Ignite Creation Date:
2025-12-25 @ 12:22 AM
Ignite Modification Date:
2026-01-02 @ 9:13 AM
Study NCT ID:
NCT06736158
Status:
RECRUITING
Last Update Posted:
2025-07-31
First Post:
2024-12-06
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Early Genomic Testing for Inherited Bleeding Disorders
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D020141', 'term': 'Hemostatic Disorders'}, {'id': 'D001778', 'term': 'Blood Coagulation Disorders'}], 'ancestors': [{'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D005820', 'term': 'Genetic Testing'}], 'ancestors': [{'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D005821', 'term': 'Genetic Techniques'}, {'id': 'D033142', 'term': 'Genetic Services'}, {'id': 'D006296', 'term': 'Health Services'}, {'id': 'D005159', 'term': 'Health Care Facilities Workforce and Services'}, {'id': 'D003954', 'term': 'Diagnostic Services'}, {'id': 'D011314', 'term': 'Preventive Health Services'}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'DIAGNOSTIC', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 212}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2025-05-31', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2027-04-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-07-28', 'studyFirstSubmitDate': '2024-12-06', 'studyFirstSubmitQcDate': '2024-12-12', 'lastUpdatePostDateStruct': {'date': '2025-07-31', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-12-16', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Diagnostic yield', 'timeFrame': 'One year', 'description': 'Defined as the proportion of patients who achieve a final diagnosis at one year.'}], 'secondaryOutcomes': [{'measure': 'Time to diagnosis', 'timeFrame': 'One year', 'description': 'The amount of time in weeks and/or months between initial Hematology visit and achieving a diagnosis of an inherited bleeding disorder'}, {'measure': 'Patient Burden', 'timeFrame': 'One year', 'description': 'This will be captured by patient reported survey. Will include data on: number of appointments for diagnosis, number of blood draws, travel (distance, mode, associated costs) and productivity loss questions (e.g. time spent away from work, wages lost, child/elder care costs).'}, {'measure': 'Health Related Quality of Life', 'timeFrame': 'One year', 'description': 'Will be determined using the PROMIS (Patient Reported Outcome Measurement Information System) Profile CAT (Computer Adaptive Testing) v1.0 - 29 for participants 18 and older, and the PROMIS Pediatric Profile GenPop (General Population) v3.0 - Profile-25 for participants 12-17. Each section consists of four items with five-point descriptive scales, except for pain intensity which has a 0-10 numerical rating scale. The sum of the item responses for each multi-item category is converted to a T-score where a score of 50 is the average for the US general population with a standard deviation of 10. Higher scores represent more of something. Therefore, for physical function, higher scores represent better health whereas for anxiety, higher scores represent poorer health.'}, {'measure': 'Cost-effectiveness analysis', 'timeFrame': '2 years', 'description': 'Will be measured by estimating the cost-effectiveness of the early genomic testing pathway compared with the standard diagnostic pathway (cost per diagnosis). This will be done by calculating the costs for each pathway along with the number of cases detected.'}, {'measure': 'Budget Impact Analysis', 'timeFrame': '2 years', 'description': "Economic Impact will be measured by a budget impact analysis. This will be conducted from the healthcare system's perspective using standard techniques. In this model-based analysis, the incremental cost of testing for both the control and intervention arm will be determined, which will allow for detailed analysis on the economic impact of inserting genomic testing at different time points along the diagnostic algorithm."}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['blood coagulation disorders', 'bleeding disorder'], 'conditions': ['Bleeding Disorder']}, 'referencesModule': {'references': [{'pmid': '25196510', 'type': 'BACKGROUND', 'citation': 'Elbatarny M, Mollah S, Grabell J, Bae S, Deforest M, Tuttle A, Hopman W, Clark DS, Mauer AC, Bowman M, Riddel J, Christopherson PA, Montgomery RR; Zimmerman Program Investigators; Rand ML, Coller B, James PD. Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project. Haemophilia. 2014 Nov;20(6):831-5. doi: 10.1111/hae.12503. Epub 2014 Sep 6.'}, {'pmid': '36053176', 'type': 'BACKGROUND', 'citation': 'Castle D, Desborough MJR, Kemp M, Lowe G, Thomas W, Obaji S. Outcomes and management of pregnancy in women with bleeding disorder of unknown cause. J Thromb Haemost. 2022 Nov;20(11):2519-2525. doi: 10.1111/jth.15871. Epub 2022 Sep 21.'}, {'pmid': '32979008', 'type': 'BACKGROUND', 'citation': 'Arya S, Wilton P, Page D, Boma-Fischer L, Floros G, Winikoff R, Teitel J, Dainty K, Sholzberg M. "Everything was blood when it comes to me": Understanding the lived experiences of women with inherited bleeding disorders. J Thromb Haemost. 