Ignite Creation Date:
2025-12-24 @ 12:36 PM
Ignite Modification Date:
2025-12-27 @ 4:10 PM
Study NCT ID:
NCT01089361
Status:
COMPLETED
Last Update Posted:
2017-08-21
First Post:
2010-03-12
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Immunomodulatory Properties of Ketamine in Sepsis
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D018805', 'term': 'Sepsis'}, {'id': 'D018746', 'term': 'Systemic Inflammatory Response Syndrome'}, {'id': 'D012772', 'term': 'Shock, Septic'}], 'ancestors': [{'id': 'D007239', 'term': 'Infections'}, {'id': 'D007249', 'term': 'Inflammation'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D012769', 'term': 'Shock'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D007649', 'term': 'Ketamine'}, {'id': 'D012965', 'term': 'Sodium Chloride'}], 'ancestors': [{'id': 'D003510', 'term': 'Cyclohexanes'}, {'id': 'D003516', 'term': 'Cycloparaffins'}, {'id': 'D006840', 'term': 'Hydrocarbons, Alicyclic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D002712', 'term': 'Chlorides'}, {'id': 'D006851', 'term': 'Hydrochloric Acid'}, {'id': 'D017606', 'term': 'Chlorine Compounds'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D017670', 'term': 'Sodium Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'dtalmor@bidmc.harvard.edu', 'phone': '617-754-2675', 'title': 'Dr. Daniel Talmor', 'organization': 'Beth Israel Deaconess Medical Center'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'Seven days from enrollment.', 'eventGroups': [{'id': 'EG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.', 'otherNumAtRisk': 9, 'otherNumAffected': 0, 'seriousNumAtRisk': 9, 'seriousNumAffected': 4}, {'id': 'EG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.', 'otherNumAtRisk': 10, 'otherNumAffected': 5, 'seriousNumAtRisk': 10, 'seriousNumAffected': 4}], 'otherEvents': [{'term': 'Tachycardia (atrial fibrillation)', 'notes': 'Clinically expected based on septic presentation. Treated with cardioversion and medication.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Delirium', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Salivation, excessive', 'notes': 'Possibly related', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}], 'seriousEvents': [{'term': 'Death', 'notes': "All deaths in this trial were expected based on patients' clinical course and followed withdrawal of clinical care. None were suspected of being related to trial participation.", 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 4, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE'}, {'term': 'Pericardial effusion', 'notes': 'Pericardial effusion, possible tamponade. Treated with drainage.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Ventricular tachycardia', 'notes': 'Treated with antiarrythmics', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Serum Levels of IL-6, IL-10 and TNFα', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'OG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}], 'classes': [{'title': 'Baseline IL-10', 'categories': [{'measurements': [{'value': '28', 'groupId': 'OG000', 'lowerLimit': '8.1', 'upperLimit': '246.9'}, {'value': '16', 'groupId': 'OG001', 'lowerLimit': '12.2', 'upperLimit': '19.6'}]}]}, {'title': 'Day 7 IL-10', 'categories': [{'measurements': [{'value': '9.3', 'groupId': 'OG000', 'lowerLimit': '4.7', 'upperLimit': '12.9'}, {'value': '6.3', 'groupId': 'OG001', 'lowerLimit': '5', 'upperLimit': '10.5'}]}]}, {'title': 'Baseline IL-6', 'categories': [{'measurements': [{'value': '3227.7', 'groupId': 'OG000', 'lowerLimit': '512', 'upperLimit': '7205.7'}, {'value': '613.8', 'groupId': 'OG001', 'lowerLimit': '320.8', 'upperLimit': '3190.5'}]}]}, {'title': 'Day 7 IL-6', 'categories': [{'measurements': [{'value': '322.8', 'groupId': 'OG000', 'lowerLimit': '96.8', 'upperLimit': '428'}, {'value': '266.2', 'groupId': 'OG001', 'lowerLimit': '56.3', 'upperLimit': '285.8'}]}]}, {'title': 'Baseline TNF-alpha', 'categories': [{'measurements': [{'value': '2.5', 'groupId': 'OG000', 'lowerLimit': '1.5', 'upperLimit': '6.2'}, {'value': '7.1', 'groupId': 'OG001', 'lowerLimit': '3.2', 'upperLimit': '7.9'}]}]}, {'title': 'Day 7 TNF-alpha', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000', 'lowerLimit': '1.2', 'upperLimit': '3.1'}, {'value': '6.3', 'groupId': 'OG001', 'lowerLimit': '2.4', 'upperLimit': '15.4'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'first 7 days of admission, Baseline and Day 7 reported', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Adverse Effects Attributable to Ketamine', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'OG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '7 days', 'unitOfMeasure': 'adverse events', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Organ Failures', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'OG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '7 days', 'description': 'Incidence of new organ failure as detected by Sequential Organ Failure Assessment \\[SOFA\\] score. Definitions are as follows. Central nervous system: delirium, coma, uncontrollable