Back to resultsEffect of a Continuous Infusion of Esmolol on Stroke Volume in Patients With Hyperdynamic Vasoplegic Septic Shock (BétaSep)
Primary Purpose
Shock, Septic
Status
Withdrawn
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Continuous perfusion of esmolol
Continuous perfusion of saline
Sponsored by
About this trial
This is an interventional treatment trial for Shock, Septic
Eligibility Criteria
Inclusion Criteria:
- The patient or his/her representative was informed about the implementation of the study, its objectives, constraints and patient rights or emergency consent
- The patient or his/her representative must haven given free and informed consent and signed the consent or emergency consent
- The patient must be affiliated with or the recipient of a health insurance plan
- Septic shock criteria: shock for which the suspected or proven starting point is an infection requiring vasopressors after adequate fluid resuscitation that started within the past 24 to 72 hours
- Precharge independence criteria obtained: i.e. pulsed pressure variation <13% or variation in ejection volume <10% or variation in the cardiac index after passive lift leg <10% or central venous pressure between 8 and 12 mmHg.
- Antibiotic treatment in progress
- Prescription ongoing vasopressor for 24 to 72 hours.
- Sinus rhythm
- Heart rate > 100 beats per minute
- Cardiac Index measured by thermodilution greater than 4.0 l / min / m^2
- Central venous oxygen saturation > 80% without positive inotropics such as dobutamine or isoproterenol (continuously taken or measured via central venous line in superior vena cava territory) on two successive samples in 12 hours
- Monitoring of stroke volume (invasive, semi-invasive or ultrasound)
Exclusion Criteria:
- The patient is participating in another study
- The patient has participated in another study in the last 3 months
- The patient is in an exclusion period determined by a previous study
- The patient is under any kind of guardianship
- The patient is under judicial protection
- The patient or his/her representative refuses to sign the consent
- It is impossible to correctly inform the patient
- The patient is pregnant, parturient, or breastfeeding
- The patient has a contraindication for a treatment used in this study
- Cardiac index < 4.0 l / min / m^2
- Need to introduce a positive inotropic agent (as determined by the physician in charge of the patient)
- Contraindications to the use of esmolol: Severe sinus bradycardia (less than 50 beats per minute); Sinus pathologies, severe disorders of atrioventricular conduction (without pacemaker), atrioventricular blocks of second and third degree; Cardiogenic shock; Severe hypotension; Decompensated heart failure; Untreated pheochromocytoma; Pulmonary hypertension; Acute asthma attack; chronic obstructive pulmonary disease; peripheral arterial disease; Metabolic acidosis; Known hypersensitivity to esmolol.
- Patient with kidney failure (RIFLE Stage L)
- Chronic treatment with beta blocker
- Patient with ultrasound assessment of left ventricular ejection fraction < 40%
Sites / Locations
- APHM - Hôpital Nord
- CHRU de Nîmes - Hôpital Universitaire Carémeau
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Continuous perfusion of esmolol
Continuous perfusion of saline
Arm Description
Intervention: Drug: Continuous perfusion of esmolol
Intervention: Continuous perfusion of saline
Outcomes
Primary Outcome Measures
Is stroke volume increased ≥ 15% as compared to baseline?
