Clinical trial NCT04552821: Study of Biomarkers in Patients of Sepsis Complicated With Acute Respiratory Distress Syndrome (ARDS)
Official title: Study of Biomarkers in Blood and Alveolar Lavage Fluid Samples of Sepsis Patients Complicated With Acute Respiratory Distress Syndrome (ARDS)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sepsis
Acute Respiratory Distress Syndrome
Keywords: sepsis
Acute Respiratory Distress Syndrome
metabonomics
biomarkers
oxidative stress
Inflammation
Lead sponsor: Tianjin Nankai Hospital
Sponsor class: OTHER
First posted: 2020-09-17
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with sepsis complicated with ARDS

Brief summary: 1. Title: Study of Biomarkers in Blood and Alveolar Lavage Fluid Samples of Sepsis Patients Complicated With Acute Respiratory Distress Syndrome (ARDS)
2. Research center: Single-center study.
3. Design of the research: A prospective and cohort study.
4. Object of the research: Patients（age≥18 years）those who meet the diagnostic criteria of sepsis complicated with ARDS and grouped into ARDS group and non-ARDS adults receiving mechanical ventilation as control.
5. Sample size of the research: Not less than 30 patients in each group.
6. Research approach: After admission to ICU, patients who meet the criteria are divided into mild group and moderate/severe group according to the severity of ARDS. In addition, blood and alveolar lavage fluid were collected within 24 hours for metabonomics analysis, and differential metabolites were screened out to prove the differentiation ability of differential metabolites between mild and moderate/severe ARDS patients. Then, MSEA and STITCH analysis were performed, and the relationship between different metabolites, HO-1 protein, oxidative stress and inflammatory markers in serum and alveolar lavage fluid were determined. And whether differential metabolites are associated with 28-day mortality in patients with moderate/severe ARDS.
7. Aim of the research: The metabolomics techniques were used to compare the differences between sepsis patients with mild ARDS and moderate/severe ARDS. And determine the relationship between different metabolites, HO-1 protein, oxidative stress and inflammatory markers, as well as the predictive effect of metabolites on 28-day mortality in patients.
8. Statistical analysis: Analytical study.
9. The estimated duration of the study：1-2 years.

Detailed description: This study is a single-center, prospective, retrospective study. In this study, the serum samples and alveolar lavage fluid of patients with sepsis complicated with ARDS were studied by using high performance liquid chromatography (HPLC) tandem electrospray four-stage rod time-of-flight mass spectrometry (LC-ESI-Q-TOF-MS). Aim to screen out the different metabolites between patients with mild and moderate/severe sepsis complicated with ARDS. HO-1 protein, oxidative stress and inflammatory markers in serum and alveolar lavage fluid were measured simultaneously to explore the relationship between HO-1, oxidative inflammatory markers and metabolic markers. In addition, a biomarker model was established to provide an important reference for assisting ARDS disease management and predicting the adverse outcome of patients with sepsis complicated with ARDS.

Eligibility criteria: Inclusion Criteria:

* At least 18 years old
* Patients with sepsis who meet the criteria for sepsis -3
* Patients complicated with Acute Respiratory Distress Syndrome who meet the Berlin diagnostic criteria
* Agree to participate in this study and sign informed consent

Exclusion Criteria:

* Refuse to participate in this study
* Patient with HIV infection, patients in pregnancy or breast stage
* Patient had chronic respiratory ailments
* Patients are now being included in another study
* In the opinion of the attending physician or researcher, there are other conditions that are not appropriate for the study

Primary outcomes:
measure: Multivariate data analysis of the metabolites
timeFrame: an average of 1 year
measure: Multivariate data analysis of the metabolites
timeFrame: 12 months
Secondary outcomes:
measure: Screening of differentially expressed metabolites as potential mortality predictors for sepsis complicated with ARDS
timeFrame: an average of 1 year
measure: Pathway Analysis of the differential metabolites
timeFrame: 12 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin NanKai hospital
state: Tianjin
Study officials:
affiliation: Tianjin Nankai Hospital
name: Jianbo Yu, MD,PhD
role: STUDY_CHAIR
References:
citation: Xu J, Pan T, Qi X, Tan R, Wang X, Liu Z, Tao Z, Qu H, Zhang Y, Chen H, Wang Y, Zhang J, Wang J, Liu J. Increased mortality of acute respiratory distress syndrome was associated with high levels of plasma phenylalanine. Respir Res. 2020 Apr 30;21(1):99. doi: 10.1186/s12931-020-01364-6.
citation: Lin S, Yue X, Wu H, Han TL, Zhu J, Wang C, Lei M, Zhang M, Liu Q, Xu F. Explore potential plasma biomarkers of acute respiratory distress syndrome (ARDS) using GC-MS metabolomics analysis. Clin Biochem. 2019 Apr;66:49-56. doi: 10.1016/j.clinbiochem.2019.02.009. Epub 2019 Feb 16.
citation: Metwaly SM, Winston BW. Systems Biology ARDS Research with a Focus on Metabolomics. Metabolites. 2020 May 19;10(5):207. doi: 10.3390/metabo10050207.
citation: Stringer KA, Serkova NJ, Karnovsky A, Guire K, Paine R 3rd, Standiford TJ. Metabolic consequences of sepsis-induced acute lung injury revealed by plasma (1)H-nuclear magnetic resonance quantitative metabolomics and computational analysis. Am J Physiol Lung Cell Mol Physiol. 2011 Jan;300(1):L4-L11. doi: 10.1152/ajplung.00231.2010. Epub 2010 Oct 1.
citation: Evans CR, Karnovsky A, Kovach MA, Standiford TJ, Burant CF, Stringer KA. Untargeted LC-MS metabolomics of bronchoalveolar lavage fluid differentiates acute respiratory distress syndrome from health. J Proteome Res. 2014 Feb 7;13(2):640-9. doi: 10.1021/pr4007624. Epub 2013 Dec 9.