Clinical Trial: Effect of a Continuous Infusion of Esmolol on Stroke Volume in Patients With Hyperdynamic Vasoplegic Septic Shock

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Effect of a Continuous Infusion of Esmolol on Stroke Volume in Patients With Hyperdynamic Vasoplegic Septic Shock: a Multicentre, Randomized, Double-blind Trial

Brief Summary:

The main objective of this study is to evaluate the effectiveness of the administration of a short acting beta-blocker in terms of effective increase in stroke volume (at least 15%) after 4 hours initiation of therapy in septic shock in patients with a hyperkinetic profile after 12-24 hours of care.

This research seeks to demonstrate that the proportion of patients with an increase in the systolic ejection superior or equal to 15% (relative to baseline) at four hours is different between the two arms of the study: (1) an experimental arm where patients receive an esmolol infusion according to a predetermined procedure and (2) a control arm where patients receive a saline infusion according to a predetermined procedure.


Detailed Summary:

The secondary objectives are to compare the following items between the two arms of the study:

A. Central venous oxygen saturation at 4 hours (H4)

B. Changes in plasma concentration of lactates between H0 and H4

C. Changes in the tissue oxygen saturation between H0 and H4

D. Changes in echocardiographic parameters of systolic function of the left ventricle (LV) and right ventricle (RV), as well as diastolic LV function between H0 and H4

E. Vascular Filling volume during the study period

F. Kidney function: urine output and creatinine changes between H0 and H4

G. The required vasopressor time between H0 and H4

H. Use of positive inotropic agents

I. The inflammatory response via the analysis of HLA-DR between H0 and H4 and M1 / M2 responses at H4

J. The duration of ICU stay, mortality, morbidity in terms of organ failures


Sponsor: Centre Hospitalier Universitaire de Nīmes

Current Primary Outcome: Is stroke volume increased ≥ 15% as compared to baseline? [ Time Frame: 4 hours ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • The time spent with a central venous oxygen saturation between 70% and 80% (minutes) [ Time Frame: 4 hours ]
  • Evolution of blood lactate between H0 and H4 [ Time Frame: 4 hours ]
  • Changes in tissue oxygen saturation compared to baseline [ Time Frame: 4 hours ]
  • Ejection fraction of the left ventricle drops below 40% between H0 and H4? yes/no [ Time Frame: 4 hours ]
  • the change (in %) of the systolic S wave on the tissue doppler at the mitral annulus relative to baseline [ Time Frame: 4 hours ]
  • Change (%) in the sub aortic time-speed integral relative to baseline [ Time Frame: 4 hours ]
  • Absolute values of the E wave [ Time Frame: baseline (hour 0) ]
  • Absolute values of the E wave [ Time Frame: 4 hours ]
  • Absolute values of the E' wave [ Time Frame: baseline (hour 0) ]
  • Absolute values of the E' wave [ Time Frame: 4 hours ]
  • Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus [ Time Frame: baseline (hour 0) ]
  • Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus [ Time Frame: 4 hours ]
  • Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus [ Time Frame: baseline (hour 0) ]
  • Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus [ Time Frame: 4 hours ]
  • Right ventricular systolic function [ Time Frame: baseline (hour 0) ]
  • Right ventricular systolic function [ Time Frame: 4 hours ]
  • right ventricle / left ventricle diameter ratio [ Time Frame: baseline (hour 0) ]
  • right ventricle / left ventricle diameter ratio [ Time Frame: 4 hours ]
  • Vascular filling volume (ml) [ Time Frame: 4 hours ]
  • Diuresis (ml/kg/h) [ Time Frame: collected between hours 0 and 4 ]
  • Change in creatinine relative to baseline (µmol/L) [ Time Frame: 4 hours ]
  • Required duration of vasopressors (min) [ Time Frame: 4 hours ]
  • Use of positive ionotropic agents? yes/no [ Time Frame: 4 hours ]
  • Percentage variation o, inflammatory cytokines (tissue necrosis factor) with respect to baseline values [ Time Frame: 4 hours ]
  • Percentage variation o, inflammatory cytokines (interleukin 1) with respect to baseline values [ Time Frame: 4 hours ]
  • Percentage variation o, inflammatory cytokines (interleukin 10) with respect to baseline values [ Time Frame: 4 hours ]
  • Percentage change in the expression of the human leukocyte antigen-DR gene with respect to baseline [ Time Frame: 4 hours ]
  • Length of stay in the intensive care unit (days) [ Time Frame: Expected maximum of 28 days ]
    The maximum observed length of stay in the intensive care unit (days) = Dmax
  • Number of days free of organ failure [ Time Frame: Dmax +1 (Dmax has an expected maximum of 28 days) ]
  • Mortality [ Time Frame: Dmax +1 (Dmax has an expected maximum of 28 days) ]


Original Secondary Outcome: Same as current

Information By: Centre Hospitalier Universitaire de Nīmes

Dates:
Date Received: November 17, 2015
Date Started: July 2016
Date Completion: August 2018
Last Updated: April 6, 2016
Last Verified: April 2016