Secondary Outcome Measures
The time spent with a central venous oxygen saturation between 70% and 80% (minutes)
Evolution of blood lactate between H0 and H4
Changes in tissue oxygen saturation compared to baseline
Ejection fraction of the left ventricle drops below 40% between H0 and H4? yes/no
the change (in %) of the systolic S wave on the tissue doppler at the mitral annulus relative to baseline
Change (%) in the sub aortic time-speed integral relative to baseline
Absolute values of the E wave
Absolute values of the E wave
Absolute values of the E' wave
Absolute values of the E' wave
Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus
Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus
Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus
Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus
Right ventricular systolic function
Right ventricular systolic function
right ventricle / left ventricle diameter ratio
right ventricle / left ventricle diameter ratio
Vascular filling volume (ml)
Diuresis (ml/kg/h)
Change in creatinine relative to baseline (µmol/L)
Required duration of vasopressors (min)
Use of positive ionotropic agents? yes/no
Percentage variation o, inflammatory cytokines (tissue necrosis factor) with respect to baseline values
Percentage variation o, inflammatory cytokines (interleukin 1) with respect to baseline values
Percentage variation o, inflammatory cytokines (interleukin 10) with respect to baseline values
Percentage change in the expression of the human leukocyte antigen-DR gene with respect to baseline
Length of stay in the intensive care unit (days)
The maximum observed length of stay in the intensive care unit (days) = Dmax
Number of days free of organ failure
Mortality
Full Information
NCT ID
NCT02609152
First Posted
November 17, 2015
Last Updated
May 14, 2018
Sponsor
Centre Hospitalier Universitaire de Nīmes
1. Study Identification
Unique Protocol Identification Number
NCT02609152
Brief Title
Effect of a Continuous Infusion of Esmolol on Stroke Volume in Patients With Hyperdynamic Vasoplegic Septic Shock
Acronym
BétaSep
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Withdrawn
Why Stopped
logistical difficulties
Study Start Date
July 2016 (Anticipated)
Primary Completion Date
July 2017 (Anticipated)
Study Completion Date
August 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nīmes
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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 Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Shock, Septic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Continuous perfusion of esmolol
Arm Type
Experimental
Arm Description
Intervention: Drug: Continuous perfusion of esmolol
Arm Title
Continuous perfusion of saline
Arm Type
Placebo Comparator
Arm Description
Intervention: Continuous perfusion of saline
Intervention Type
Drug
Intervention Name(s)
Continuous perfusion of esmolol
Intervention Description
In the experimental arm of the study, a continuous perfusion of esmolol will be performed. This infusion starts at 5 ml / h with an increase of 5 ml / hr every 10 minutes to obtain a 15% decrease in heart rate. The infusion will be reduced by 5 ml / h every 5 minutes if the cardiac rate is less than 90 beats per minute and stopped if it is less than 70 beats per minute. At H4, the doctor in charge is free to gradually continue or stop the infusion.
Intervention Type
Drug
Intervention Name(s)
Continuous perfusion of saline
Intervention Description
In the control arm of the study, a continuous infusion of normal saline will be performed. This infusion starts at 5 ml / h with an increase of 5 ml / hr every 10 minutes to obtain a 15% decrease in heart rate. The infusion will be reduced by 5 ml / h every 5 minutes if the cardiac rate is less than 90 beats per minute and stopped if it is less than 70 beats per minute. A H4, the doctor in charge is free to gradually continue or stop the infusion.
Primary Outcome Measure Information:
Title
Is stroke volume increased ≥ 15% as compared to baseline?
Time Frame
4 hours
Secondary Outcome Measure Information:
Title
The time spent with a central venous oxygen saturation between 70% and 80% (minutes)
Time Frame
4 hours
Title
Evolution of blood lactate between H0 and H4
Time Frame
4 hours
Title
Changes in tissue oxygen saturation compared to baseline
Time Frame
4 hours
Title
Ejection fraction of the left ventricle drops below 40% between H0 and H4? yes/no
Time Frame
4 hours
Title
the change (in %) of the systolic S wave on the tissue doppler at the mitral annulus relative to baseline
Time Frame
4 hours
Title
Change (%) in the sub aortic time-speed integral relative to baseline
Time Frame
4 hours
Title
Absolute values of the E wave
Time Frame
baseline (hour 0)
Title
Absolute values of the E wave
Time Frame
4 hours
Title
Absolute values of the E' wave
Time Frame
baseline (hour 0)
Title
Absolute values of the E' wave
Time Frame
4 hours
Title
Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus
Time Frame
baseline (hour 0)
