Microcirculatory Alteration and Biomarkers: New Approach for Early Assessment of Septic Multi-organ Dysfunction

The aim of this study is to investigate associations between early structural cellular injury and microvascular alteration with progression of septic organ dysfunction according to total SOFA-Score (an ICU-scoring system - the Sequential Organ Failure Assessment Score). Patients will be monitored for renal (TIMP-2, IGFBP7), and intestinal biomarkers (plasma i-FABP) in conjunction with kidney and muscle vascular bed microvascular perfusion analysis assessed by contrast-enhanced ultrasonography (CEUS). In parallel, a comprehensive analysis of patients' immunological status will be conducted using an established, on-site immune monitoring panel.

The ultimate goal of this study is an early identification of septic patients developing multiorgan dysfunction which may facilitate a timely novel intervention in the future to improve outcome.

Study Overview

• Status: Unknown
• Conditions: Sepsis; Multiple Organ Failure

• Study Type: Observational
• Enrollment (Anticipated): 25

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Department of Surgery, University Hospital Regensburg

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: Non-Probability Sample

Study Population

Adult patients with severe sepsis of abdominal origin within 24h after onset and performed source control

Description

Inclusion Criteria:

Patients ≥18 years of age with severe sepsis and fulfill the following criteria at the admission to ICU:

• Peritonitis (abdominal infection) and performed source control (either surgically or interventionally)
• 2 or more criteria for systemic inflammatory response syndrome (temperature >38° or<36°; heart rate >90 beats per minute; respiratory rate >20 breaths per minute or paCO2 <32 mmHg; white blood cell count >12,000/mm3, <4000mm3 or >10% immature forms) and serum lactate level of 4mmol/l and more or refractory hypotension - mean arterial pressure <65mmHg or systolic blood pressure <90mmHg after fluid challenge of 1000ml or more /30min
• Absence of any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Written informed consent prior to any study procedures

Exclusion Criteria:

• Pre-existing renal-replacement therapy in the pre-operative course
• Pre-existing shock
• Acute coronary syndrome
• Active hemorrhage
• Trauma
• Known allergy to ultrasound contrast media
• Anemia with hemoglobin concentration < 7g/dl
• Patients not able to give written informed consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Assessment of early post-operative course of novel cellular injury biomarkers as well as microvascular perfusion in critically ill patients with severe sepsis and to collection any first evidence of the association of these markers with the SOFA-Score	60 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
28 day mortality		60 weeks
90 day mortality		60 weeks
Length of ICU stay		60 weeks
Length of hospital stay		60 weeks
Early post-operative course of microvascular perfusion of the kidney and muscle vasculature bed using CEUS		60 weeks
Incidence of acute kidney injury (AKI) within the first 48 hours as based on current Kidney Disease: Improving Global Outcomes (KDIGO) recommendation		60 weeks
Incidence of acute kidney injury (AKI) within the first 7 days as based on current Kidney Disease: Improving Global Outcomes (KDIGO) recommendation		60 weeks
Need for renal replacement therapy (RRT) after admission to ICU		60 weeks
Identification of an "immunological fingerprint" indicating multi-organ dysfunction	Flow cytometry	60 weeks

Collaborators and Investigators

• Sponsor: Prof. Dr. Marc-H. Dahlke, Ph. D.
• Investigators: Principal Investigator: Marc H Dahlke, Prof. Dr., University Hospital Regensburg

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): April 1, 2019

Study Registration Dates

• First Submitted: April 16, 2015
• First Submitted That Met QC Criteria: April 21, 2015
• First Posted (Estimate): April 27, 2015

Study Record Updates

• Last Update Posted (Actual): May 7, 2018
• Last Update Submitted That Met QC Criteria: May 4, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Biomarkers; Sepsis; CEUS; Immunomonitoring; Multi organ dysfunction
• Additional Relevant MeSH Terms: Pathologic Processes; Shock; Multiple Organ Failure
• Other Study ID Numbers: Mibisep