seizures, ICP\\>20cm H2O Cardiac: MAP \\<60mmHg, blood pressure supported with pressors, 50 \\> HR \\> 120 Respiratory: vented, RR\\>30, PaO2\\<60, PaCO2 \\> 55, Sat\\<92% Kidney: RIFLE criteria Anemia: Hct\\<27, transfusion of PRBC Thrombocytopenia: platelet \\< 50k, platelet transfusion Liver: biopsy, ALT\\>200, AST\\>200, t.bil\\>2.0, ALP\\>300 Coagulation failure: INR\\>2 if no anticoagulation therapy', 'unitOfMeasure': 'participants with increase in SOFA score', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Acute Physiology and Chronic Health Evaluation (APACHE) Scores', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'OG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}], 'classes': [{'categories': [{'measurements': [{'value': '25', 'spread': '8', 'groupId': 'OG000'}, {'value': '23', 'spread': '10', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'First 24 hours after ICU admission', 'description': 'Difference in average APACHE-II score between the intervention and placebo groups. APACHE II (Acute Physiology and Chronic Health Evaluation II) is a severity of disease classification system for patients admitted to the Intensive Care Unit. It uses an integer score from 0 to 71 that is computed based on age, 12 routine physiological measurements (i.e. heart rate, temperature, laboratory values), and previous health status obtained during the first 24 hours after ICU admission. Higher scores correspond to more severe disease and a higher risk of death.', 'unitOfMeasure': 'APACHE score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Length of Intensive Care Unit (ICU) Stay', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'OG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}], 'classes': [{'categories': [{'measurements': [{'value': '19', 'spread': '9', 'groupId': 'OG000'}, {'value': '20', 'spread': '9', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '28 days', 'unitOfMeasure': 'days', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': '28 Day Mortality', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'OG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}], 'classes': [{'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '28 days', 'unitOfMeasure': 'deaths', 'reportingStatus': 'POSTED'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'PCR Substudy', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Normal Saline Placebo', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.\n\nNormal Saline placebo: The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'OG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.\n\nKetamine: The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'timeFrame': 'Daily up to 7 days', 'description': 'PCR analysis on serum samples for presence of bacterial and mitochondrial DNA; This substudy was not done.', 'reportingStatus': 'POSTED', 'populationDescription': 'Not done'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'FG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Patients were recruited between 2009 and 2010 from the ICU.', 'preAssignmentDetails': 'All patients who consented were randomized to treatment or placebo.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Normal Saline', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'BG001', 'title': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '63', 'spread': '19', 'groupId': 'BG000'}, {'value': '60', 'spread': '11', 'groupId': 'BG001'}, {'value': '61', 'spread': '15', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 19}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-07', 'completionDateStruct': {'date': '2011-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-07-21', 'studyFirstSubmitDate': '2010-03-12', 'resultsFirstSubmitDate': '2015-12-22', 'studyFirstSubmitQcDate': '2010-03-17', 'lastUpdatePostDateStruct': {'date': '2017-08-21', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-07-21', 'studyFirstPostDateStruct': {'date': '2010-03-18', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-08-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2010-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'PCR Substudy', 'timeFrame': 'Daily up to 7 days', 'description': 'PCR analysis on serum samples for presence of bacterial and mitochondrial DNA; This substudy was not done.'}], 'primaryOutcomes': [{'measure': 'Serum Levels of IL-6, IL-10 and TNFα', 'timeFrame': 'first 7 days of admission, Baseline and Day 7 reported'}], 'secondaryOutcomes': [{'measure': 'Adverse Effects Attributable to Ketamine', 'timeFrame': '7 days'}, {'measure': 'Organ Failures', 'timeFrame': '7 days', 'description': 'Incidence of new organ failure as detected by Sequential Organ Failure Assessment \\[SOFA\\] score. Definitions are as follows. Central nervous system: delirium, coma, uncontrollable seizures, ICP\\>20cm H2O Cardiac: MAP \\<60mmHg, blood pressure supported with pressors, 50 \\> HR \\> 120 Respiratory: vented, RR\\>30, PaO2\\<60, PaCO2 \\> 55, Sat\\<92% Kidney: RIFLE criteria Anemia: Hct\\<27, transfusion of PRBC Thrombocytopenia: platelet \\< 