Nctid:
NCT06224452
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-10-02"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D000019337", "term"=>"Hematologic Neoplasms"}, {"id"=>"D000001281", "term"=>"Atrial Fibrillation"}], "ancestors"=>[{"id"=>"D000001145", "term"=>"Arrhythmias, Cardiac"}, {"id"=>"D000006331", "term"=>"Heart Diseases"}, {"id"=>"D000002318", "term"=>"Cardiovascular Diseases"}, {"id"=>"D000010335", "term"=>"Pathologic Processes"}, {"id"=>"D000009369", "term"=>"Neoplasms"}, {"id"=>"D000009371", "term"=>"Neoplasms by Site"}, {"id"=>"D000006402", "term"=>"Hematologic Diseases"}], "browseLeaves"=>[{"id"=>"M4586", "name"=>"Atrial Fibrillation", "asFound"=>"Atrial Fibrillation", "relevance"=>"HIGH"}, {"id"=>"M21314", "name"=>"Hematologic Neoplasms", "asFound"=>"Hematological Malignancies", "relevance"=>"HIGH"}, {"id"=>"M4453", "name"=>"Arrhythmias, Cardiac", "relevance"=>"LOW"}, {"id"=>"M9419", "name"=>"Heart Diseases", "relevance"=>"LOW"}, {"id"=>"M9490", "name"=>"Hematologic Diseases", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Heart and Blood Diseases", "abbrev"=>"BC14"}, {"name"=>"Symptoms and General Pathology", "abbrev"=>"BC23"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Neoplasms", "abbrev"=>"BC04"}, {"name"=>"Blood and Lymph Conditions", "abbrev"=>"BC15"}]}, "interventionBrowseModule"=>{"meshes"=>[{"id"=>"C000551803", "term"=>"Ibrutinib"}], "ancestors"=>[{"id"=>"D000092004", "term"=>"Tyrosine Kinase Inhibitors"}, {"id"=>"D000047428", "term"=>"Protein Kinase Inhibitors"}, {"id"=>"D000004791", "term"=>"Enzyme Inhibitors"}, {"id"=>"D000045504", "term"=>"Molecular Mechanisms of Pharmacological Action"}], "browseLeaves"=>[{"id"=>"M42179", "name"=>"Ibrutinib", "asFound"=>"Perioperative", "relevance"=>"HIGH"}, {"id"=>"M2889", "name"=>"Tyrosine Kinase Inhibitors", "relevance"=>"LOW"}, {"id"=>"M25820", "name"=>"Protein Kinase Inhibitors", "relevance"=>"LOW"}, {"id"=>"M7951", "name"=>"Enzyme Inhibitors", "relevance"=>"LOW"}, {"id"=>"T22", "name"=>"Tyrosine", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"All Drugs and Chemicals", "abbrev"=>"All"}, {"name"=>"Amino Acids", "abbrev"=>"AA"}]}}, "protocolSection"=>{"designModule"=>{"studyType"=>"OBSERVATIONAL", "designInfo"=>{"timePerspective"=>"RETROSPECTIVE", "observationalModel"=>"OTHER"}, "enrollmentInfo"=>{"type"=>"ESTIMATED", "count"=>18000}, "patientRegistry"=>false}, "statusModule"=>{"overallStatus"=>"NOT_YET_RECRUITING", "startDateStruct"=>{"date"=>"2024-03-01", "type"=>"ESTIMATED"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2024-01", "completionDateStruct"=>{"date"=>"2024-07-01", "type"=>"ESTIMATED"}, "lastUpdateSubmitDate"=>"2024-03-04", "studyFirstSubmitDate"=>"2024-01-16", "studyFirstSubmitQcDate"=>"2024-01-24", "lastUpdatePostDateStruct"=>{"date"=>"2024-03-05", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"2024-01-25", "type"=>"ACTUAL"}, "primaryCompletionDateStruct"=>{"date"=>"2024-05-01", "type"=>"ESTIMATED"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"to determine the influence of ibrutinib dosing on IRAF reporting. Results were expressed as 2-by2 comparisons against the lowest dosing regimen (140mg/day).", "timeFrame"=>"Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023", "description"=>"Disproportionality estimates will be perform using both univariate and multivariate analyses and a global p-value will measure the difference between dosing regimen"}], "secondaryOutcomes"=>[{"measure"=>"Description of ibrutinib-related atrial fibrillation cases", "timeFrame"=>"Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023", "description"=>"Clinical caracteristics of ibrutinib-related atrial fibrillation cases (sex, age, time to onset, hematological malignacy, coreported drugs, coreported adverse events)"}, {"measure"=>"To determine the influence of ibrutinib dosing on IRAF reporting after exclusion of IRAF cases containing concurrent anticoagulant and/or antiarrhythmic drugs, assuming this approach could exclude reports with history of AF preceding IRAF reporting", "timeFrame"=>"Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023", "description"=>"Disproportionality estimates will be perform both univariate and multivariate analysesand a global p-value will measure the difference between dosing regimen"}, {"measure"=>"To determine the influence of ibrutinib dosing on IRAF reporting according to the underlying chronic B-cell malignancy indication.", "timeFrame"=>"Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023", "description"=>"Disproportionality estimates will be perform using both univariate and multivariate analyses and a global p-value will measure the difference between dosing regimen"}, {"measure"=>"To determine if the time to IRAF onset is dependent of the ibrutinib dosing regimen", "timeFrame"=>"Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023", "description"=>"We will use a linear regression to test if the association between ibrutinib-related atrial fibrillation reporting and time to onset is dependent of the dose regimen (the 140 mg/day