A Study of Exosome Proteomics and Hemodynamics in Sepsis

NCT03267160 | Completed

• 1 other identifier: 05-XD15-039
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This research will be the first study for exosomes purified in blood and urine from septic patients who had multiple organ failures. Proteomics studies in exosomes from blood or urine specimens. Analyze autophage, and apoptosis related biomarkers of exosomes by bioinformatics. To find the correlations between exosomes biomarkers and hemodynamic parameters.

Conditions

Hemodynamic Instability; Autophagy

Outcome Measures

Primary Outcomes (6)

• Change of hemodynamic parameters (heart contractility: CFI)

  Change from Baseline Cardiac function index (CFI; L/min) at 6 hours. Cardiac function index (CFI; L/min) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany)

  Baseline, 6 hours

• Change of hemodynamic parameters (preload: GEDI)

  Change from Baseline Global end-diastolic index (GEDI; mL/m2) at 6 hours. Global end-diastolic index (GEDI; mL/m2) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany).

  Baseline, 6 hours

• Change of hemodynamic parameters (afterload: SVRI)

  Change from Baseline Systemic vascular resistance index (SVRI; dynes x sec x cm-5/m2) at 6 hours. Systemic vascular resistance index (SVRI; dynes x sec x cm-5/m2) will be calculated by thermodilution method. PiCCO2 device (Pulsion Medical Systems, Munich, Germany).

  Baseline, 6 hours

• Change of hemodynamic parameters (fluid responsiveness: SVV)

  Change from Baseline Stroke volume variation (SVV, %) at 6 hours. Stroke volume variation (SVV, %) will be calculated spontaneously by PiCCO2 device (Pulsion Medical Systems, Munich, Germany).

  Baseline, 6 hours, one day, and 3 days

• Change of hemodynamic parameters (lung water: ELWI)

  Change from Baseline Extravascular lung water index (EVLWI; mL/kg) at 6 hours. Extravascular lung water index (EVLWI; mL/kg) will be calculated by the PiCCO device (Pulsion Medical Systems, Munich, Germany). EVLWI means total water in lung tissue, it increase in pulmonary edema or ARDS. PVPI means pulmonary vascular permeability and always high in ARDS (acute respiratory distress syndrome)

  Baseline, 6 hours

• Change of hemodynamic parameters (lung permeability: PVPI)

  Change from Baseline pulmonary vascular permeability index (PVPI; ratio) at 6 hours. pulmonary vascular permeability index (PVPI) will be calculated by the PiCCO device (Pulsion Medical Systems, Munich, Germany). EVLWI means total water in lung tissue, it increase in pulmonary edema or ARDS. PVPI means pulmonary vascular permeability and always high in ARDS (acute respiratory distress syndrome)

  Baseline, 6 hours

Secondary Outcomes (15)

• Autophagy biomarkers in exosomes: LC3II (Western blots)

  6 hours

• Autophagy biomarkers in exosomes: LC3II (NTA)

  6 hours

• Autophagy modifiers in exosomes: mTOR (Western blots)

  6 hours

• Autophagy modifiers in exosomes: mTOR (NTA)

  6 hours

• Autophagy modifiers in exosomes: HSP70 (Western blots)

  6 hours

Study Arms (2)

Sepsis with cardiopulmonary failure

Patient with sepsis and also respiratory and heart involvement, confirmed by Hemodynamic parameters

Diagnostic Test: Hemodynamic parameters

Sepsis without cardiopulmonary failure

Patient with sepsis without respiratory and heart involvement

Diagnostic Test: Hemodynamic parameters

Interventions

Hemodynamic parameters DIAGNOSTIC_TEST

Pulse contour cardiac output monitored heart contractility, end-diastolic volume parameters, and lung water parameters.

Sepsis with cardiopulmonary failure; Sepsis without cardiopulmonary failure

Eligibility Criteria

• Age: 20 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Sepsis was defined as a life-threatening organ dysfunction due to a dysregulated host response to infection. Patient with sepsis who was admitted to ICU. PiCCO hemodynamics was setted

You may qualify if:

• Patients with sepsis who admit to ICU
• Sepsis diagnostic criteria: acute change in total SOFA score ≥ 2 points attributable to infection
• Pulse indicator continuous cardiac output monitor (PiCCO) is accept by patient for hemodynamic monitoring

You may not qualify if:

• Patients with acute SOFA changes \< 2 points are excluded
• auria, no urine can be collected
• Previous cardiopulmonary co-morbidity. Chronic respiratory failure with ventilator dependence and chronic heart failure.

Sponsors & Collaborators

• Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation: lead

Study Sites (1)

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Taipei, 23142, Taiwan

Location

Related Publications (2)

• Lo S, Yuan SS, Hsu C, Cheng YJ, Chang YF, Hsueh HW, Lee PH, Hsieh YC. Lc3 over-expression improves survival and attenuates lung injury through increasing autophagosomal clearance in septic mice. Ann Surg. 2013 Feb;257(2):352-63. doi: 10.1097/SLA.0b013e318269d0e2.

  PMID: 22968077 BACKGROUND

• Gao M, Ha T, Zhang X, Wang X, Liu L, Kalbfleisch J, Singh K, Williams D, Li C. The Toll-like receptor 9 ligand, CpG oligodeoxynucleotide, attenuates cardiac dysfunction in polymicrobial sepsis, involving activation of both phosphoinositide 3 kinase/Akt and extracellular-signal-related kinase signaling. J Infect Dis. 2013 May 1;207(9):1471-9. doi: 10.1093/infdis/jit036. Epub 2013 Jan 28.

  PMID: 23359590 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood and urine, extract exosome collection

Study Officials

• Wen-Lin Su, PhD

  Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Taipei Tzu Chi Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2017
• First Posted: August 30, 2017
• Study Start: January 18, 2017
• Primary Completion: January 30, 2020
• Study Completion: January 30, 2020
• Last Updated: February 10, 2021

Record last verified: 2021-02

Locations

TW (1)