Septic ShockPhase 2THANENCT02120404
Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock
A Phase 2 study testing Esmolol administration in people with Septic Shock, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Esmolol administration
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2015to Oct 2023
- Phase
- Phase 2
- 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
- Patient aged ≥ 18 years;
- Patient with septic shock;
- Patient with arterial catheter, central venous catheter with PVC and PiCCO;
- Consent signed by patient. In the absence of a consent signed by patient himself, a consent by a family member will be sought. As soon as possible, the patient will be informed and asked to sign a consent for continuing of study;
- Hemodynamic stability of patient during 1 hour without change in norepinephrine dosage;
- Treatment with noradrenaline for less than 48 hours.
Who cannot join
- Need of noradrenaline > 3 mg/h;
- Treatment with dobutamine;
- Personal history of severe asthma;
- Personal history of severe chronic obstructive pulmonary disease;
- Personal history of pulmonary hypertension;
- Personal history of second degree or third degree atrioventricular block without pacemaker;
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- Personal history of sinoatrial block without pacemaker;
- Chronic heart failure with ejection fraction < 40%;
- Severe atrioventricular nodal bradycardia (heart rate < 70 bpm);
- Mean arterial pressure < 65 mm Hg;
- Hypersensitivity to esmolol;
- Prinzmetal angina;
- Pheochromocytoma without treatment;
- Pregnancy woman;
- Breastfeeding woman;
- Peripheral arterial disease;
- Patient with pacemaker;
- Chronic treatment with a beta blocker;
- Concomitant treatment with bepridil, diltiazem, verapamil, amiodarone, propafenone, Class Ia antiarrythmics (hydroquinidine, disopyramide) or baclofen;
- Patient < 18 years;
- Patient under the care of a guardian;
- Therapeutic futility;
- Lack of medical insurance.
Trial locations and contacts
1 site in 1 country.
About this study
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%.
Read the detailed description
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 study:
- The expression of adrenergic receptors and their genetic polymorphisms on circulating immune cells.
- The Th1/Th2 balance in immune cells.
Each patient will be followed-up for 28 days.
The variation of MAP and of cardiac output induced by esmolol should not exceed 15% of baseline values. If the variation is more important esmolol administration will be stopped and the hemodynamical tolerance will be defined as poor.
- Conditions
- Septic Shock
- Being tested
- Esmolol administration
- Keywords
- septic shock, hemodynamic tolerance, esmolol
- Medical subject headings
- Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esmolol administrationDrug
Also called BREVIBLOC 10 mg/ml
Esmolol will be administered during 24 hours, beginning with a titration period to determine the minimal dose allowing to achieve the randomized heart rate reduction of 10% or 20%, as defined by randomization.
Titration will be performed in sequences of increasing doses, beginning with 5 μg/kg/min as initial dose, and increasing by 5 μg/kg/min each 30 minutes until the target heart rate reduction is obtained. The maximum dose is 200 μg/kg/min.
The titrated dose will be maintained for a total duration of 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Control group (GC) | No intervention | Control group: no esmolol administration |
| Group 10 (G10) | Experimental | Esmolol titrated in order to reduce heart rate by 10% as compared to baseline heart rate Receives: Drug: Esmolol administration |
| Group 20 (G20) | Experimental | Esmolol titrated in order to reduce heart rate by 20% as compared to baseline heart rate Receives: Drug: Esmolol administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of hemodynamic parameters between 3 groups
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).
Measured: 24 hours
Immunomodulatory effect
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.
Measured: 24 hours
Secondary outcomes (4)
Comparison of number and severity of organ failures, between the 3 groups
3 groups will be evaluated by SOFA score.
Measured: 28 days
Comparison of autonomic nervous system activity between the 3 groups
Power spectrum analysis of heart rate variability.
