors; combined with noninfectious factors leading to death (uncontrolled large bleeding, cerebral hernia, etc.); Combined with autoimmune diseases Paraquat poisoning Combined with Nasopharyngeal carcinoma Combined with chronic nasosinusitis Combined with severe nasal injuries

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Modeling cohort<br>The population enrolled at the intensive care unit of Zhujiang Hospital of Southern Medical University in Guangdong Province, China will be used as a modeling cohort.For the patients in this cohort, the nasal and fecal specimens and related clinical information will collected to construct the prediction model. | Diagnostic Test: gut and nasal microbiota detection<br>* The nasal and fecal specimens will be collected by swabs from subjects with sepsis. After that, total DNA of nasal and gut microbiota will be extracted , amplified, and sequenced to determine the gut and nasal microbiota.<br>|
| validation cohort<br>The population enrolled at the intensive care unit of Dongguan People's Hospital in Guangdong Province, China will be used as a validation cohort. | Diagnostic Test: gut and nasal microbiota detection<br>* The nasal and fecal specimens will be collected by swabs from subjects with sepsis. After that, total DNA of nasal and gut microbiota will be extracted , amplified, and sequenced to determine the gut and nasal microbiota.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause death at 28 days | All-cause mortality from the enrollment to the 28th day | The outcome will be assessed on the 28th day from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of septic shock | Incidence of septic shock during the ICU stay. | The outcome will be assessed diurnally until ICU discharge，the longest evaluation duration is no more than 28 days | 
| Incidence of persistent inflammation-immunosuppression catabolism syndrome (PICS) | The incidence of PICS during the ICU stay. Patients who meet all the following diagnostic criteria will be diagnosed PICS: 1) the duration of ICU stay more than 14 days, 2) the level of serum C reactive protein > 50ug/dL, 3) Lymphocyte counts<0.80*10^9/L,4) serum albumin<3g/dL, 5) serum prealbumin<10mg/dL, 6) The creatinine height index<80%. 7)weight loss more than 18% or BMI<18 | The outcome will be assessed diurnally until ICU discharge，the longest evaluation duration is no more than 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sepsis, Septic Shock, nasal microbiota, gut microbiota