PET Fibrin Imaging of DVT and PE

This study aims to investigate a novel positron emission tomography(PET)-probe for imaging of fresh intravascular blood clots in pulmonary embolism (PE) and deep venous thrombosis (DVT).

Study Overview

• Status: Recruiting
• Conditions: Deep Vein Thrombosis; Venous Thromboembolism; Pulmonary Embolism
• Intervention / Treatment: Drug: 64Cu-FBP8; Diagnostic test: PET-CT imaging

Detailed Description

Venous thromboembolism (VTE) is one of the most common causes of death in the United States, resulting in more than 100,000 deaths annually. Current diagnostic techniques rely on indirect measures of clot for diagnosis and therefore suffer from the problems of both under and overdiagnosis and cannot always be performed on patients with renal failure and lung disease. In this study, we will use the novel fibrin-specific probe 64CU-FBP8 (Copper-64 labeled fibrin binding probe 8) for PET imaging of fresh blood clots in PE and DVT. Our long-term goal is to establish a novel thrombus body scan (TBS) using 64CU-FBP8 for PET imaging to overcome the limitations of indirect venous thromboembolism diagnosis, and, with one single test, provide a total-body assessment of fresh intravascular clot.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Tilo Winkler, PhD; Phone Number: 617-724-4083; Email: twinkler@mgh.harvard.edu
• Study Contact Backup: Name: Mamary T Kone, MD, MPH; Phone Number: 617-726-1082; Email: mkone@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Tilo Winkler, PhD; Phone Number: 617-724-4083; Email: twinkler@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age or older with a clinically significant pulmonary embolus (PE) confirmed by a filling defect in CT angiography (CTA), and
• Subjects must receive the radiotracer injection within 72 hours of their diagnosis.

Exclusion Criteria:

• Subjects < 18 years of age
• Time of expected radiotracer injection > 72 hours from the time of a positive venous duplex ultrasound or CT- angiogram
• Women subjects of childbearing potential who are pregnant, seeking to become pregnant, or have a positive serum pregnancy (beta-HCG) test
• Unable to lie flat for 45 minutes as assessed by physical examination and medical history (e.g. back pain, arthritis, dyspnea),
• Weight that exceeds the PET camera table limit (300 kg)
• The subject will not be enrolled in the study if the radiation exposure for research studies during the prior 12 months, combined with the exposure from this study would exceed 50 mSv (millisievert).
• Due to the radiation exposure from imaging studies, all women of childbearing potential will be required to have a negative serum pregnancy test performed prior to any imaging procedures on the same day (if not already done that day). Patients with a positive serum pregnancy test will be excluded. Breast feeding women will also be excluded.
• A pre-existing condition or use of a medication including vasopressors and tPA (tissue Plasminogen Activator) that in the opinion of the investigator may place the subject at a substantially increased risk
• Hemodynamic instability, including requiring escalating doses of vasopressor medication.
• No groups designated as "special vulnerable populations" will be studied.
• No exclusions will be made based on race, sex, or ethnic origin.
• 64Cu-FBP8 (Copper-64 labeled fibrin binding probe 8) is cleared by the kidneys, patients with eGFR (estimated Glomerular Filtration Rate ) < 30 will be excluded.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute pulmonary embolism; Subjects will receive 64Cu-FBP8 and undergo PET-CT imaging.	Drug: 64Cu-FBP8; Up to 10 mCi (millicurie) 64Cu-FBP8 will be administered to each subject.; Diagnostic test: PET-CT imaging; All subjects will undergo PET-CT imaging after administration of 64Cu-FBP8.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Location of the thrombus within the lungs	To determine the location of the thrombus regions of interest (ROIs) within the lungs using PET-CT imaging in comparison to the ROI of filling defects on CT-angiogram.	4 hours
Location of clot burden measurements within the thigh	To determine the location of the thrombus ROI within the thigh using PET-CT imaging in comparison to the clot on venous duplex ultrasound.	4 hours
Assessment of 64Cu-FBP8 fibrin activity in the pelvic and upper extremity	The prevalence of high 64Cu-FBP8 fibrin activity in the pelvic ROI and upper extremity ROI's will be reported.	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between normalized 64Cu-FBP8 fibrin activity and plasma D-dimer	Correlation of the total fibrin activity in the imaged fields, excluding the liver, gallbladder, kidneys and urinary bladder normalized by injected dose with the plasma D-dimer.	4 hours
Overall clot burden within the lungs	Overall clot burden calculated as sum of 64Cu-FBP8 activity within a thrombus ROI(s) within the lungs.	4 hours
Overall clot burden within the thigh	Overall clot burden calculated as sum of 64Cu-FBP8 activity within a thrombus ROI(s) within the thigh.	4 hours

Collaborators and Investigators

• Sponsor: Peter Caravan
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Tilo Winkler, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2019
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: July 10, 2019
• First Submitted That Met QC Criteria: July 15, 2019
• First Posted (Actual): July 17, 2019

Study Record Updates

• Last Update Posted (Actual): December 6, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism
• Other Study ID Numbers: 2018P000523

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No