Ignite Creation Date:
2025-12-24 @ 7:48 PM
Ignite Modification Date:
2025-12-29 @ 5:31 AM
Study NCT ID:
NCT00359203
Status:
COMPLETED
Last Update Posted:
2025-07-18
First Post:
2006-07-31
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
ISSUE3: International Study on Syncope of Uncertain Etiology 3
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D013575', 'term': 'Syncope'}], 'ancestors': [{'id': 'D014474', 'term': 'Unconsciousness'}, {'id': 'D003244', 'term': 'Consciousness Disorders'}, {'id': 'D019954', 'term': 'Neurobehavioral Manifestations'}, {'id': 'D009461', 'term': 'Neurologic Manifestations'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D012816', 'term': 'Signs and Symptoms'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'silvia.giuli@medtronic.com', 'phone': '003932814224', 'title': 'Silvia Giuli', 'organization': 'Medtronic Italia SpA'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Dual Chamber Pacemaker OFF', 'description': 'Implant dual chamber pacemaker programmed ODO (switched OFF)', 'otherNumAtRisk': 39, 'otherNumAffected': 0, 'seriousNumAtRisk': 39, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'Dual Chamber Pacemeker ON', 'description': 'Implant dual chamber pacemaker programmed ON and with Rate Drope Response algorhythm programmed ON', 'otherNumAtRisk': 38, 'otherNumAffected': 2, 'seriousNumAtRisk': 38, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'Atrial arrhythmia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 38, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 38, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Right ventricle lead dislodgment', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 38, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Right atrium lead dislodgment', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 38, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Subclavian vein thrombosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 38, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dead', 'stats': [{'groupId': 'EG000', 'numAtRisk': 39, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 38, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '2'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Syncope Recurrence Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'OG000'}, {'value': '38', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Dual Chamber Pacemaker OFF', 'description': 'Implant dual chamber pacemaker programmed ODO (switched OFF)'}, {'id': 'OG001', 'title': 'Dual Chamber Pacemeker ON', 'description': 'Implant dual chamber pacemaker programmed ON and with Rate Drope Response algorhythm programmed ON'}], 'classes': [{'categories': [{'measurements': [{'value': '57', 'groupId': 'OG000', 'lowerLimit': '40', 'upperLimit': '74'}, {'value': '25', 'groupId': 'OG001', 'lowerLimit': '13', 'upperLimit': '45'}]}]}], 'analyses': [{'pValue': '0.04', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.43', 'ciLowerLimit': '0.19', 'ciUpperLimit': '0.96', 'estimateComment': 'numerator=pacemaker ON denominator=pacemaker OFF', 'groupDescription': 'The analysis was designed to have 80% power to detect a 1-year absolute reduction of 25% in the risk of recurrence of first syncope in the Pm ON arm applying a log-rank test with a 2-sided significance level of 0.05. This analysis was planned as a comparison of the cumulative risk of syncope between the 2 groups with the use of a log-rank test.', 'statisticalMethod': 'Log Rank', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY', 'statisticalComment': 'The risk of syncope recurrence was based on HR obtained by means of the univarate Cox model, with the use of the Breslow method for ties.'}, {'pValue': '0.039', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.43', 'ciLowerLimit': '0.19', 'ciUpperLimit': '0.96', 'pValueComment': 'For the final analysis the threshold of statistical significance was set at 0.04.', 'estimateComment': 'Numerator=pacemaker ON denominator=pacemaker OFF', 'statisticalMethod': 'Log Rank', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE_LEGACY', 'nonInferiorityComment': 'The analysis was designed to have 80% power to detect a 1-year absolute reduction of 25% in the risk of recurrence of first syncope in the treatment arm applying a log-rank test with a 2-sided significance level of 0.05.'}], 'paramType': 'NUMBER', 'timeFrame': '2 years', 'description': 'Intention to treat analysis of percentage of patients with syncope recurrence at 2 years follow-up after study arm assignement', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': '77 patients implanted with dual chamber pacemaker: 39 patients randomized to pacemaker OFF and 38 patients randomized to pacemaker ON'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Dual Chamber Pacemaker OFF', 'description': 'Implant dual chamber pacemaker programmed ODO (switched OFF)'}, {'id': 'FG001', 'title': 'Dual Chamber Pacemeker ON', 'description': 'Implant dual chamber pacemaker programmed ON and with Rate Drope Response algorhythm programmed ON'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '39'}, {'groupId': 'FG001', 'numSubjects': '38'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '39'}, {'groupId': 'FG001', 'numSubjects': '38'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'From April 2007 to April 2011, 89 out of 511 patients (pts) implanted with implantable loop recorder (ILR) documented an asystolic syncope of \\>=3 sec or a non-syncopal asystole of \\>= 6 sec, inclusion criteria to be implanted with a dual chamber pacemaker (PM) and randomized to PM on or PM off. 77 pts out of 89 eligible pts were randomized.', 'preAssignmentDetails': '12 out of 89 eligible pts refused randomization'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '39', 'groupId': 'BG000'}, {'value': '38', 'groupId': 'BG001'}, {'value': '77', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Dual Chamber Pacemaker OFF', 'description': 'Implant dual chamber pacemaker programmed ODO (switched OFF)'}, {'id': 'BG001', 'title': 'Dual Chamber Pacemeker ON', 'description': 'Implant dual chamber pacemaker programmed ON and with Rate Drope Response algorhythm programmed ON'}, {'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': '22', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '39', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '17', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '38', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '63', 