Early Genomic Testing for Inherited Bleeding Disorders

Not Applicable

Not yet recruiting

• Conditions: Bleeding Disorder

• Registration Number: NCT06736158
• Lead Sponsor: Kingston Health Sciences Centre

Brief Summary

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).

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 Timeline

• Study First Submitted: 2024-12-06
• Study First Submitted QC: 2024-12-12
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-21
• Study First Posted: 2025-03-25
• Last Update Posted: 2025-03-26
• Study Start: 2025-04-15
• Primary Completion: 2026-12-31
• Study Completion: 2027-04-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 212

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Diagnostic yield	One year	Defined as the proportion of patients who achieve a final diagnosis at one year.

Secondary Outcome Measures

Name	Time	Method
Time to diagnosis	One year	The amount of time in weeks and/or months between initial Hematology visit and achieving a diagnosis of an inherited bleeding disorder
Patient Burden	One year	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). This will be captured by patient reported survey.
Health Related Quality of Life	One year	Will be determined using the PROMIS (Patient Reported Outcome Measurement Information System) Profile CAT v1.0 - 29 for participants 18 and older, and the PROMIS Pediatric Profile GenPop 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.
Cost-effectiveness analysis	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.
Economic Impact	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.

Trial Locations

Locations (3)

Queen's University/Kingston Health Sciences Centre; 🇨🇦 Kingston, Ontario, Canada

The Ottawa Hospital; 🇨🇦 Ottawa, Ontario, Canada

Unity Health; 🇨🇦 Toronto, Ontario, Canada