Effects of Acute Systemic Inflammation on Arterial Stiffness and Microcirculation. (IRIGA)

This study aims to assess the effect of acute inflammation on arterial stiffness and microcirculation. Patients with severe sepsis will be compared with age-, sex- and cardiovascular risk factors-matched controls.

The primary outcome is the carotid-femoral pulse wave velocity. The other outcome measures are: systemic hemodynamics (systolic, diastolic, mean and pulse blood pressures, heart rate, cardiac output, left ventricular ejection fraction, systemic vascular resistances), central hemodynamics (aortic systolic, diastolic, mean and pulse pressures, and augmentation index), thenar tissue oxygen saturation, biological makers of inflammation (plasma fibrinogen, C-reactive protein, interleukin-6, matrix metalloproteinases -2, -9, tissue inhibitor of metalloproteinase 1), and plasma catecholamine concentrations (epinephrine, norepinephrine).

Study Overview

• Status: Completed
• Conditions: Severe Sepsis
• Intervention / Treatment: Other: NA : non interventional study

Detailed Description

In a model of acute inflammation induced by salmonella typhi vaccination in healthy volunteers, it has been shown that acute systemic inflammation increased arterial stiffness. Since increased arterial stiffness (assessed by carotid-femoral pulse wave velocity) is an independent prognosis marker of cardiovascular risk in many chronic diseases such as hypertension, renal failure or diabetes mellitus, it could also be a marker of severity in acute inflammation states. Severe sepsis is a leading cause of hospitalisation in intensive care units, and constitutes a state of acute inflammation. It remains however to confirm that arterial stiffness is increased in this clinical conditions before evaluating its prognosis value.

This study aims to assess the effect of severe sepsis on arterial stiffness and microcirculation. Patients with severe sepsis will be compared with age-, sex- and cardiovascular risk factors-matched controls.

The primary outcome is the carotid-femoral pulse wave velocity. The other outcome measures are: systemic hemodynamics (systolic, diastolic, mean and pulse blood pressures, heart rate, cardiac output, left ventricular ejection fraction, systemic vascular resistances), central hemodynamics (aortic systolic, diastolic, mean and pulse pressures, and augmentation index), thenar tissue oxygen saturation, biological makers of inflammation (plasma fibrinogen, C-reactive protein, interleukin-6, matrix metalloproteinases -2, -9, tissue inhibitor of metalloproteinase 1), and plasma catecholamine concentrations (epinephrine, norepinephrine).

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• France
  • Rennes, France, 35033
    • Unité d'Investigation Clinique - Hôpital de Pontchaillou
  • Rennes, France, 35033
    • Service de Réanimation Chirurgicale - Hôpital de Pontchaillou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

20 patients with severe sepsis. 20 controls matched on age, sex and cardiovascular risk factors .

Description

Inclusion Criteria:

• Control group :

  • male or female aged at least 18 years, matched on age, sex and cardiovascular risk factors (smoking, hypertension, diabetes and treated dyslipidemia) with septic patients
  • Normal clinical examination and normal 12-lead ECG
  • Routines biological tests in the normal range of the laboratories.
  • Body mass index between 18 and 27 kg/m²
  • Written informed consent

• Patients group :

  • Male or female aged at least 18 years

  • Severe sepsis defined by the presence of:

    • a systemic inflammatory response syndrome
    • the evidence of an infection
    • the presence of at least one organ failure or signs of tissue hypoperfusion.
  • Body mass index between 18 and 27 Kg/m²
  • Written informed consent from the patients or their relatives

Exclusion Criteria:

• Control group :

  • legal protection or persons deprived of liberty
  • bacterial or viral infection in the month preceding inclusion
  • current medication
  • pregnancy or breastfeeding
  • exclusion period stated on the national register for persons who participate to biomedical research

• Patients group :

  • legal protection or persons deprived of liberty
  • vasopressor therapy
  • bacterial or viral infection in the month preceding inclusion
  • known cardiomyopathy
  • pregnancy or breastfeeding

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
severe sepsis; patients with severe sepsis	Other: NA : non interventional study; NA : non interventional study
Controls; Controls matched to patients on age, sex and cardiovascular risk factors	Other: NA : non interventional study; NA : non interventional study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Carotid-femoral pulse wave velocity	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic hemodynamics	Systolic, diastolic, mean, and pulse blood pressures, and heart rate; Cardiac output, left ventricular ejection fraction, systemic vascular resistances	1 day
Central aortic hemodynamic	Aortic systolic, diastolic, mean and pulse pressures,; Augmentation index	1 day
Micro-circulation	Thenar tissue oxygen saturation	1 day
Biological markers from plasma samples	fibrinogen; C-reactiv protein; Interleukin-6; matrix metalloproteinases -2, -9, and tissue inhibitor of metalloproteinase 1; epinephrine and norepinephrine	1 day

Collaborators and Investigators

• Sponsor: Rennes University Hospital
• Investigators: Principal Investigator: Bruno LAVIOLLE, MD, PhD, Rennes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2012
• Primary Completion (Actual): April 16, 2015
• Study Completion (Actual): April 16, 2015

Study Registration Dates

• First Submitted: February 23, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (Estimate): March 16, 2012

Study Record Updates

• Last Update Posted (Actual): December 27, 2019
• Last Update Submitted That Met QC Criteria: December 26, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: arterial stiffness; Carotid-femoral pulse wave velocity; acute systemic inflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Sepsis; Inflammation
• Other Study ID Numbers: 2010-A00612-37