Clinical Trial: Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock

Brief Summary:

The purpose of this study is :

- to evaluate the hemodynamic tolerance of esmolol titrated to obtain a lowering of heart rate of 10% or 20%.


Detailed Summary:

During septic shock, the consequences of treatment by a β1-blocker on inflammation and cardiovascular variability are unknown. The use of esmolol should have positive effects on inflammation and hemodynamic tolerance. These effects are probably dose-dependent.

The study will enroll adult patients hospitalized in ICU, for severe septic shock requiring treatment by a vasopressor.

A total of 45 patients will be included. Among these 45 patients, 15 patients will be randomized in the control group. 30 patients will be randomized to Esmolol with the objective to decrease heart rate by 10% (Group G10, n=15) or 20% (Group G20, n=15). Esmolol will be administered for 24 hours.

This multicenter study will be performed in 3 investigation sites.

The following parameters will be evaluated at different moments during the 28 days follow up of each patient, mainly:

  • Origin of sepsis, SOFA score.
  • Hemodynamic parameters will be continuously recorded for the 24 hours of experimental period.
  • Cardiovascular variability (arterial pressure and heart rate) will be recorded for 24 hours.
  • 3 echocardiograms at H0, H12 and H24 will be performed.

  • Biological parameters will be sampled at H0, H6, H12 and H24: They include standard biological parameters (Urea, Creatinin, Bilirubin,……) and specific parameters (catecholamines, vasopressin, insulin, cortisol, proinflammatory cytokines and anti-inflammatory cytokines. Dosages will be performed only at H0, H12 and H24 in order to
    Sponsor: Assistance Publique - Hôpitaux de Paris

    Current Primary Outcome:

    • Comparison of hemodynamic parameters between 3 groups [ Time Frame: 24 hours ]

      3 groups: GC, G10 and G20.

      The hemodynamic tolerance will be considered as satisfactory if the variation of MAP and cardiac output induced by esmolol does not exceed 15% of baseline (H0).

    • Immunomodulatory effect [ Time Frame: 24 hours ]

      Immunomodulatory effect of esmolol will be evaluated notably by the ratio of IL6 / IL10.

      The decrease of this ratio in comparison with the value at baseline (H0) will be considered as an indicator of esmolol efficacy as immunomodulator.



    Original Primary Outcome:

    • Comparison of hemodynamic parameters between 3 groups [ Time Frame: 24 hours ]

      3 groups: GC, G10 and G20.

      The hemodynamic tolerance will be considered as satisfactory if the variation of MAP and cardiac output induced by esmolol does not exceed 15% of baseline (H0).

    • Immunomodulatory effect [ Time Frame: 24 hours ]

      Immunomodulatory effect of esmolol will be evaluated by the ratio of IL6 / IL10.

      The decrease of this ratio in comparison with the value at baseline (H0) will be considered as an indicator of esmolol efficacy as immunomodulator.



    Current Secondary Outcome:

    • Comparison of number and severity of organ failures, between the 3 groups [ Time Frame: 28 days ]
      3 groups will be evaluated by SOFA score.
    • Comparison of autonomic nervous system activity between the 3 groups [ Time Frame: 24 hours ]
      Power spectrum analysis of heart rate variability.
    • Comparison of mortality in the 3 groups [ Time Frame: 28 days ]
    • Comparison in the 3 groups of the correlations between the biomarkers and the hemodynamic data [ Time Frame: 24 hours ]
      The biomarkers in plasma levels: cortisol, catecholamine, proinflammatory cytokines and anti-inflammatory cytokines.


    Original Secondary Outcome: Same as current

    Information By: Assistance Publique - Hôpitaux de Paris

    Dates:
    Date Received: April 18, 2014
    Date Started: April 2015
    Date Completion: May 2017
    Last Updated: May 22, 2017
    Last Verified: April 2017