Title
Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus
Time Frame
4 hours
Title
Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus
Time Frame
baseline (hour 0)
Title
Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus
Time Frame
4 hours
Title
Right ventricular systolic function
Time Frame
baseline (hour 0)
Title
Right ventricular systolic function
Time Frame
4 hours
Title
right ventricle / left ventricle diameter ratio
Time Frame
baseline (hour 0)
Title
right ventricle / left ventricle diameter ratio
Time Frame
4 hours
Title
Vascular filling volume (ml)
Time Frame
4 hours
Title
Diuresis (ml/kg/h)
Time Frame
collected between hours 0 and 4
Title
Change in creatinine relative to baseline (µmol/L)
Time Frame
4 hours
Title
Required duration of vasopressors (min)
Time Frame
4 hours
Title
Use of positive ionotropic agents? yes/no
Time Frame
4 hours
Title
Percentage variation o, inflammatory cytokines (tissue necrosis factor) with respect to baseline values
Time Frame
4 hours
Title
Percentage variation o, inflammatory cytokines (interleukin 1) with respect to baseline values
Time Frame
4 hours
Title
Percentage variation o, inflammatory cytokines (interleukin 10) with respect to baseline values
Time Frame
4 hours
Title
Percentage change in the expression of the human leukocyte antigen-DR gene with respect to baseline
Time Frame
4 hours
Title
Length of stay in the intensive care unit (days)
Description
The maximum observed length of stay in the intensive care unit (days) = Dmax
Time Frame
Expected maximum of 28 days
Title
Number of days free of organ failure
Time Frame
Dmax +1 (Dmax has an expected maximum of 28 days)
Title
Mortality
Time Frame
Dmax +1 (Dmax has an expected maximum of 28 days)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The patient or his/her representative was informed about the implementation of the study, its objectives, constraints and patient rights or emergency consent
The patient or his/her representative must haven given free and informed consent and signed the consent or emergency consent
The patient must be affiliated with or the recipient of a health insurance plan
Septic shock criteria: shock for which the suspected or proven starting point is an infection requiring vasopressors after adequate fluid resuscitation that started within the past 24 to 72 hours
Precharge independence criteria obtained: i.e. pulsed pressure variation <13% or variation in ejection volume <10% or variation in the cardiac index after passive lift leg <10% or central venous pressure between 8 and 12 mmHg.
Antibiotic treatment in progress
Prescription ongoing vasopressor for 24 to 72 hours.
Sinus rhythm
Heart rate > 100 beats per minute
Cardiac Index measured by thermodilution greater than 4.0 l / min / m^2
Central venous oxygen saturation > 80% without positive inotropics such as dobutamine or isoproterenol (continuously taken or measured via central venous line in superior vena cava territory) on two successive samples in 12 hours
Monitoring of stroke volume (invasive, semi-invasive or ultrasound)
Exclusion Criteria:
The patient is participating in another study
The patient has participated in another study in the last 3 months
The patient is in an exclusion period determined by a previous study
The patient is under any kind of guardianship
The patient is under judicial protection
The patient or his/her representative refuses to sign the consent
It is impossible to correctly inform the patient
The patient is pregnant, parturient, or breastfeeding
The patient has a contraindication for a treatment used in this study
Cardiac index < 4.0 l / min / m^2
Need to introduce a positive inotropic agent (as determined by the physician in charge of the patient)
Contraindications to the use of esmolol: Severe sinus bradycardia (less than 50 beats per minute); Sinus pathologies, severe disorders of atrioventricular conduction (without pacemaker), atrioventricular blocks of second and third degree; Cardiogenic shock; Severe hypotension; Decompensated heart failure; Untreated pheochromocytoma; Pulmonary hypertension; Acute asthma attack; chronic obstructive pulmonary disease; peripheral arterial disease; Metabolic acidosis; Known hypersensitivity to esmolol.
Patient with kidney failure (RIFLE Stage L)
Chronic treatment with beta blocker
Patient with ultrasound assessment of left ventricular ejection fraction < 40%
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Leone, MD, PhD
Organizational Affiliation
Centre Hospitalier Universitaire de Nîmes
Official's Role
Study Director
Facility Information:
Facility Name
APHM - Hôpital Nord
City
Marseille Cedex 20
ZIP/Postal Code
13915
Country
France
Facility Name
CHRU de Nîmes - Hôpital Universitaire Carémeau
City
Nîmes Cedex 09
ZIP/Postal Code
30029
Country
France
12. IPD Sharing Statement
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Effect of a Continuous Infusion of Esmolol on Stroke Volume in Patients With Hyperdynamic Vasoplegic Septic Shock
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