ibrutinib dosing regimen will set as the reference)"}, {"measure"=>"Sensitivity analysis will also be performed regarding the influence of ibrutinib dosing on 2 dose-dependent ADRs (neutropenia and thrombocytopenia) reporting related to ibrutinib exposure", "timeFrame"=>"Cases reported in the World Health Organization (WHO) of individual safety case reports to 26th July 2023", "description"=>"Disproportionality estimates will be perform using univariate analysis and a global p-value will measure the difference between dosing regimen"}]}, "oversightModule"=>{"isUsExport"=>false, "oversightHasDmc"=>false, "isFdaRegulatedDrug"=>true, "isFdaRegulatedDevice"=>false}, "conditionsModule"=>{"conditions"=>["Hematological Malignancy", "Atrial Fibrillation"]}, "descriptionModule"=>{"briefSummary"=>"Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has recently revolutionized the treatment of various chronic B-cell malignancies and particularly chronic lymphocytic leukemia (CLL). Atrial fibrillation (AF) has early emerged as a cardiovascular adverse effect (CVAE) of ibrutinib but underlying mechanisms of IRAF are not fully understood.\n\nWhile a dose-reduction or an interruption of ibrutinib is mentioned in the summary of product characteristics of ibrutinib, any beneficial effect on IRAF management of such a management is unclear.\n\nThe main aim of this study is to determine if IRAF is a dose-dependent CVAE in chronic B-cell malignancies patients by studying the association between ibrutinib dose and IRAF reporting in Vigibase®, the World Health Organization (WHO) pharmacovigilance database.", "detailedDescription"=>"Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK), has recently revolutionized the treatment of various chronic B-cell malignancies and particularly chronic lymphocytic leukemia (CLL). Atrial fibrillation (AF) has early emerged as a cardiovascular adverse effect (CVAE) of ibrutinib. In phase 3 randomized clinical trials (RCT), ibrutinib exhibits a ≈4-fold increase-risk of AF compared with controls (pooled relative-risk (RR) 3.9; 95% confidence interval (CI): (2.0-7.5); p\\<0.0001). The annualized incidence rate of ibrutinib-related AF (IRAF) reporting in clinical trials is estimated to 4.9 (95% CI: 2.9-8.3) per 100 person-years. IRAF risk persists throughout ibrutinib exposition and seems to be cumulative with the extension of follow-up and cardiac monitoring.\n\nUnderlying mechanisms of IRAF are not fully understood. Ibrutinib potently inhibits multiple off-target kinases at therapeutic concentrations.\n\nWhile a dose-reduction or an interruption of ibrutinib is mentioned in the summary of product characteristics of ibrutinib, any beneficial effect on IRAF management of such a management is unclear.\n\nThe main aim of this study is to determine if IRAF is a dose-dependent CVAE in chronic B-cell malignancies patients by studying the association between ibrutinib dose and IRAF reporting in Vigibase®, the World Health Organization (WHO) pharmacovigilance database."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["ADULT", "OLDER_ADULT"], "minimumAge"=>"18 years", "samplingMethod"=>"NON_PROBABILITY_SAMPLE", "studyPopulation"=>"* ibrutinib-related atrial fibrillation reports in Vigibase at the time of data extraction\n* involving adult patients\n* with an available ibrutinib daily dose", "eligibilityCriteria"=>"Inclusion Criteria:\n\n* ibrutinib-related atrial fibrillation reports in Vigibase at the time of data extraction\n* involving adult patients\n* with an available ibrutinib daily dose\n\nExclusion Criteria:\n\n* minors\n* no ibrutinib dose available"}, "identificationModule"=>{"nctId"=>"NCT06224452", "briefTitle"=>"Is Ibrutinib-related Atrial Fibrillation Dose Dependent", "organization"=>{"class"=>"OTHER", "fullName"=>"University Hospital, Caen"}, "officialTitle"=>"Is Ibrutinib-related Atrial Fibrillation Dose Dependent: Insights From the WHO Pharmacovigilance Database", "orgStudyIdInfo"=>{"id"=>"Pharmaco011624"}}, "armsInterventionsModule"=>{"interventions"=>[{"name"=>"ibrutinib exposure", "type"=>"DRUG", "description"=>"We will extract all atrial fibrillation cases involving adult patients associated with ibrutinib exposure with an available ibrutinib daily dose"}]}, "contactsLocationsModule"=>{"locations"=>[{"city"=>"Caen", "state"=>"Normandie", "country"=>"France", "facility"=>"Caen University Hospital, Department of Pharmacology", "geoPoint"=>{"lat"=>49.18585, "lon"=>-0.35912}}], "centralContacts"=>[{"name"=>"Joachim Alexandre, MD", "role"=>"CONTACT", "email"=>"alexandre-j@chu-caen.fr", "phone"=>"+33231064670"}], "overallOfficials"=>[{"name"=>"Joachim Alexandre, MD", "role"=>"PRINCIPAL_INVESTIGATOR", "affiliation"=>"University Hospital, Caen"}]}, "ipdSharingStatementModule"=>{"ipdSharing"=>"NO", "description"=>"data are extracted from vigibase; data sharement is conditionned to the opinion of the Uppsala Monitoring Centre"}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"University Hospital, Caen", "class"=>"OTHER"}, "responsibleParty"=>{"type"=>"SPONSOR"}}}}