2020 Dec;18(12):3211-3221. doi: 10.1111/jth.15102. Epub 2020 Oct 21.'}, {'pmid': '31249973', 'type': 'BACKGROUND', 'citation': 'Andres O, Konig EM, Althaus K, Bakchoul T, Bugert P, Eber S, Knofler R, Kunstmann E, Manukjan G, Meyer O, Strauss G, Streif W, Thiele T, Wiegering V, Klopocki E, Schulze H; THROMKIDplus Study Group of the Society of Paediatric Oncology Haematology (Gesellschaft fur Padiatrische Onkologie und Hamatologie, GPOH) and the Society of Thrombosis Haemostasis Research (Gesellschaft fur Thrombose- und Hamostaseforschung, GTH). Use of Targeted High-Throughput Sequencing for Genetic Classification of Patients with Bleeding Diathesis and Suspected Platelet Disorder. TH Open. 2018 Dec 30;2(4):e445-e454. doi: 10.1055/s-0038-1676813. eCollection 2018 Oct.'}, {'pmid': '33079472', 'type': 'BACKGROUND', 'citation': 'Downes K, Borry P, Ericson K, Gomez K, Greinacher A, Lambert M, Leinoe E, Noris P, Van Geet C, Freson K; Subcommittee on Genomics in Thrombosis, Hemostasis. 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Epub 2015 Jul 14.'}, {'pmid': '20626619', 'type': 'BACKGROUND', 'citation': 'Rodeghiero F, Tosetto A, Abshire T, Arnold DM, Coller B, James P, Neunert C, Lillicrap D; ISTH/SSC joint VWF and Perinatal/Pediatric Hemostasis Subcommittees Working Group. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost. 2010 Sep;8(9):2063-5. doi: 10.1111/j.1538-7836.2010.03975.x. No abstract available.'}, {'pmid': '32744769', 'type': 'BACKGROUND', 'citation': 'Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, Carcao M, Mahlangu J, Ragni MV, Windyga J, Llinas A, Goddard NJ, Mohan R, Poonnoose PM, Feldman BM, Lewis SZ, van den Berg HM, Pierce GF; WFH Guidelines for the Management of Hemophilia panelists and co-authors. WFH Guidelines for the Management of Hemophilia, 3rd edition. Haemophilia. 2020 Aug;26 Suppl 6:1-158. doi: 10.1111/hae.14046. Epub 2020 Aug 3. 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Epub 2023 May 8.'}, {'pmid': '26409619', 'type': 'BACKGROUND', 'citation': 'Richter T, Nestler-Parr S, Babela R, Khan ZM, Tesoro T, Molsen E, Hughes DA; International Society for Pharmacoeconomics and Outcomes Research Rare Disease Special Interest Group. Rare Disease Terminology and Definitions-A Systematic Global Review: Report of the ISPOR Rare Disease Special Interest Group. Value Health. 2015 Sep;18(6):906-14. doi: 10.1016/j.jval.2015.05.008. Epub 2015 Aug 18.'}, {'pmid': '17339185', 'type': 'BACKGROUND', 'citation': 'Quiroga T, Goycoolea M, Panes O, Aranda E, Martinez C, Belmont S, Munoz B, Zuniga P, Pereira J, Mezzano D. High prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls. Haematologica. 2007 Mar;92(3):357-65. doi: 10.3324/haematol.10816.'}, {'pmid': '32537805', 'type': 'BACKGROUND', 'citation': 'Srivastava A. Diagnosis of haemophilia and other inherited bleeding disorders - Is a new paradigm needed? Haemophilia. 2021 Feb;27 Suppl 3:14-20. doi: 10.1111/hae.14042. Epub 2020 Jun 14.'}, {'pmid': '40246558', 'type': 'BACKGROUND', 'citation': 'Chaigneau M, Bowman M, Grabell J, Conboy M, Johnson A, Thorpe K, Guerin A, Dinchong R, Paterson A, Good D, Mahar A, Callum J, Wheaton L, Leung J, Khalife R, Sholzberg M, Lillicrap D, James PD. Genomic testing for bleeding disorders (GT4BD): protocol for a randomised controlled trial evaluating the introduction of whole genome sequencing early in the diagnostic pathway for patients with inherited bleeding disorders as compared with standard of care. BMJ Open. 2025 Apr 17;15(4):e102041. doi: 10.1136/bmjopen-2025-102041.'}]}, 'descriptionModule': {'briefSummary': 'The investigators aim to test the introduction of genomic testing early in the diagnostic pathway for inherited bleeding disorders in patients who have not received a diagnosis after first-line testing.\n\nThe goal of this clinical trial is to test the introduction of genomic testing early in the diagnostic pathway for patients referred to Hematology for a suspected inherited bleeding disorder. The main questions it aims to answer are:\n\n1. Does adding early genomic testing increase the number of patients who are diagnosed?\n2. Does adding early genomic testing decrease the overall time to diagnosis?\n3. Is it cost-effective to include early genomic testing in the diagnostic pathway?\n\nThe investigators will compare with a control group of participants who are receiving standard care (no early genomic testing).\n\nParticipants will randomized to a standardized diagnostic testing plus early genomic testing group or to the standardized diagnostic testing group only (with the possibility of being offered genomic testing after 1 year in the study).', 'detailedDescription': 'With the current standardized diagnostic testing process up to 50% of people referred with significant bleeding symptoms will be classified as bleeding disorder of unknown cause (BDUC), defined as those with a positive bleeding score but in whom all current diagnostic test results are repeatedly normal. Incorporating genomic testing early in the diagnostic pathway could significantly improve diagnostic yield, reduce diagnostic delay, alleviate patient anxiety, and allow for more prompt symptom recognition and targeted treatment.