Clinical trial NCT02426645: Microcirculatory Alteration and Biomarkers: New Approach for Early Assessment of Septic Multi-organ Dysfunction
Official title: Microcirculatory Alteration and Biomarkers: New Approach for Early Assessment of Septic Multi-organ Dysfunction
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sepsis
Multiple Organ Failure
Keywords: Biomarkers
Sepsis
Multi organ dysfunction
Immunomonitoring
CEUS
Lead sponsor: University Hospital Regensburg
Sponsor class: OTHER
First posted: 2015-04-27
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with severe sepsis of abdominal origin within 24h after onset and performed source control

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 60 weeks
Secondary outcomes:
measure: 28 day mortality
timeFrame: 60 weeks
measure: 90 day mortality
timeFrame: 60 weeks
measure: Length of ICU stay
timeFrame: 60 weeks
measure: Length of hospital stay
timeFrame: 60 weeks
measure: Early post-operative course of microvascular perfusion of the kidney and muscle vasculature bed using CEUS
timeFrame: 60 weeks
measure: Incidence of acute kidney injury (AKI) within the first 48 hours as based on current Kidney Disease: Improving Global Outcomes (KDIGO) recommendation
timeFrame: 60 weeks
measure: Incidence of acute kidney injury (AKI) within the first 7 days as based on current Kidney Disease: Improving Global Outcomes (KDIGO) recommendation
timeFrame: 60 weeks
measure: Need for renal replacement therapy (RRT) after admission to ICU
timeFrame: 60 weeks
measure: Identification of an "immunological fingerprint" indicating multi-organ dysfunction
timeFrame: 60 weeks
Other outcomes:
Locations:
city: Regensburg
country: Germany
facility: Department of Surgery, University Hospital Regensburg
state: Bavaria
Study officials:
affiliation: University Hospital Regensburg
name: Marc H Dahlke, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: