Presepsin:Gelsolin Ratio in Sepsis-related Organ Dysfunction

Sepsis Clinical Trial

Official title:

Presepsin:Gelsolin Ratio, as a Promising Marker of Sepsis-related Organ Dysfunction: a Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05060679
• Other study ID #: 4327.316-2900/KK15/2011
• Status: Completed
• Start date: January 1, 2018
• Est. completion date: February 29, 2020

Study information

• Verified date: March 2022
• Source: University of Pecs
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In the present study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. Exclusion criteria were patients under 18 years of age, unobtainable consent, end-stage renal disease requiring chronic dialysis or kidney transplantation and patients with malignancies needing palliative care. Not more than one sample (venous blood) was collected from control patients. Plasma presepsin levels were determined by an automated chemiluminescence-based Point of Care instrument while serum gelsolin levels were measured using an automated immune turbidimetric assay. Plasma presepsin concentrations were expressed as pg/mL, while serum gelsolin levels were expressed as mg/L. Data were compared with laboratory and clinical parameters. Patients were categorized by the Sepsis-3 definitions and 10-day mortality data were investigated. Presepsin:gelsolin ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic disturbances, respiratory insufficiency and acute kidney injury (AKI).

Description:

Presepsin is the 13-kDa soluble N-terminal fragment of the 55-kDa cluster of differentiation (CD) marker protein CD14, which is the receptor for lipopolysaccharide (LPS) and LPS-binding protein complexes. CD14 is a glycoprotein expressed mostly on the membrane surface of macrophages, monocytes and granulocytes which is released and degraded during inflammation after the recognition of pathogen-associated molecular patterns (PAMP), thus probably resulting in earlier elevation of plasma presepsin (PSEP) levels than the conventional sepsis biomarkers (C-reactive protein, procalcitonin). There is a growing body of evidence indicating increasing PSEP levels as kidney function decreases (e.g. during chronic kidney disease or sepsis-related AKI). Gelsolin (GSN) is a multifunctional protein existing in three different isoforms. Secreted or plasma GSN (MW = 83 kDa) is an essential component of the so-called extracellular actin scavenger system, therefore, decreasing serum GSN levels were reported in various clinical conditions (e.g. severe sepsis, multiple organ dysfunction syndrome (MODS), extensive trauma, acute liver failure, myocardial infarction). As albumin levels also tend to decrease in severe catabolic conditions, the simultaneous measurement of PSEP and GSN could prove to be useful regarding the diagnosis and prognosis of sepsis and sepsis-related organ dysfunction. Therefore, a new potential marker was investigated: the presepsin:gelsolin (PSEP:GSN) ratio. The main focuses of this study were analyzing the time course of PSEP:GSN ratio in non-septic and septic patients, while also investigating its diagnostic and prognostic utility in various sepsis-related organ dysfunctions in contrast to the conventional sepsis markers and clinical prognostic scores.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: February 29, 2020
• Est. primary completion date: February 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Non-septic patients needing ICU supportive treatment after major surgical interventions

• Sepsis

• Sepsis-related organ dysfunction (e.g. acute kidney injury, hemodynamic instability, acute respiratory distress syndrome)

Exclusion Criteria:

• under 18 years of age

• unobtainable consent

• end-stage renal disease

• kidney transplantation

• malignancies needing palliative care

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Kidney Injury Due to Sepsis
• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Sepsis
• Septic Shock
• Toxemia

Intervention

Other:
• Supportive therapy at the ICU
Non-septic ICU patients received adequate supportive treatment (fluid resuscitation, respiratory, anticoagulation, antimicrobial and vasopressor therapy along with sedation, ulcer prophylaxis and nutrition. Blood sampling for non-septic patients were the first (T1) and third (T3) postoperative morning at the ICU. Besides, 23 healthy outpatients were documented without sepsis or sepsis-related organ dysfuntion as a control group.
• Sepsis therapy
Patients receiving sepsis therapy followed the international guidelines of the 2016 Surviving Sepsis Campaign (SSC) regarding respiratory, antimicrobial, anticoagulation, vasopressor and hydrocortisone therapy, along with adequate fluid resuscitation, sedation, ulcer prophylaxis and nutrition. Blood samples were collected at the ICU from this patient group at three time points (T1-3): T1: within 12 hours after admission; T2: second day morning; T3: third day morning of follow-up.
• Sepsis-related organ dysfunction therapy
Patient management of sepsis and sepsis-related organ dysfunction followed the international guidelines of the 2016 Surviving Sepsis Campaign (SSC) regarding respiratory, antimicrobial, anticoagulation, vasopressor and hydrocortisone therapy, along with adequate fluid resuscitation, sedation, ulcer prophylaxis, nutrition and renal replacement therapy (if needed). In this patient group, blood sampling was performed at three time points (T1-3): T1: within 12 hours after admission; T2: second day morning; T3: third day morning of follow-up.

Locations

Country	Name	City	State
Hungary	Department of Anesthesiology and Intensive Therapy, Medical School, University of Pécs	Pécs	Baranya

Sponsors (1)

Lead Sponsor	Collaborator
University of Pecs

Country where clinical trial is conducted

Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma Presepsin concentrations	Plasma samples were centrifuged (10 min, 1500 g), then sample aliquots were stored without preservatives at -70 °C until analysis. Plasma presepsin levels were measured using an automated Point of Care instrument (PATHFAST; LSI Medience Corporation, Tokyo, Japan) based on a chemiluminescent enzyme immunoassay.	3 days
Primary	Serum gelsolin concentrations	Clotted blood samples were centrifuged (10 min, 1500 g), then sample aliquots were stored without preservatives at -70 °C until analysis. Serum gelsolin levels were determined with an automated immune turbidimetric assay (Cobas 8000/c502 module (Roche Diagnostics GmbH, Mannheim, Germany)).	3 days
Secondary	Presepsin:gelsolin ratios	Plasma presepsin levels were determined by an automated Point of Care instrument, while serum gelsolin concentrations were measured using an immune turbidimetric assay, therefore Presepsin:gelsolin ratios could be calculated.	5 days