Shock, SepticPhase 3BétaSepNCT02609152
Effect of a Continuous Infusion of Esmolol on Stroke Volume in Patients With Hyperdynamic Vasoplegic Septic Shock
A Phase 3 study testing Continuous perfusion of esmolol and Continuous perfusion of saline in people with Shock, Septic, run by Centre Hospitalier Universitaire de Nīmes at 2 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Shock, Septic
- What is being tested?
- Continuous perfusion of esmolol and Continuous perfusion of saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 2 sitesFrance
- Study dates
- Jul 2016to Aug 2017
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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
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- 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%
Trial locations and contacts
2 sites in 1 country.
France2 sites
APHM - Hôpital Nord
Marseille, 13915
CHRU de Nîmes - Hôpital Universitaire Carémeau
Nîmes, 30029
About this study
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
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.
Read the detailed description
The secondary objectives are to compare the following items between the two arms of the study:
- Central venous oxygen saturation at 4 hours (H4)
- Changes in plasma concentration of lactates between H0 and H4
- Changes in the tissue oxygen saturation between H0 and H4
- 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
- Vascular Filling volume during the study period
- Kidney function: urine output and creatinine changes between H0 and H4
- The required vasopressor time between H0 and H4
- Use of positive inotropic agents
- The inflammatory response via the analysis of HLA-DR between H0 and H4 and M1 / M2 responses at H4
- The duration of ICU stay, mortality, morbidity in terms of organ failures
- Conditions
- Shock, Septic
- Being tested
- Continuous perfusion of esmolol, Continuous perfusion of saline
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous perfusion of esmololDrug
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.
Continuous perfusion of salineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Continuous perfusion of esmolol | Experimental | Intervention: Drug: Continuous perfusion of esmolol Receives: Drug: Continuous perfusion of esmolol |
| Continuous perfusion of saline | Placebo comparator | Intervention: Continuous perfusion of saline Receives: Drug: Continuous perfusion of saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Is stroke volume increased ≥ 15% as compared to baseline?
Measured: 4 hours
Secondary outcomes (30)
The time spent with a central venous oxygen saturation between 70% and 80% (minutes)
Measured: 4 hours
Evolution of blood lactate between H0 and H4
Measured: 4 hours
Changes in tissue oxygen saturation compared to baseline
Measured: 4 hours
Ejection fraction of the left ventricle drops below 40% between H0 and H4? yes/no
Measured: 4 hours
the change (in %) of the systolic S wave on the tissue doppler at the mitral annulus relative to baseline
Measured: 4 hours
Change (%) in the sub aortic time-speed integral relative to baseline
Measured: 4 hours
Absolute values of the E wave
Measured: baseline (hour 0)
Absolute values of the E wave
Measured: 4 hours
Absolute values of the E' wave
Measured: baseline (hour 0)
Absolute values of the E' wave
Measured: 4 hours
Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus
Measured: baseline (hour 0)
Absolute value of the ratio E/A on pulsed Doppler at the mitral annulus
Measured: 4 hours
Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus
Measured: baseline (hour 0)
Absolute Value of the ratio E/E ' one tissue Doppler at the mitral annulus
Measured: 4 hours
Right ventricular systolic function
Measured: baseline (hour 0)
Right ventricular systolic function
Measured: 4 hours
right ventricle / left ventricle diameter ratio
Measured: baseline (hour 0)
right ventricle / left ventricle diameter ratio
Measured: 4 hours
Vascular filling volume (ml)
Measured: 4 hours
Diuresis (ml/kg/h)
Measured: collected between hours 0 and 4
Change in creatinine relative to baseline (µmol/L)
Measured: 4 hours
Required duration of vasopressors (min)
Measured: 4 hours
Use of positive ionotropic agents? yes/no
Measured: 4 hours
Percentage variation o, inflammatory cytokines (tissue necrosis factor) with respect to baseline values
Measured: 4 hours
Percentage variation o, inflammatory cytokines (interleukin 1) with respect to baseline values
Measured: 4 hours
Percentage variation o, inflammatory cytokines (interleukin 10) with respect to baseline values
Measured: 4 hours
Percentage change in the expression of the human leukocyte antigen-DR gene with respect to baseline
Measured: 4 hours
Length of stay in the intensive care unit (days)
The maximum observed length of stay in the intensive care unit (days) = Dmax
Measured: Expected maximum of 28 days
Number of days free of organ failure
Measured: Dmax +1 (Dmax has an expected maximum of 28 days)
Mortality
Measured: Dmax +1 (Dmax has an expected maximum of 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2015 (estimated)
- Study startJul 2016 (estimated)
- Primary completionJul 2017 (estimated)
- Study completionAug 2017 (estimated)
Why it stopped: logistical difficulties
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Shock, SepticStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NīmesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nīmes
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marc Leone, MD, PhD, Study director, Centre Hospitalier Universitaire de Nīmes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02609152
- Sponsor's protocol ID
- LOCAL/2014/ML-01
- Other IDs
- 2015-000895-90, 2015
- Acronym
- BétaSep
- Status last verified
- May 2018
- First submitted
- 17 Nov 2015
- Last updated
- 17 May 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02609152
- Acronym / sponsor ID
- BétaSep / LOCAL/2014/ML-01
- Conditions
- Shock, Septic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: logistical difficulties
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NīmesUniversity, hospital or other
- Study start
- Jul 2016 (estimated)
- Primary completion
- Jul 2017 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 20 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Central venous oxygen saturation at 4 hours (H4)
- Changes in plasma concentration of lactates between H0 and H4
- Changes in the tissue oxygen saturation between H0 and H4
- 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
- Vascular Filling volume during the study period
- Kidney function: urine output and creatinine changes between H0 and H4
- The required vasopressor time between H0 and H4
- Use of positive inotropic agents
- The inflammatory response via the analysis of HLA-DR between H0 and H4 and M1 / M2 responses at H4
- The duration of ICU stay, mortality, morbidity in terms of organ failures
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous perfusion of esmolol | Experimental | Drug: Continuous perfusion of esmololIntervention: Drug: Continuous perfusion of esmolol |
| Continuous perfusion of saline | Placebo comparator | Drug: Continuous perfusion of salineIntervention: Continuous perfusion of saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuous perfusion of esmololIn 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. | Drug | Continuous perfusion of esmolol |
| Continuous perfusion of salineIn 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. | Drug | Continuous perfusion of saline |
Primary outcome
Is stroke volume increased ≥ 15% as compared to baseline?
Time frame: 4 hours
30 secondary outcomes
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
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)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Leone, MD, PhD study director
Centre Hospitalier Universitaire de Nīmes
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Continuous perfusion of esmolol and Continuous perfusion of saline in people with Shock, Septic, run by Centre Hospitalier Universitaire de Nīmes at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 17 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Is stroke volume increased ≥ 15% as compared to baseline? (time frame: 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2018.