Ignite Creation Date:
2025-12-24 @ 5:05 PM
Ignite Modification Date:
2026-01-01 @ 12:58 PM
Study NCT ID:
NCT01031550
Status:
TERMINATED
Last Update Posted:
2017-03-20
First Post:
2009-12-10
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Isoflurane Preconditioning for Liver Resections
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008107', 'term': 'Liver Diseases'}], 'ancestors': [{'id': 'D004066', 'term': 'Digestive System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D007530', 'term': 'Isoflurane'}, {'id': 'D015742', 'term': 'Propofol'}], 'ancestors': [{'id': 'D008738', 'term': 'Methyl Ethers'}, {'id': 'D004987', 'term': 'Ethers'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D010636', 'term': 'Phenols'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'yuriygubenko@yahoo.com', 'phone': '973 972-5007', 'title': 'Yuriy Gubenko, MD', 'organization': 'UMDNJ'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Due to termination of the study no data analysis was performed.'}}, 'adverseEventsModule': {'timeFrame': 'Day of surgery and 7 days later', 'eventGroups': [{'id': 'EG000', 'title': 'Standard Anesthetic Management', 'description': 'standard anesthetic management with propofol 100-150mcg/kg/min', 'otherNumAtRisk': 5, 'otherNumAffected': 0, 'seriousNumAtRisk': 5, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Preconditioning With 2 MAC Isoflurane Group', 'description': 'preconditioning with isoflurane , anesthesia will be maintained with 1MAC of Isoflurane according to age and end-expiratory concentration. Thirty minutes before the anticipated inflow occlusion and commencement of liver transaction, Isoflurane concentration will be gradually increased to 2 MAC over a period of 5 minutes (induction) and maintained at 2 MAC for 10 minutes (preconditioning). Then the concentration of Isoflurane will be decreased to 1 MAC during next 15 minutes (washout).', 'otherNumAtRisk': 3, 'otherNumAffected': 0, 'seriousNumAtRisk': 3, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': "Post Operative Complications Grade IIIb or Greater According to Clavien's Classification Which is a Classification System Used to Grade Surgical Complications", 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Standard Anesthetic Management', 'description': 'standard anesthetic management with propofol 100-150mcg/kg/min'}, {'id': 'OG001', 'title': 'Preconditioning With 2 MAC Isoflurane Group', 'description': 'preconditioning with isoflurane , anesthesia will be maintained with 1MAC of Isoflurane according to age and end-expiratory concentration. Thirty minutes before the anticipated inflow occlusion and commencement of liver transaction, Isoflurane concentration will be gradually increased to 2 MAC over a period of 5 minutes (induction) and maintained at 2 MAC for 10 minutes (preconditioning). Then the concentration of Isoflurane will be decreased to 1 MAC during next 15 minutes (washout).'}], 'timeFrame': 'first 7 post operative days', 'description': "Post operative complications grade IIIB or greater according to Clavien's classification: IIIb=complication necessitating an intervention under general anesthesia; Grade IV=Life threatening complications requiring ICU management, IV a =single organ dysfunction, IVb=multi-organ dysfunction; V=death Suffix d(disability)=subject suffers from complication at time of discharge. This label indicates the need for a follow up to fully evaluate the complication.", 'reportingStatus': 'POSTED', 'populationDescription': 'Due to termination of the study no data analysis was performed.'}, {'type': 'SECONDARY', 'title': 'Peak Postoperative AST, ALT and T Bili', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Standard Anesthetic Management', 'description': 'standard anesthetic management'}, {'id': 'OG001', 'title': 'Preconditioning With 2 MAC Isoflurane Group', 'description': 'preconditioning with isoflurane'}], 'timeFrame': 'first 7 post operative days', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to termination of the study no data analysis was performed.'}, {'type': 'SECONDARY', 'title': 'Length of ICU and Hospital Stay', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Standard Anesthetic Management', 'description': 'standard anesthetic management'}, {'id': 'OG001', 'title': 'Preconditioning With 2 MAC Isoflurane Group', 'description': 'preconditioning with isoflurane'}], 'timeFrame': 'first 7 post operative days', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to termination of the study no data analysis was performed.'}, {'type': 'SECONDARY', 'title': 'Decrease in Liver Lipid Peroxidation and Apoptosis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Standard Anesthetic Management', 'description': 'standard anesthetic management'}, {'id': 'OG001', 'title': 'Preconditioning With 2 MAC Isoflurane Group', 'description': 'preconditioning with isoflurane'}], 'timeFrame': 'first 7 post operative days', 'reportingStatus': 'POSTED', 'populationDescription': 'Due to termination of the study no data analysis was performed.