'spread': '12', 'groupId': 'BG000'}, {'value': '63', 'spread': '14', 'groupId': 'BG001'}, {'value': '63', 'spread': '13', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '18', 'groupId': 'BG001'}, {'value': '41', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '20', 'groupId': 'BG001'}, {'value': '36', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Italy', 'categories': [{'measurements': [{'value': '20', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '36', 'groupId': 'BG002'}]}]}, {'title': 'Spain', 'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '16', 'groupId': 'BG002'}]}]}, {'title': 'Netherlands', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'Austria', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'Germany', 'categories': [{'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}]}, {'title': 'Canada', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}]}, {'title': 'France', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}]}, {'title': 'Switzerland', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'United Kingdom', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 511}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2006-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-09', 'completionDateStruct': {'date': '2012-11', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-06-30', 'studyFirstSubmitDate': '2006-07-31', 'resultsFirstSubmitDate': '2013-05-22', 'studyFirstSubmitQcDate': '2006-07-31', 'lastUpdatePostDateStruct': {'date': '2025-07-18', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2013-10-24', 'studyFirstPostDateStruct': {'date': '2006-08-01', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-11-18', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Syncope Recurrence Rate', 'timeFrame': '2 years', 'description': 'Intention to treat analysis of percentage of patients with syncope recurrence at 2 years follow-up after study arm assignement'}]}, 'conditionsModule': {'keywords': ['syncope', 'implantable loop recorder'], 'conditions': ['Syncope']}, 'referencesModule': {'references': [{'pmid': '22565936', 'type': 'DERIVED', 'citation': 'Brignole M, Menozzi C, Moya A, Andresen D, Blanc JJ, Krahn AD, Wieling W, Beiras X, Deharo JC, Russo V, Tomaino M, Sutton R; International Study on Syncope of Uncertain Etiology 3 (ISSUE-3) Investigators. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation. 2012 May 29;125(21):2566-71. doi: 10.1161/CIRCULATIONAHA.111.082313. Epub 2012 May 7.'}], 'seeAlsoLinks': [{'url': 'http://www.ncbi.nlm.nih.gov/pubmed/22565936', 'label': 'ISSUE3 main results publication PubMed'}]}, 'descriptionModule': {'briefSummary': 'ISSUE 3 is a multi-center, prospective, randomised controlled double-blind study aimed to assess the effectiveness of pacemaker therapy for prevention of asystolic neurally-mediated syncope.', 'detailedDescription': 'In asystolic neurally-mediated syncope (NMS) documented by Implantable Loop recorder (ILR), ISSUE-2, an observational trial, showed that pacemaker was effective in reducing the 1-year first syncope recurrence rate from 33% rate before implant (ILR phase 1) to 5% rate after implant (phase 2). Moreover, the control non-asystolic group still continued to have a 41% recurrence rate after the first recurrence of syncope, thus supporting the conclusion that the reduction with pacemaker was due to the beneficial effect of pacemaker itself and not to other factors. However a formal controlled trial is needed to confirm these findings.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '40 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Suspected or certain neurally-mediated syncope, based on the Guidelines recently published by the Task Force on Syncope of the European Society of Cardiology 2,3 (Appendix 1);\n* More than 3 syncope episodes in the last 2 years;\n* Clinical presentation of syncope of sufficient severity requiring treatment initiation in the physician's and patient's judgement.\n* Age \\> 40 years.\n* Negative carotid sinus massage.\n* Patients accept to have an ILR implantation.\n\nExclusion criteria:\n\n* Carotid sinus hypersensitivity\n* Suspected or certain heart disease and high likelihood of cardiac syncope:\n* Symptomatic orthostatic hypotension diagnosed by standing blood pressure measurement;\n* Loss of consciousness different from syncope (e.g. epilepsy, psychiatric, metabolic, drop-attack, TIA, intoxication, cataplexy);\n* Subclavian steal syndrome;\n* Psychologically or physically (due to any other illness) or cognitively unfit for participation in the study according to the opinion of the investigator;\n* Patient compliance doubtful;\n* Patient geographically or otherwise inaccessible for follow-up;\n* Patient unwilling or unable to give informed consent;\n* Life expectancy \\<1 year."}, 'identificationModule': {'nctId': 'NCT00359203', 'briefTitle': 'ISSUE3: International Study on Syncope of Uncertain Etiology 3', 'organization': {'class': 'INDUSTRY', 'fullName': 'Medtronic Cardiac Rhythm and Heart Failure'}, 'officialTitle': 'ISSUE3: International Study on Syncope of Uncertain Etiology 3 Pacemaker Therapy for Patients With Asystolic Neurally-mediated Syncope', 'orgStudyIdInfo': {'id': 'ISS3'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Dual chamber pacemaker', 'description': 'Dual chamber pacemaker programmed ODO (switched OFF)', 'interventionNames': ['Device: Dual chamber pacemeker']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Dual chamber pacemeker', 'description': 'Medtronic dual chamber pacemaker programmed ON and with Rate Drope Response programmed ON', 'interventionNames': ['Device: Dual chamber pacemeker']}], 'interventions': [{'name': 'Dual chamber pacemeker', 'type': 'DEVICE', 'otherNames': ['Any model of Medtronic pacemakers with Rate Drop Respons algorhythm:', 'K700, K900, Enpulse, Advisa, Versa'], 'armGroupLabels': ['Dual chamber pacemaker', 'Dual chamber pacemeker']}]}, 'contactsLocationsModule': {'locations': [{'zip': '00165', 'city': 'Rome', 'country': 'Italy', 'facility': 'Medtronic Italia S.p.A.', 'geoPoint': {'lat': 41.89193, 'lon': 12.51133}}], 'overallOfficials': [{'name': 'Michele Brignole, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Ospedali del Tigullio, Lavagna'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Medtronic Cardiac Rhythm and Heart Failure', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}