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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-000895-90 | EudraCT Number |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Continuous perfusion of esmolol | Experimental | Intervention: Drug: Continuous perfusion of esmolol |
|
| Continuous perfusion of saline | Placebo Comparator | Intervention: Continuous perfusion of saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Continuous perfusion of esmolol | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Is stroke volume increased ≥ 15% as compared to baseline? | 4 hours |
| Measure | Description | Time Frame |
|---|---|---|
| The time spent with a central venous oxygen saturation between 70% and 80% (minutes) | 4 hours | |
| Evolution of blood lactate between H0 and H4 | 4 hours | |
| Changes in tissue oxygen saturation compared to baseline |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc Leone, MD, PhD | Centre Hospitalier Universitaire de Nīmes | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| APHM - Hôpital Nord | Marseille | 13915 | France | |||
| CHRU de Nîmes - Hôpital Universitaire Carémeau |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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| Continuous perfusion of saline | Drug | 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. |
|
| 4 hours |
| Ejection fraction of the left ventricle drops below 40% between H0 and H4? yes/no | 4 hours |
| the change (in %) of the systolic S wave on the tissue doppler at the mitral annulus relative to baseline | 4 hours |
| Change (%) in the sub aortic time-speed integral relative to baseline | 4 hours |
| Absolute values of the E wave | baseline (hour 0) |
| Absolute values of the E wave | 4 hours |
| Absolute values of the E' wave | baseline (hour 0) |
| Absolute values of the E' wave | 4 hours |
| Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus | baseline (hour 0) |
| Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus | 4 hours |
| Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus | baseline (hour 0) |
| Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus | 4 hours |
| Right ventricular systolic function | baseline (hour 0) |
| Right ventricular systolic function | 4 hours |
| right ventricle / left ventricle diameter ratio | baseline (hour 0) |
| right ventricle / left ventricle diameter ratio | 4 hours |
| Vascular filling volume (ml) | 4 hours |
| Diuresis (ml/kg/h) | collected between hours 0 and 4 |
| Change in creatinine relative to baseline (µmol/L) | 4 hours |
| Required duration of vasopressors (min) | 4 hours |
| Use of positive ionotropic agents? yes/no | 4 hours |
| Percentage variation o, inflammatory cytokines (tissue necrosis factor) with respect to baseline values | 4 hours |
| Percentage variation o, inflammatory cytokines (interleukin 1) with respect to baseline values | 4 hours |
| Percentage variation o, inflammatory cytokines (interleukin 10) with respect to baseline values | 4 hours |
| Percentage change in the expression of the human leukocyte antigen-DR gene with respect to baseline | 4 hours |
| Length of stay in the intensive care unit (days) | The maximum observed length of stay in the intensive care unit (days) = Dmax | Expected maximum of 28 days |
| Number of days free of organ failure | Dmax +1 (Dmax has an expected maximum of 28 days) |
| Mortality | Dmax +1 (Dmax has an expected maximum of 28 days) |
| Nîmes |
| 30029 |
| France |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |