Ignite Creation Date:
2025-12-24 @ 9:07 PM
Ignite Modification Date:
2026-04-04 @ 12:21 AM
Study NCT ID:
NCT02120404
Status:
UNKNOWN
Last Update Posted:
2023-08-31
First Post:
2014-04-18
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012772', 'term': 'Shock, Septic'}], 'ancestors': [{'id': 'D018805', 'term': 'Sepsis'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012769', 'term': 'Shock'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C036604', 'term': 'esmolol'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 45}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2015-04', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-08', 'completionDateStruct': {'date': '2023-10', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-08-30', 'studyFirstSubmitDate': '2014-04-18', 'studyFirstSubmitQcDate': '2014-04-18', 'lastUpdatePostDateStruct': {'date': '2023-08-31', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-04-22', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2023-10', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Comparison of hemodynamic parameters between 3 groups', 'timeFrame': '24 hours', 'description': '3 groups: GC, G10 and G20.\n\nThe 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).'}, {'measure': 'Immunomodulatory effect', 'timeFrame': '24 hours', 'description': 'Immunomodulatory effect of esmolol will be evaluated notably by the ratio of IL6 / IL10.\n\nThe decrease of this ratio in comparison with the value at baseline (H0) will be considered as an indicator of esmolol efficacy as immunomodulator.'}], 'secondaryOutcomes': [{'measure': 'Comparison of number and severity of organ failures, between the 3 groups', 'timeFrame': '28 days', 'description': '3 groups will be evaluated by SOFA score.'}, {'measure': 'Comparison of autonomic nervous system activity between the 3 groups', 'timeFrame': '24 hours', 'description': 'Power spectrum analysis of heart rate variability.'}, {'measure': 'Comparison of mortality in the 3 groups', 'timeFrame': '28 days'}, {'measure': 'Comparison in the 3 groups of the correlations between the biomarkers and the hemodynamic data', 'timeFrame': '24 hours', 'description': 'The biomarkers in plasma levels: cortisol, catecholamine, proinflammatory cytokines and anti-inflammatory cytokines.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['septic shock, hemodynamic tolerance, esmolol'], 'conditions': ['Septic Shock']}, 'descriptionModule': {'briefSummary': 'The purpose of this study is :\n\n\\- to evaluate the hemodynamic tolerance of esmolol titrated to obtain a lowering of heart rate of 10% or 20%.', 'detailedDescription': '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.\n\nThe study will enroll adult patients hospitalized in ICU, for severe septic shock requiring treatment by a vasopressor.\n\nA 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.\n\nThis multicenter study will be performed in 3 investigation sites.\n\nThe following parameters will be evaluated at different moments during the 28 days follow up of each patient, mainly:\n\n* Origin of sepsis, SOFA score.\n* Hemodynamic parameters will be continuously recorded for the 24 hours of experimental period.\n* Cardiovascular variability (arterial pressure and heart rate) will be recorded for 24 hours.\n* 3 echocardiograms at H0, H12 and H24 will be performed.\n* 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:\n\n * The expression of adrenergic receptors and their genetic polymorphisms on circulating immune cells.\n * The Th1/Th2 balance in immune cells.\n\nEach patient will be followed-up for 28 days.\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patient aged ≥ 18 years;\n* Patient with septic shock;\n* Patient with arterial catheter, central venous catheter with PVC and PiCCO;\n* 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;\n* Hemodynamic stability of patient during 1 hour without change in norepinephrine dosage;\n* Treatment with noradrenaline for less than 48 hours.\n\nExclusion Criteria:\n\n* Need of noradrenaline \\> 3 mg/h;\n* Treatment with dobutamine;\n* Personal history of severe asthma;\n* Personal history of severe chronic obstructive pulmonary disease;\n* Personal history of pulmonary hypertension;\n* Personal history of second degree or third degree atrioventricular block without pacemaker;\n* Personal history of sinoatrial block without pacemaker;\n* Chronic heart failure with ejection fraction \\< 40%;\n* Severe atrioventricular nodal bradycardia (heart rate \\< 70 bpm);\n* Mean arterial pressure \\< 65 mm Hg;\n* Hypersensitivity to esmolol;\n* Prinzmetal angina;\n* Pheochromocytoma without treatment;\n* Pregnancy woman;\n* Breastfeeding woman;\n* Peripheral arterial disease;\n* Patient with pacemaker;\n* Chronic treatment with a beta blocker;\n* Concomitant treatment with bepridil, diltiazem, verapamil, amiodarone, propafenone, Class Ia antiarrythmics (hydroquinidine, disopyramide) or baclofen;\n* Patient \\< 18 years;\n* Patient under the care of a guardian;\n* Therapeutic futility;\n* Lack of medical insurance.'}, 'identificationModule': {'nctId': 'NCT02120404', 'acronym': 'THANE', 'briefTitle': 'Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Pilot Phase II Study: Hemodynamic Tolerance and Anti-inflammatory Effects of Esmolol During the Treatment of Septic Shock', 'orgStudyIdInfo': {'id': 'P120912'}, 'secondaryIdInfos': [{'id': '2013-005174-22', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'NO_INTERVENTION', 'label': 'Control group (GC)', 'description': 'Control group: no esmolol administration'}, {'type': 'EXPERIMENTAL', 'label': 'Group 10 (G10)', 'description': 'Esmolol titrated in order to reduce heart rate by 10% as compared to baseline heart rate', 'interventionNames': ['Drug: Esmolol administration']}, {'type': 'EXPERIMENTAL', 'label': 'Group 20 (G20)', 'description': 'Esmolol titrated in order to reduce heart rate by 20% as compared to baseline heart rate', 'interventionNames': ['Drug: Esmolol administration']}], 'interventions': [{'name': 'Esmolol administration', 'type': 'DRUG', 'otherNames': ['BREVIBLOC 10 mg/ml'], 'description': '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.\n\nTitration 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.\n\nThe titrated dose will be maintained for a total duration of 24 hours.', 'armGroupLabels': ['Group 10 (G10)', 'Group 20 (G20)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '92380', 'city': 'Garches', 'state': 'Haute Des Seine', 'country': 'France', 'facility': 'ICU, Hôpital Raymond Poincaré', 'geoPoint': {'lat': 48.84226, 'lon': 2.18232}}], 'overallOfficials': [{'name': 'Djillali ANNANE, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'ICU, Hôpital Raymond Poincaré, 92380 Garches, France'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'collaborators': [{'name': 'Baxter Healthcare Corporation', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}