Positron Emission Tomography (PET) Imaging of Thrombosis

Mass General Brigham

Status and phase: Enrolling; Phase 1

Conditions: COVID-19; Atrial Fibrillation; Thrombosis; Cancer

Treatments: Procedure: Blood Collection; Drug: [64Cu]FBP8; Device: PET/MR; Procedure: Electrocardiogram

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03830320

R01HL109448 (U.S. NIH Grant/Contract)

2015P002385

Details and patient eligibility

About

The purpose of the study is to evaluate a new radiotracer called 64Cu-FBP8 for PET-MR imaging of thrombosis. The tracer has the potential of detecting thrombosis anywhere in the body, for instance in the left atrial appendage of patients with atrial fibrillation, and thereby may provide a non-invasive alternative to the current standard-of-care methods.

Full description

The primary objectives of this study are:

1. To evaluate the safety of [64Cu]FBP8 and its whole body distribution, metabolism, pharmacokinetics, and radiation burden in healthy volunteers.
2. To establish the accuracy of [64Cu]FBP8 -PET to detect left atrial thrombosis in patients with atrial fibrillation.
3. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with COVID-19.
4. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with cancer.
5. To explore the feasibility of [64Cu]FBP8 -PET to detect thrombosis in patients with known or suspicion of thrombus outside of the left atrial appendage.

Enrollment: 165 estimated patients

Sex: All

Ages: 18 to 85 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

For Atrial Fibrillation Patient subjects:

• History of atrial fibrillation or paroxysmal atrial fibrillation;
• Retrospective enrollment: TEE to evaluate LAA within the last 14 days, provided the anticoagulation regimen the patient is on is not changed after the TEE. If a patient has a negative TEE and continues the same stable anti-coagulation regimen he/she is on, then it is extremely unlikely that a new thrombus will develop in the left atrial appendage within the next two weeks. Likewise, if a patient not taking any anti-coagulation has a thrombus in the left atrial appendage, then it is extremely unlikely that this thrombus will resolve spontaneously in the next 14 days if the patient continues not to take any anticoagulation. If the TEE leads to a change being made in the anticoagulation regimen (started/stopped/dose modified), then a time window of 72 hours from the TEE to PET imaging will be used. This scheme will ensure that the TEE can serve as an accurate gold standard;
• Prospective enrollment: TEE to evaluate LAA scheduled in upcoming 14 days;

For COVID-19 Patient subjects:

• Positive test for SARS-CoV-2 RNA detected by RT-PCR collected from the upper or lower respiratory tract analyzed by a certified lab with an FDA approved assay within the last month;
• Patient not requiring mechanical ventilation;

For Cancer Patient subjects:

• Patient is diagnosed with cancer;

For Other Patient subjects:

• Ultrasound- or CT-confirmed or high likelihood of thrombus (e.g., elevated D-dimer)
• Has not received thrombolytics

Exclusion criteria: A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• Subjects less than 18 years of age;
• Electrical implants such as cardiac pacemaker or perfusion pump;
• Pregnant or breastfeeding (a negative STAT quantitative serum hCG pregnancy test is required for females having child-bearing potential before the subject can participate);
• Claustrophobic reactions;
• Subjects will be excluded if research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);
• Unable to lie comfortably on a bed inside the PET scanner;
• Subjects under direct or indirect (i.e. same department as PIs) supervision of the principal investigator;
• Body weight over the weight limit for the moving table (> 300 lbs for the MRI table and >441 lbs for the CT table);
• Metallic or electric implants contraindicated for MR-PET scanning when applicable;
• Does not have the ability to give written informed consent.
• Determined by the investigator(s) to be clinically unsuitable for the study (e.g. based on screening visit and/or during study procedures);

Additional exclusion criteria for Atrial Fibrillation Patient subjects:

• Stroke within the last 3 months;
• Myocardial infarction within the last 3 months;
• Cardiac or major surgery within the last 3 months;
• History of chest pain within the last 6 weeks unless followed by a subsequent stress test or coronary angiography;
• History of syncope within the last 6 weeks;
• Heart rate persistently >120 bpm or persistently < 50 bpm;
• Presence of daytime pauses > 3s

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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165 participants in 5 patient groups

Healthy Volunteers

Active Comparator group

Description:

Twenty (20) healthy adult subjects will be injected with \[64Cu\]FBP8 to establish the safety, whole body distribution, metabolism, pharmacokinetics, and radiation burden of the probe. All subjects will be imaged using PET/MR. Healthy subjects will undergo blood collection before, during, and after the scan. Healthy subjects will also undergo electrocardiogram before and after the scan. An interim review of the data will be conducted after the first six subjects receive the study agent and complete all safety assessments.

Treatment:

Procedure: Electrocardiogram

Procedure: Blood Collection

Device: PET/MR

Drug: [64Cu]FBP8

Atrial Fibrillation Patients

Experimental group

Description:

Thirty-five (35) patients with LAA thrombus documented by TEE will be injected with \[64Cu\]FBP8 and imaged for LAA thrombus with MR-PET. The TEE studies in these patients will be part of their routine clinical care. Thirty-five (35) patients with atrial fibrillation and negative TEE will be injected with \[64Cu\]FBP8 and imaged for LAA thrombus. Forty (40) patients with atrial fibrillation who are scheduled for TEE in the upcoming 14 days will be injected with \[64Cu\]FBP8 and imaged for LAA thrombus.

Treatment:

Device: PET/MR

Drug: [64Cu]FBP8

COVID-19 Patients

Experimental group

Description:

Thirty (30) COVID-19 patients will be injected with \[64Cu\]FBP8 and imaged for thrombi in the body.

Treatment:

Device: PET/MR

Drug: [64Cu]FBP8

Cancer Patients

Experimental group

Description:

Thirty (30) cancer patients will be injected with \[64Cu\]FBP8 and imaged for thrombi in the body.

Treatment:

Device: PET/MR

Drug: [64Cu]FBP8

Other Thrombotic Condition Patients

Experimental group

Description:

Fifty (50) patients with other thrombotic conditions will be injected with \[64Cu\]FBP8 and imaged for thrombi in the body.

Treatment:

Device: PET/MR

Drug: [64Cu]FBP8