Early Genomic Testing for Inherited Bleeding Disorders (GT4BD)

July 28, 2025 updated by: Dr. Paula James, Queen's University

Early Genomic Testing for Inherited Bleeding Disorders in Patients Without a Diagnosis After First Line Testing: a Randomized Controlled Trial

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.

The 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:

  1. Does adding early genomic testing increase the number of patients who are diagnosed?
  2. Does adding early genomic testing decrease the overall time to diagnosis?
  3. Is it cost-effective to include early genomic testing in the diagnostic pathway?

The investigators will compare with a control group of participants who are receiving standard care (no early genomic testing).

Participants 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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

212

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Kingston, Ontario, Canada, K7L 3N6
        • Recruiting
        • Queen's University/Kingston Health Sciences Centre
        • Contact:
        • Contact:
        • Principal Investigator:
          • Paula D James, MD, FRCPC
      • Ottawa, Ontario, Canada, K8N 1J4
        • Recruiting
        • The Ottawa Hospital
        • Contact:
        • Principal Investigator:
          • Roy Khalifé, MD
      • Toronto, Ontario, Canada, M5B 1W8
        • Not yet recruiting
        • Unity Health
        • Contact:
        • Principal Investigator:
          • Michelle Sholzberg, MDCM, FRCPC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • New patient referred for abnormal bleeding.
  • Hemostasis expert clinician determined abnormal bleeding history AND family history of bleeding
  • OR no family history of bleeding but hemostasis expert clinician determined severe bleeding history.

Exclusion Criteria:

  • Prior diagnosis of an inherited bleeding disorder.
  • Acquired cause of bleeding (i.e., medication known to cause bleeding, significant renal or hepatic disease)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Early Genomic Testing Diagnostic Pathway
Participants will receive early genomic testing in addition to standard diagnostic testing.
Genetic: Genetic testing for inherited bleeding disorders
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.
No Intervention: Standard Diagnostic Pathway
Participants will receive standard diagnostic testing with the option of receiving genomic testing after 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Diagnostic yield
Time Frame: One year
Defined as the proportion of patients who achieve a final diagnosis at one year.
One year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to diagnosis
Time Frame: One year
The amount of time in weeks and/or months between initial Hematology visit and achieving a diagnosis of an inherited bleeding disorder
One year
Cost-effectiveness analysis
Time Frame: 2 years
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.
2 years
Patient Burden
Time Frame: One year
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).
One year
Health Related Quality of Life
Time Frame: One year
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.
One year
Budget Impact Analysis
Time Frame: 2 years
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.
2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Economic Implications
Time Frame: 2 years
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 diagnostic yield.
2 years
Economic Impact
Time Frame: 2 years
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.
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Queen's University

Collaborators

Unity Health Toronto
The Ottawa Hospital

Investigators

  • Principal Investigator: Paula D James, MD, FRCPC, Queen's University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 31, 2025

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

April 30, 2027

Study Registration Dates

First Submitted

December 6, 2024

First Submitted That Met QC Criteria

December 12, 2024

First Posted (Actual)

December 16, 2024

Study Record Updates

Last Update Posted (Actual)

July 31, 2025

Last Update Submitted That Met QC Criteria

July 28, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4909
  • RDP-193724 (Other Grant/Funding Number: Canadian Institutes of Health Research)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

all (Individual Participant Data) IPD that underlie results in a publication

IPD Sharing Time Frame

IPD and supporting information will be available once manuscript is accepted for publication and will be available indefinitely.

IPD Sharing Access Criteria

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)

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Bleeding Disorder

Clinical Trials on Genetic testing for inherited bleeding disorders

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cambodia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe