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

• Conditions: Sepsis; Multiple Organ Failure

• Registration Number: NCT02426645
• Lead Sponsor: Prof. Dr. Marc-H. Dahlke, Ph. D.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2015-04
• Study First Submitted: 2015-04-16
• Study First Submitted QC: 2015-04-21
• Study First Posted: 2015-04-27
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-04
• Last Update Posted: 2018-05-07
• Primary Completion: 2019-01
• Study Completion: 2019-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 25

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	60 weeks	Flow cytometry

Trial Locations

Locations (1)

Department of Surgery, University Hospital Regensburg; 🇩🇪 Regensburg, Bavaria, Germany