50k, platelet transfusion Liver: biopsy, ALT\\>200, AST\\>200, t.bil\\>2.0, ALP\\>300 Coagulation failure: INR\\>2 if no anticoagulation therapy'}, {'measure': 'Acute Physiology and Chronic Health Evaluation (APACHE) Scores', 'timeFrame': 'First 24 hours after ICU admission', 'description': 'Difference in average APACHE-II score between the intervention and placebo groups. APACHE II (Acute Physiology and Chronic Health Evaluation II) is a severity of disease classification system for patients admitted to the Intensive Care Unit. It uses an integer score from 0 to 71 that is computed based on age, 12 routine physiological measurements (i.e. heart rate, temperature, laboratory values), and previous health status obtained during the first 24 hours after ICU admission. Higher scores correspond to more severe disease and a higher risk of death.'}, {'measure': 'Length of Intensive Care Unit (ICU) Stay', 'timeFrame': '28 days'}, {'measure': '28 Day Mortality', 'timeFrame': '28 days'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['systemic inflammatory syndrome', 'sepsis syndrome', 'septic shock', 'Cytokine', 'Ketamine'], 'conditions': ['Sepsis']}, 'referencesModule': {'references': [{'pmid': '12520644', 'type': 'BACKGROUND', 'citation': 'Calandra T, Bochud PY, Heumann D. Cytokines in septic shock. Curr Clin Top Infect Dis. 2002;22:1-23. No abstract available.'}, {'pmid': '17032758', 'type': 'BACKGROUND', 'citation': 'Laudanski K, Miller-Graziano C, Xiao W, Mindrinos MN, Richards DR, De A, Moldawer LL, Maier RV, Bankey P, Baker HV, Brownstein BH, Cobb JP, Calvano SE, Davis RW, Tompkins RG. Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways. Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15564-9. doi: 10.1073/pnas.0607028103. Epub 2006 Oct 10.'}, {'pmid': '10475301', 'type': 'BACKGROUND', 'citation': 'Kawasaki T, Ogata M, Kawasaki C, Ogata J, Inoue Y, Shigematsu A. Ketamine suppresses proinflammatory cytokine production in human whole blood in vitro. Anesth Analg. 1999 Sep;89(3):665-9. doi: 10.1097/00000539-199909000-00024.'}]}, 'descriptionModule': {'briefSummary': 'The aim of the study is to assess the effect of short-term infusion of ketamine at analgesic dosage on the immune response, morbidity and mortality among patients suffering from septic shock. We hypothesize that ketamine will modulate the cytokine response to sepsis and reduce morbidity and mortality.', 'detailedDescription': '1. Basic design A randomized placebo controlled trial of low dose ketamine in patients with severe sepsis in the ICU.\n2. Assembly of Subjects Patients meeting the ACCP/ SCCM definition of severe sepsis will be enrolled in the study5. These patients should have a known or suspected source of infection based on the clinical data at the time of screening. They must exhibit 3 or more of the following signs of clinical inflammation\n\n * Core temperature \\< 36ºC or \\> 38ºC.\n * Heart rate of 90 or greater not explained by another medical condition.\n * A respiratory rate of \\> 20 min-1, a PaCO2 \\< 32min-1 or the need for mechanical ventilation.\n * A white cell count of \\< 4000 cell/ml or \\> 12000 cells/ml or a WBC showing greater then 10% immature neutrophils.\n\n In addition the patient will have to be within 12 hours of the development of one or more organ dysfunctions as outlined in Bone et al 5.\n\n Several exclusion criteria will be in place to safeguard patient\'s safety 11. Patients with closed head trauma or with increased intracranial pressure will be excluded. Patients with a history of psychotic mental disease will also be excluded as they may be at risk for relapse following administration of ketamine.\n3. Exposures Patients will be randomized into a treatment group and a control group. The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours. To help insure protocol compliance and safeguard patient care, a member of the study team will be present at the time the study drug infusion is started, and will also contact the clinical team when the infusion is due to be terminated. The dose of the ketamine is considered analgesic not anesthetic in nature and follows general practice in pain management 11. The control group will receive a similar volume of normal saline as a placebo. Additionally all patients enrolled in the study will receive lorazepam 1mg every 6 hours to further lower the risk of side effect from ketamine. Patients, staff and investigators will all be blinded to the treatment groups. All other care, including the need for further sedation, will be according to unit protocols.\n\n Prior to administration of the study drug a 10cc sample of the patient\'s blood will be drawn and frozen for later analysis. 2 hours after starting infusion another 10ml of blood will be obtained. Following 24 hour infusion of ketamine, blood samples will be drawn each day, for the following 7 days, processed and frozen.