Measured: 24 hours
Comparison of mortality in the 3 groups
Measured: 28 days
Comparison in the 3 groups of the correlations between the biomarkers and the hemodynamic data
The biomarkers in plasma levels: cortisol, catecholamine, proinflammatory cytokines and anti-inflammatory cytokines.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2014 (estimated)
- Study startApr 2015
- Primary completionOct 2023 (estimated)
- Study completionOct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Baxter Healthcare Corporation
- Responsible party
- Sponsor
- Investigators
- Djillali ANNANE, MD, PhD, Principal investigator, ICU, Hôpital Raymond Poincaré, 92380 Garches, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02120404
- Sponsor's protocol ID
- P120912
- Other IDs
- 2013-005174-22
- Acronym
- THANE
- Status last verified
- Aug 2023
- First submitted
- 18 Apr 2014
- Last updated
- 31 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock
- ClinicalTrials.gov ID
- NCT02120404
- Acronym / sponsor ID
- THANE / P120912
- Conditions
- Septic Shock
- Keywords
- septic shock, hemodynamic tolerance, esmolol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Baxter Healthcare Corporation
- Study start
- Apr 2015 (actual)
- Primary completion
- Oct 2023 (estimated)
- Study completion
- Oct 2023 (estimated)
- First posted
- 22 Apr 2014 (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 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 description
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 study:
- The expression of adrenergic receptors and their genetic polymorphisms on circulating immune cells.
- The Th1/Th2 balance in immune cells.
Each patient will be followed-up for 28 days.
The variation of MAP and of cardiac output induced by esmolol should not exceed 15% of baseline values. If the variation is more important esmolol administration will be stopped and the hemodynamical tolerance will be defined as poor.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control group (GC) | No intervention | –Control group: no esmolol administration |
| Group 10 (G10) | Experimental | Drug: Esmolol administrationEsmolol titrated in order to reduce heart rate by 10% as compared to baseline heart rate |
| Group 20 (G20) | Experimental | Drug: Esmolol administrationEsmolol titrated in order to reduce heart rate by 20% as compared to baseline heart rate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patient aged ≥ 18 years;
- Patient with septic shock;
- Patient with arterial catheter, central venous catheter with PVC and PiCCO;
- Consent signed by patient. In the absence of a consent signed by patient himself, a consent by a family member will be sought. As soon as possible, the patient will be informed and asked to sign a consent for continuing of study;
- Hemodynamic stability of patient during 1 hour without change in norepinephrine dosage;
Key exclusion criteria (23 listed)
- Need of noradrenaline > 3 mg/h;
- Treatment with dobutamine;
- Personal history of severe asthma;
- Personal history of severe chronic obstructive pulmonary disease;
- Personal history of pulmonary hypertension;
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 |
|---|---|---|
| Esmolol administrationAlso: BREVIBLOC 10 mg/mlEsmolol will be administered during 24 hours, beginning with a titration period to determine the minimal dose allowing to achieve the randomized heart rate reduction of 10% or 20%, as defined by randomization. Titration will be performed in sequences of increasing doses, beginning with 5 μg/kg/min as initial dose, and increasing by 5 μg/kg/min each 30 minutes until the target heart rate reduction is obtained. The maximum dose is 200 μg/kg/min. The titrated dose will be maintained for a total duration of 24 hours. | Drug | Group 10 (G10), Group 20 (G20) |
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.
4 secondary outcomes
Comparison of number and severity of organ failures, between the 3 groups
Time frame: 28 days
Comparison of autonomic nervous system activity between the 3 groups
Time frame: 24 hours
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2023.
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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.
Djillali ANNANE, MD, PhD principal investigator
ICU, Hôpital Raymond Poincaré, 92380 Garches, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Esmolol administration in people with Septic Shock, run by Assistance Publique - Hôpitaux de Paris at 1 site 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 6 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Comparison of hemodynamic parameters between 3 groups (time frame: 24 hours). The study lists 2 primary outcomes in all. 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 31 Aug 2023.