Study of Biomarkers in Patients of Sepsis Complicated With Acute Respiratory Distress Syndrome (ARDS)

Study of Biomarkers in Blood and Alveolar Lavage Fluid Samples of Sepsis Patients Complicated With Acute Respiratory Distress Syndrome (ARDS)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Sepsis; Acute Respiratory Distress Syndrome

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.

• Study Type: Observational
• Enrollment (Anticipated): 90

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Nankai Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients with sepsis complicated with ARDS

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Control; Non-sepsis and non-ARDS adults receiving mechanical ventilation
Sepsis complicated with mild ARDS; Patients who meet the criteria of sepsis-3, and also meet the criteria of Berlin diagnostic for mild ARDS
Sepsis complicated with moderate/severe ARDS; Patients who meet the criteria of sepsis-3, and also meet the criteria of Berlin diagnostic for moderate/severe ARDS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multivariate data analysis of the metabolites	Record the different metabolites between the control group and ARDS patients	an average of 1 year
Multivariate data analysis of the metabolites	Record the different metabolites between the patient with mild ARDS and with moderate/severe ARDS	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Screening of differentially expressed metabolites as potential mortality predictors for sepsis complicated with ARDS	Investigated the metabolites to distinguish the non-survivors from the survivors of sepsis complicated with ARDS	an average of 1 year
Pathway Analysis of the differential metabolites	Screened the differential metabolism pathway between mild ARDS and with moderate/severe ARDS, and screened the differential metabolism pathway between non-survivors and survivors	12 months

Collaborators and Investigators

• Sponsor: Tianjin Nankai Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• Metwaly SM, Winston BW. Systems Biology ARDS Research with a Focus on Metabolomics. Metabolites. 2020 May 19;10(5):207. doi: 10.3390/metabo10050207.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2020
• Primary Completion (Anticipated): June 2, 2024
• Study Completion (Anticipated): July 30, 2024

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: September 11, 2020
• First Posted (Actual): September 17, 2020

Study Record Updates

• Last Update Posted (Actual): August 4, 2022
• Last Update Submitted That Met QC Criteria: August 3, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Inflammation; biomarkers; sepsis; Acute Respiratory Distress Syndrome; oxidative stress; metabonomics
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Sepsis; Toxemia; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: NKYY_YXKT_IRB_2020_053_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All of the individual participant data collected during the trial,after deidentification will be shared.And anyone who wishes to acess the date will be available for any purpose.

Drug and device information, study documents

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