The CACHE Study: Coronary Artery Care in HaEmophilia

NCT06706206 | Recruiting

• 1 other identifier: 18218
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators will use state-of-the-art imaging to look at heart disease in people with haemophilia. Haemophilia is an inherited disorder in which blood does not clot properly because of lack of a key 'glue' blood component (chemicals known as factor VIII or IX). People with haemophilia are 40% less likely to die of heart disease, but it is not known exactly why this is. Understanding heart disease in people with haemophilia is important because better treatments for haemophilia mean that these patients are now living longer, but doctors still don't know if the risk for heart disease in these patients as they age is the same as that for the general population. If these processes are better understand (perhaps less blood clotting is actually protecting the heart from blockage-causing clots), scientists might be able to reduce the risk of heart attacks for everybody. The UK's first photon-counting detector cardiac CT scanner generates detailed images of the heart and its blood vessels by counting individual X-ray photons. Together with artificial intelligence tools, it is possible to extract a lot of information from these images. As people age, fat is deposited in the vessels which supply blood to the heart which forms plaques. Plaques cause narrowing of the vessels, reducing blood flow to the heart, and can also burst (rupture), leading to a blood clot and heart attack. The new CT scan will show the type and amount of plaques, and quantify the risk of plaque rupture, in people with haemophilia; and the investigators will compare this to people without haemophilia. Understanding the role of factor VIII/IX in heart attacks will improve management of heart disease in people with haemophilia, and may also lead to new prevention and treatment strategies that benefit heart health for everyone.

Conditions

Haemophilia; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (1)

• Occurrence of coronary artery disease detected by coronary CT angiogram among people with haemophilia (PWH) versus control group.

  This is the primary outcome within the primary objective 'to determine whether coronary artery disease (presence of atherosclerotic plaques, type, burden, fat attenuation index (FAI)) in PWH is similar to the control population matched for standard cardiac risk factors.'

  Participant demographics and cardiovascular risk factors to be collected at enrolment for matching PWH and control group. Photon counting CCTA to be performed at enrolment for prevalence of CAD, and quantitative analyses in the secondary outcome.

Secondary Outcomes (2)

• Quantitative analysis of the volume of each plaque component (calcified, non-calcified, low-density plaques) among people with haemophilia (PWH) compared to control group.

  Participant demographics and cardiovascular risk factors to be collected at enrolment for matching PWH and control group. Photon counting CCTA to be performed at enrolment for prevalence of CAD, and quantitative analyses in the secondary outcome.

• Quantitative analysis of fat attenuation index (FAI) among PWH compared to control group.

  Participant demographics and cardiovascular risk factors to be collected at enrolment for matching PWH and control group. Photon counting CCTA to be performed at enrolment for prevalence of CAD, and quantitative analyses in the secondary outcome.

Other Outcomes (5)

• Secondary Objectives (1a): Subgroup analysis to evaluate the influence of haemophilia severity and type on the occurrence of coronary artery disease as detected by CCTA.

  Participant demographics and cardiovascular risk factors to be collected at enrolment for matching PWH and control group. Photon counting CCTA to be performed at enrolment for prevalence of CAD, and quantitative analyses in the secondary outcome.

• Secondary Objectives (1b): Subgroup analysis to evaluate the influence of haemophilia severity and type on the volume of each plaque component.

  Participant demographics and cardiovascular risk factors to be collected at enrolment for matching PWH and control group. Photon counting CCTA to be performed at enrolment for prevalence of CAD, and quantitative analyses in the secondary outcome.

• Secondary Objectives (1c): Subgroup analysis to evaluate the influence of haemophilia severity and type on the fat attenuation index (FAI).

  Participant demographics and cardiovascular risk factors to be collected at enrolment for matching PWH and control group. Photon counting CCTA to be performed at enrolment for prevalence of CAD, and quantitative analyses in the secondary outcome.

Interventions

Observational trial OTHER

Observational clinical trial. Participants will undergo cardiovascular risk assessment (clinical and blood tests) and coronary CT angiogram. These results will be compared to a control population without haemophilia (recruited as part of a different clinical trial).

Eligibility Criteria

• Age: 45 Years - 120 Years
• Sex: male
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants must have a diagnosis of haemophilia A or B. Participants must be 45 years or older.

You may qualify if:

• Be willing and able to give informed consent for participation in the study.
• Male, aged 45 years or above (no upper age limit).
• Haemophilia A or B with Factor VIII/IX less than 40% (0.40 IU/ml).

You may not qualify if:

• Participants unable or unwilling to give informed consent.
• Participants unable to understand the English language.
• Participants unable or unwilling to attend for the necessary scans and investigations.
• Patients with absolute contra-indications to CT imaging will be excluded from the study. This includes:
• Any known contraindications to CT iodinated Contrast.
• Significant renal impairment (eGFR \<30 ml/min).
• Any other medical conditions which would influence the reliability of the study results determined by the investigators.

Sponsors & Collaborators

• Oxford University Hospitals NHS Trust: lead

Study Sites (1)

Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Foundation Trust

Oxford, Oxfordshire, OX3 7HE, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Citrated blood samples for research markers of haemostasis/thrombosis, only retained for the duration of the study.

MeSH Terms

Conditions

Hemophilia A; Cardiovascular Diseases

Interventions

Observation

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Central Study Contacts

Susie Shapiro

CONTACT

+44 (0)1865 225316; susie.shapiro@ouh.nhs.uk

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Primary Investigator

Study Record Dates

• First Submitted: November 19, 2024
• First Posted: November 26, 2024
• Study Start: February 25, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2032
• Last Updated: March 11, 2026

Record last verified: 2026-03

Locations

GB (1)