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Standard Anesthetic Management', 'description': 'standard anesthetic management propofol 100-150mcg/kg/min'}, {'id': 'FG001', 'title': 'Preconditioning With 2 MAC Isoflurane Group', 'description': 'preconditioning with isoflurane, anesthesia will be maintained with 1MAC of Isoflurane according to age and end-expiratory concentration. Thirty minutes before the anticipated inflow occlusion and commencement of liver transaction, Isoflurane concentration will be gradually increased to 2 MAC over a period of 5 minutes (induction) and maintained at 2 MAC for 10 minutes (preconditioning). Then the concentration of Isoflurane will be decreased to 1 MAC during next 15 minutes (washout).'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Subjects will be randomized in two strata, those with and without preexisting liver disease. Subjects will be screened in pre admission testing', 'preAssignmentDetails': 'Subjects may withdraw consent'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Standard Anesthetic Management', 'description': 'standard anesthetic management with propofol 100-150mcg/kg/min'}, {'id': 'BG001', 'title': 'Preconditioning With 2 MAC Isoflurane Group', 'description': 'preconditioning with isoflurane anesthesia will be maintained with 1MAC of Isoflurane according to age and end-expiratory concentration. Thirty minutes before the anticipated inflow occlusion and commencement of liver transaction, Isoflurane concentration will be gradually increased to 2 MAC over a period of 5 minutes (induction) and maintained at 2 MAC for 10 minutes (preconditioning). Then the concentration of Isoflurane will be decreased to 1 MAC during next 15 minutes (washout).'}, {'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': '4', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '40', 'spread': '10', 'groupId': 'BG000'}, {'value': '38', 'spread': '8', 'groupId': 'BG001'}, {'value': '39', 'spread': '9', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 8}}, 'statusModule': {'whyStopped': 'We no longer had an appropriate patient population.Study closed', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2010-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-02', 'completionDateStruct': {'date': '2012-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-02-13', 'studyFirstSubmitDate': '2009-12-10', 'resultsFirstSubmitDate': '2013-09-16', 'studyFirstSubmitQcDate': '2009-12-11', 'lastUpdatePostDateStruct': {'date': '2017-03-20', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2013-12-11', 'studyFirstPostDateStruct': {'date': '2009-12-14', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-12-12', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2012-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': "Post Operative Complications Grade IIIb or Greater According to Clavien's Classification Which is a Classification System Used to Grade Surgical Complications", 'timeFrame': 'first 7 post operative days', 'description': "Post operative complications grade IIIB or greater according to Clavien's classification: IIIb=complication necessitating an intervention under general anesthesia; Grade IV=Life threatening complications requiring ICU management, IV a =single organ dysfunction, IVb=multi-organ dysfunction; V=death Suffix d(disability)=subject suffers from complication at time of discharge. This label indicates the need for a follow up to fully evaluate the complication."}], 'secondaryOutcomes': [{'measure': 'Peak Postoperative AST, ALT and T Bili', 'timeFrame': 'first 7 post operative days'}, {'measure': 'Length of ICU and Hospital Stay', 'timeFrame': 'first 7 post operative days'}, {'measure': 'Decrease in Liver Lipid Peroxidation and Apoptosis', 'timeFrame': 'first 7 post operative days'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['liver resection for liver disease'], 'conditions': ['Liver Disease']}, 'descriptionModule': {'briefSummary': 'The objective is to examine the efficacy of isoflurane (inhaled anesthetic gas) to induce clinically effective preconditioning in patients undergoing elective hepatic surgery.', 'detailedDescription': "Elective liver resection is performed primarily for the treatment of benign and malignant liver tumors1. In addition, with the increasing use of living donor liver transplantation to supplement the inadequate pool of cadaveric organs available, liver resection is performed also in live liver donors2.\n\nPostoperative complications are common following liver resections. Occurrence of complications increases ICU and hospital stay, and resource utilization. The most serious postoperative complication after a liver resection is post-resectional liver failure (PLF)3. Risk factors for the development of PLF are preexisting liver disease, especially cirrhosis, excessive blood loss during liver resection, and liver ischemia and reperfusion injury4-5. Several strategies have been developed to combat excessive intra-operative blood loss including: lowering the central venous pressure6, hypoventilation7, and hepatic inflow occlusion using an atraumatic clamp8 (Pringle's maneuver)9; While inflow occlusion is the most important of these steps, hepatic ischemia and reperfusion is an important sequel to the inflow occlusion. Therefore, interventions which decrease hepatic ischemia reperfusion injury to the liver have the potential to improve outcomes following liver resection.\n\nA strategy that directly modulates the hepatic response to ischemia is ischemic preconditioning (IPC). Classically, IPC has been induced by exposing an organ to brief periods of ischemia and reperfusion before exposing the organ to a more prolonged ischemic insult. In patients undergoing liver resection, IPC decreases postoperative aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels15. IPC is also associated with decreased histological evidence of apoptosis as well as immunohistochemical evidence of increased protective gene expression16 in the liver.