\n\n Patient demographic and clinical data will be collected on admission to the study and daily follow-up. Particular attention will be paid to calculation of the patient\'s APACHE II/MODS score on the day of admission and on the following days22. This will allow us to compare severity of disease in a potentially heterogeneous ICU patient population. We will also monitor use of the vasopressors, additional pain and sedative medication and physiological parameters (BP, HR, Sat, ABG, LFT, lactic acid) in studied population before and after administration of the drug. The adverse effect of ketamine will assessed by using delirium questionnaire and special chart designed to capture the emergence of side effect (delirium, psychosis, others).\n4. Outcomes and their measurement The primary outcome of the study will be serum levels of IL-6, IL-10 and TNFα and other cytokines over the first 7 days of admission. Measurement of cytokine levels will be done using enzyme linked immunoassay, or with flow cytometry at the end of the study by at researcher who will be blinded to the study groups. We also plan to separate leukocytes for further studies of mRNA levels to corroborate serum cytokine levels with activity of mRNA.\n\n Secondary outcomes will include adverse effects attributable to ketamine, organ failures, daily APACHE scores, length of ICU stay and 28 day mortality. A clinical research associate will carry out a daily patient assessment. This investigator will be blinded to the treatment groups. Data will be collected on a patient study chart. In addition to the incidence of organ dysfunction, death and length of stay, specific information will be gathered to assess patient\'s level of conscience, possible dreams or hallucinations and other effects, which may be attributable to ketamine.\n5. Substudy of serum samples We plan to perform real-time quantitative PCR analyses on the existing serum samples for the presence of bacterial and mitochondrial DNA on the samples. We will use primers targeting bacterial 16S-rRNA consensus areas and primers targeting gram-positive (S. Aureus), gram-negative (e. coli) and anaerobic (B. Fragilis) species. These tests may be able to accurately discriminate between systemic inflammation ("SIRS") due to invasive bacterial infections from SIRS due to tissue injury than do conventional bacteriologic analyses.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '100 Years', 'minimumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patients meeting the ACCP/ SCCM definition of severe sepsis will be enrolled in the study. These patients should have a known or suspected source of infection.\n* Patients within 12 hours of the development of one or more organ dysfunctions\n* Patients must exhibit 3 or more of the following signs of clinical inflammation:\n\n * Core temperature \\< 36ºC or \\> 38ºC.\n * Heart rate of 90 or greater not explained by another medical condition.\n * A respiratory rate of \\> 20 min-1, a PaCO2 \\< 32min-1 or the need for mechanical ventilation.\n * A white blood cell count of \\< 4000 cell/ml or \\> 12000 cells/ml or a WBC showing greater then 10% immature neutrophils.\n\nExclusion Criteria:\n\n* pregnant\n* increased intracranial pressure or closed head injury\n* history of psychotic mental disease\n* receiving Continuous Veno - Venous Hemofiltration'}, 'identificationModule': {'nctId': 'NCT01089361', 'briefTitle': 'Immunomodulatory Properties of Ketamine in Sepsis', 'organization': {'class': 'OTHER', 'fullName': 'Beth Israel Deaconess Medical Center'}, 'officialTitle': 'Immunomodulatory Properties of Ketamine in Sepsis', 'orgStudyIdInfo': {'id': '2009P000259'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Normal saline placebo', 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.', 'interventionNames': ['Drug: Normal Saline placebo']}, {'type': 'EXPERIMENTAL', 'label': 'Ketamine', 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.', 'interventionNames': ['Drug: Ketamine']}], 'interventions': [{'name': 'Ketamine', 'type': 'DRUG', 'otherNames': ['Ketamine Hydrochloride', 'Ketalar'], 'description': 'The treatment group will receive 0.25mg/kg of ketamine over a period of one hour followed by a continuous infusion of ketamine at 0.1 mg/kg/hr for a further 23 hours.', 'armGroupLabels': ['Ketamine']}, {'name': 'Normal Saline placebo', 'type': 'DRUG', 'otherNames': ['0.9% Sodium Chloride Solution'], 'description': 'The control group will receive 0.25mg/kg of normal saline over a period of one hour followed by a continuous infusion of normal saline at 0.1 mg/kg/hr for a further 23 hours.', 'armGroupLabels': ['Normal saline placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '02215', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Beth Israel Deaconess Medical Center', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}], 'overallOfficials': [{'name': 'Daniel Talmor, MD, MPH', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Beth Israel Deaconess Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Beth Israel Deaconess Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor of Anaesthesia', 'investigatorFullName': 'Daniel Talmor', 'investigatorAffiliation': 'Beth Israel Deaconess Medical Center'}}}}