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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Diagnostic test: gut and nasal microbiota detection

Detailed Description

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:

1. 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.
2. 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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Zhanguo Liu, M.D.PhD; Phone Number: +86-2062782927; Email: zhguoliu@163.com
• Study Contact Backup: Name: Xilan Tan, M.D.PhD; Phone Number: +86-13751824998; Email: 147270875@qq.com

Study Locations

• China
  • Guangdong
    • Dongguan, Guangdong, China
      • Recruiting
      • Department of Critical Care Medicine of Dongguan People's Hospital, Dongguan
      • Contact: Yuping Liao, MD; Phone Number: +86-13650171253; Email: yupliao@163.com
    • Guanzhou, Guangdong, China
      • Recruiting
      • Department of Critical Care Medicine of Zhujiang Hospital
      • Contact: zhanguo Liu, M.D.PhD; Phone Number: +862062782927; Email: zhguoliu@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

In this study, patients who met the Sepsis 3.0 diagnostic criteria and with PCT ≥ 2ng/ml and will be recruited.

Description

Inclusion Criteria:

1. Meet the 2016 International Sepsis Guidelines diagnostic criteria (sepsis 3.0).
2. Serum procalcitonin≥ 2 ng/mL at enrollment.

Exclusion Criteria:

Patients will be excluded if participants meet any of the following criteria:

1. age<18 years old or > 80 years
2. pregnancy or lactation
3. solid organ or bone marrow transplant
4. advanced pulmonary fibrosis
5. HIV-positive
6. neutropenia;
7. hematological/lymphatic tumors have no remission;
8. limited care (lack of commitment to full and aggressive support);
9. long-term use of immunosuppressive drugs or immunodeficiency;
10. advanced tumors;
11. combined with noninfectious factors leading to death (uncontrolled large bleeding, cerebral hernia, etc.);
12. Combined with autoimmune diseases
13. Paraquat poisoning
14. Combined with Nasopharyngeal carcinoma
15. Combined with chronic nasosinusitis
16. Combined with severe nasal injuries

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Modeling cohort; 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; 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.
validation cohort; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhujiang Hospital
• Investigators: Principal Investigator: Zhanguo Liu, M.D.PhD, Department of Critical Care Medicine of Zhujiang Hospital

Publications and helpful links

General Publications

• Tan XL, Liu HY, Long J, Jiang Z, Luo Y, Zhao X, Cai S, Zhong X, Cen Z, Su J, Zhou H. Septic patients in the intensive care unit present different nasal microbiotas. Future Microbiol. 2019 Mar;14(5):383-395. doi: 10.2217/fmb-2018-0349. Epub 2019 Feb 26.

Helpful Links

• The related background of this study

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: October 16, 2021
• First Submitted That Met QC Criteria: November 21, 2021
• First Posted (Actual): December 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Septic Shock; Sepsis; gut microbiota; nasal microbiota
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Sepsis; Shock, Septic
• Other Study ID Numbers: 2021-KY-108-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The datasets generated and analyzed during the study are available from the corresponding author on reasonable request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No