\n\nThe primary disadvantage of IPC is the direct stress to the target organ as well as the mechanical trauma to major vasculature.\n\nMore recently, it has been found that inhaled volatile anesthetics such as Desflurane, Sevoflurane and Isoflurane induce similar preconditioning effects19 without causing any significant direct organ damage. While several animal studies exist, which demonstrate the hepatoprotective effect of volatile anesthetics on the liver23, there is only limited clinical data examining their effect in humans. One recent small clinical study, examining the preconditioning effect of volatile anesthetic on patients undergoing liver surgery, showed that anesthetic pre conditioning (APC) using Sevoflurane significantly decreased the several measures of liver dysfunction postoperatively24.\n\nHowever, Sevoflurane is partially metabolized by the liver and may increase plasma fluoride concentration. Also, it may react with CO2 absorbent and can produce Compound-A, which in turn has been linked to nephrotoxicity. On the other hand, isoflurane, another inhalational anesthetic agent commonly used during liver surgery also has been shown to have a preconditioning effect in experimental animals, and does not carry the potential side effects of sevoflurane.\n\nTherefore, the primary objective of this study is to examine the efficacy of isoflurane to induce clinically effective preconditioning in patients undergoing elective hepatic surgery.\n\nStudy Design:\n\nIn this prospective study, patients undergoing elective liver resection with inflow occlusion (Pringle maneuver) at UH, Newark will be randomized (1:1) to either standard anesthetic management with Propofol (No APC group) or anesthetic preconditioning with 2 minimum alveolar concentration (MAC) of isoflurane (APC group). Because preexisting liver disease, especially cirrhosis, is an important determinant of post operative outcomes, and to balance the randomization of subjects regarding this important variable randomization will be stratified into those with and without preexisting liver disease. The primary endpoint is the occurrence of postoperative complications grade IIIb or greater (Clavien's classification). The secondary endpoints are peak postoperative aspartate and alanine aminotransferase (AST and ALT) and total bilirubin (T Bili), length of ICU and hospital stay, and a decrease in liver lipid peroxidation and apoptosis"}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* patients with liver tumors undergoing liver resection of \\> 1 segment liver resection must be performed with inflow occlusion \\> 30 min\n\nExclusion Criteria:\n\n* patients undergoing liver resection of one segment or less\n* patients undergoing laparoscopic liver resection\n* patients in whom the liver resection is performed with no inflow occlusion or inflow occlusion of \\< 30 min'}, 'identificationModule': {'nctId': 'NCT01031550', 'briefTitle': 'Isoflurane Preconditioning for Liver Resections', 'organization': {'class': 'OTHER', 'fullName': 'Rutgers, The State University of New Jersey'}, 'officialTitle': 'Isoflurane Induced Anesthetic Preconditioning in Elective Liver Resection', 'orgStudyIdInfo': {'id': '0120090226'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'standard anesthetic management', 'description': 'standard anesthetic management with propofol 100-150mcg/kg/min', 'interventionNames': ['Drug: propofol']}, {'type': 'EXPERIMENTAL', 'label': 'preconditioning with 2 MAC isoflurane group', 'description': 'After induction, anesthesia will be maintained with 1MAC (minimum alveolar concentration) of Isoflurane according to age and end-expiratory concentration. Thirty minutes before the anticipated inflow occlusion and commencement of liver transaction, Isoflurane concentration will be gradually increased to 2 MAC over a period of 5 minutes (induction) and maintained at 2 MAC for 10 minutes (preconditioning). Then the concentration of Isoflurane will be decreased to 1 MAC during next 15 minutes (washout).', 'interventionNames': ['Drug: isoflurane']}], 'interventions': [{'name': 'isoflurane', 'type': 'DRUG', 'description': 'isoflurane an anesthetic gas agent administered at specific times at a flow of 2 MAC', 'armGroupLabels': ['preconditioning with 2 MAC isoflurane group']}, {'name': 'propofol', 'type': 'DRUG', 'otherNames': ['diprivan'], 'description': 'standard of care', 'armGroupLabels': ['standard anesthetic management']}]}, 'contactsLocationsModule': {'locations': [{'zip': '07101', 'city': 'Newark', 'state': 'New Jersey', 'country': 'United States', 'facility': 'UMDNJ-University Hospital', 'geoPoint': {'lat': 40.73566, 'lon': -74.17237}}], 'overallOfficials': [{'name': 'Yuriy Gubenko, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Rutgers, The State University of New Jersey'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Rutgers, The State University of New Jersey', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Investigator Intiated Dept of Anesthesia', 'investigatorFullName': 'Yuriy Gubenko, MD', 'investigatorAffiliation': 'Rutgers, The State University of New Jersey'}}}}