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '12 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* New patient referred for abnormal bleeding.\n* Hemostasis expert clinician determined abnormal bleeding history AND family history of bleeding\n* OR no family history of bleeding but hemostasis expert clinician determined severe bleeding history.\n\nExclusion Criteria:\n\n* Prior diagnosis of an inherited bleeding disorder.\n* Acquired cause of bleeding (i.e., medication known to cause bleeding, significant renal or hepatic disease)'}, 'identificationModule': {'nctId': 'NCT06736158', 'acronym': 'GT4BD', 'briefTitle': 'Early Genomic Testing for Inherited Bleeding Disorders', 'organization': {'class': 'OTHER', 'fullName': "Queen's University"}, 'officialTitle': 'Early Genomic Testing for Inherited Bleeding Disorders in Patients Without a Diagnosis After First Line Testing: a Randomized Controlled Trial', 'orgStudyIdInfo': {'id': '4909'}, 'secondaryIdInfos': [{'id': 'RDP-193724', 'type': 'OTHER_GRANT', 'domain': 'Canadian Institutes of Health Research'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Early Genomic Testing Diagnostic Pathway', 'description': 'Participants will receive early genomic testing in addition to standard diagnostic testing.', 'interventionNames': ['Genetic: Genetic testing for inherited bleeding disorders']}, {'type': 'NO_INTERVENTION', 'label': 'Standard Diagnostic Pathway', 'description': 'Participants will receive standard diagnostic testing with the option of receiving genomic testing after 12 months.'}], 'interventions': [{'name': 'Genetic testing for inherited bleeding disorders', 'type': 'GENETIC', 'description': 'Gene panel for bleeding: This analysis will look at a list of genes known to be associated with rare coagulation, platelet, connective tissue, and bleeding disorders. There are currently 318 genes on the panel however this list may be updated throughout the study. Genes of study include those on the the International Society of Thrombosis and Haemostasis (ISTH) TIER-1 (the first group of genes are the diagnostic-grade) and TIER-2 gene list, as well as additional genes identified in published research.', 'armGroupLabels': ['Early Genomic Testing Diagnostic Pathway']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'K7L 3N6', 'city': 'Kingston', 'state': 'Ontario', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Julie Grabell, CCRP', 'role': 'CONTACT', 'email': 'grabell@queensu.ca', 'phone': '+16135336000', 'phoneExt': '75223'}, {'name': 'Megan Chaigneau, RN', 'role': 'CONTACT', 'email': 'megan.chaigneau@queensu.ca', 'phone': '+16135336000', 'phoneExt': '75223'}, {'name': 'Paula D James, MD, FRCPC', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': "Queen's University/Kingston Health Sciences Centre", 'geoPoint': {'lat': 44.22976, 'lon': -76.48098}}, {'zip': 'K8N 1J4', 'city': 'Ottawa', 'state': 'Ontario', 'status': 'RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Amanda Pecarskie', 'role': 'CONTACT', 'email': 'apecarskie@ohri.ca', 'phone': '+16137378899'}, {'name': 'Roy Khalifé, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'The Ottawa Hospital', 'geoPoint': {'lat': 45.41117, 'lon': -75.69812}}, {'zip': 'M5B 1W8', 'city': 'Toronto', 'state': 'Ontario', 'status': 'NOT_YET_RECRUITING', 'country': 'Canada', 'contacts': [{'name': 'Clinical Research Manager', 'role': 'CONTACT', 'email': 'Mercy.charles@unityhealth.to', 'phone': '+1 416-864-5485'}, {'name': 'Michelle Sholzberg, MDCM, FRCPC', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Unity Health', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'centralContacts': [{'name': 'Julie Grabell, CCRP', 'role': 'CONTACT', 'email': 'grabell@queensu.ca', 'phone': '1 613 533 6000', 'phoneExt': '75223'}, {'name': 'Megan Chaigneau, RN', 'role': 'CONTACT', 'email': 'megan.chaigneau@queensu.ca', 'phone': '1 613 533 6000', 'phoneExt': '75223'}], 'overallOfficials': [{'name': 'Paula D James, MD, FRCPC', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Queen's University"}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL'], 'timeFrame': 'IPD and supporting information will be available once manuscript is accepted for publication and will be available indefinitely.', 'ipdSharing': 'YES', 'description': 'all (Individual Participant Data) IPD that underlie results in a publication', 'accessCriteria': 'Access to trial IPD can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA)'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': "Queen's University", 'class': 'OTHER'}, 'collaborators': [{'name': 'Unity Health Toronto', 'class': 'OTHER'}, {'name': 'The Ottawa Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Dr. Paula James', 'investigatorAffiliation': "Queen's University"}}}}