18F-GP1 PET-CT to Detect Bioprosthetic Aortic Valve Thrombosis

Study Overview
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Brief Summary
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18F-GP1 binds with high affinity to the glycoprotein IIb/IIIa receptors on activated platelets. 18F-GP1 PET-CT has recently demonstrated favourable safety, pharmacokinetic, biodistribution and diagnostic performance for the in vivo identification of venous and arterial thrombemboli.

Detailed Description
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Aortic stenosis is the most common reason for valvular interventions in the developed world, with rates projected to increase as the population ages. Aortic valve replacement remains the only recognised treatment available. Bioprostheses are far more common than mechanical prostheses, particularly with increasing rates of transcatheter heart valve use. Bioprothetic valves are less durable than mechanical valves and are subject to deterioration which may lead to clinical heart failure and the need for re-intervention. Long-term results with surgical bioprostheses are well reported, with valve deterioration rates of less than 15% at 10 years. These data, however, rely on re-operation rather than echocardiographic measures, suggesting that the true incidence of structural valve deterioration is underestimated. Valve thrombosis is increasingly recognised as a potential contributor to leaflet degeneration and has been detected in participants undergoing both surgical aortic valve replacement and transcatheter aortic valve implantation. The role of valve thrombosis as an early trigger for calcification and subsequent valve degeneration has not been addressed. The true incidence of valve thrombosis and its impact on clinical outcomes is unknown due to the lack of a sufficiently sensitive non-invasive imaging modality to detect early subclinical thrombosis. Current observational data suggests rates of 12 to 40%, based on computed tomography findings. There is a clinical need for a more sensitive non-invasive method of detecting valve thrombosis.

Official Title
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18F-GP1 Positron Emission Tomography-computed Tomography to Detect Bioprosthetic Aortic Valve Thrombosis; the Biothrombus Study.

Conditions
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Thrombosis Cardiac, Aortic Valve Disease

Intervention / Treatment
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* Diagnostic Test: 18F-GP1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ability to give informed consent >1 month post-surgical or transcatheter aortic valve replacement Exclusion Criteria: Inability to give informed consent Pregnancy or breastfeeding Contraindications to iodinated contrast Contraindications to anticoagulation Use of anticoagulants during the post-operative period prior to screening Extreme claustrophobia Chronic kidney disease (with estimated glomerular filtration rate <30 mL/min/1.73m2) Metastatic malignancy Inability to tolerate the supine position

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bioprosthetic aortic valve<br>Single 18F-GP1 PET-CT | Diagnostic Test: 18F-GP1<br>* 18F-GP1 PET-CT scan<br>|
| Bioprosthetic aortic valve thrombus - repeat imaging<br>18F-GP1 PET-CT at baseline and 3 months | Diagnostic Test: 18F-GP1<br>* 18F-GP1 PET-CT scan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of 18F-GP1 PET-CT bioprosthetic aortic valve uptake | Prevalence of 18F-GP1 PET-CT bioprosthetic aortic valve uptake as measured by standardised uptake values. | 2 years | 
| Intensity of 18F-GP1 PET-CT activity in bioprosthetic aortic valve thrombus | Intensity of 18F-GP1 PET-CT activity in bioprosthetic aortic valve thrombus compared to blood pool as measured by standardised uptake values. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 18F-GP1 PET-CT bioprosthetic aortic valve uptake in patients with thrombus. | 18F-GP1 PET-CT bioprosthetic aortic valve uptake after 3 months in patients with evidence of thrombus at baseline as measured by standardised uptake values. | 2 years |