PET/CT Imaging for Deep Vein Thrombosis

Overseen By Ahmed Tawakol, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Disqualifiers: May-Thurner syndrome, Renal dysfunction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must be able to receive anticoagulation therapy to participate.

Is Yttrium-90 radioembolization generally safe for humans?

Yttrium-90 radioembolization, also known as Selective Internal Radiation Therapy (SIRT), has been used safely for treating liver cancers for over two decades. It is considered a promising and minimally invasive treatment, with its safety confirmed in clinical applications, although it can have complications if not properly managed. ^{1 2 3 4 5}

How does PET/CT imaging differ from other treatments for deep vein thrombosis?

PET/CT imaging is unique because it uses a special type of scan to detect blood clots in the veins before they cause symptoms, which is different from traditional methods that often rely on symptoms to prompt testing. This approach can be particularly useful in cancer patients who are at higher risk for blood clots. ^{6 7 8 9 10}

What is the purpose of this trial?

The goal of this study is to develop strategies that will improve outcomes for patients with deep vein thrombosis (DVT), using in vivo FDG-PET inflammation imaging to better predict the development of the post-thrombotic syndrome (PTS). New approaches are needed to improve the outcomes of patients with DVT, a disease that affects up to 600,000 patients per year in the US alone. DVT acutely places patients at risk of death from pulmonary embolism and causes 50,000 deaths annually in the US. Moreover, up to 30-50% of patients will develop PTS, an illness characterized by inflammation-driven fibrotic vein wall injury, and persistent thrombus obstruction. PTS occurs despite anticoagulant therapy, and produces chronic disability from leg pain, heaviness, edema, skin pigmentation, and ulcers; some patients may even require amputation. PTS impairs quality of life to the same extent as chronic obstructive pulmonary disease or diabetes. Therefore new diagnostic insights into PTS are urgently needed. There are several major challenges to improve outcomes in PTS: A) Limited in vivo knowledge regarding inflammation and the development of PTS; B) L Lack of predictive approaches to identify patients at high risk for PTS that will preferentially benefit from novel therapies. Recently, our laboratories have harnessed FDG-PET molecular imaging to illuminate DVT inflammation in vivo, and to provide a new strategy to diagnose recurrent DVT, a vexing clinical problem (Hara et al. Circulation 2014). We now propose to further develop FDG-PET to improve outcomes in DVT and PTS. The objective of this application is to develop FDG-PET as an inflammation imaging approach to assess DVT inflammation and predict risk of developing PTS in human subjects; Hypothesis 1A: Inflammatory activity in DVT (quantified acutely, using FDG-PET imaging within 0-7 days after DVT) will predict PTS incidence (primary) and severity (secondary) within a 24 month follow-up period. Hypothesis 1B: Inflammatory activity in DVTs (quantified sub-acutely, using FDG-PET imaging within 21-28 days after DVT), will predict PTS incidence and severity. Eighty patients with DVT will be imaged using FDG-PET/CT acutely (0-7 days of DVT diagnosis), and sub-acutely (21-28 days after diagnosis). Subjects will be evaluated repeatedly for up to 2 years to detect clinical evidence of PTS (Villalta score), ultrasound findings for structural venous injury, and soluble biomarkers of systemic inflammation. Subsequently, we will evaluate the relationship between FDG DVT activity and the development of PTS.

Eligibility Criteria

This trial is for individuals over 30 years old who have experienced their first symptomatic, proximal deep vein thrombosis (DVT), with or without concurrent distal DVT or pulmonary embolism. It excludes those with May-Thurner syndrome, life expectancy under 6 months, inability to receive anticoagulation therapy, prior thrombolytic treatment for DVT, symptoms of DVT more than a week before presenting, or renal dysfunction.

Inclusion Criteria

I am over 30 years old.

I have a blood clot in a major vein for the first time, which may also be in my lung.

Exclusion Criteria

I have been diagnosed with May-Thurner syndrome.

You are expected to live for less than 6 months.

My kidney function is reduced with creatinine above 1.5 mg/ml or clearance below 60 ml/min.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Imaging Visit 1

Participants receive a PET/CT scan and contrast-enhanced CT of the lower extremity, and blood labs are drawn

0-7 days after DVT diagnosis

1 visit (in-person)

Imaging Visit 2

Participants receive a PET/CT scan and blood labs are drawn

21-28 days after DVT diagnosis

1 visit (in-person)

Clinical Evaluation 1

Participants are evaluated for symptoms of DVT and PTS, blood labs are drawn, and an ultrasound is performed

6 months after DVT diagnosis

1 visit (in-person)

Clinical Evaluation 2

Participants are evaluated for symptoms of DVT and PTS, blood labs are drawn, and an ultrasound is performed

24 months after DVT diagnosis or time of PTS diagnosis

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Treatment Details

Interventions

• PET/CT

Trial Overview The study aims to use FDG-PET/CT imaging to predict the risk and severity of post-thrombotic syndrome (PTS) in patients with DVT. Eighty participants will undergo PET/CT scans acutely (0-7 days after diagnosis) and sub-acutely (21-28 days later). They'll be monitored for up to two years for PTS signs using clinical scores, ultrasound assessments, and inflammation markers.

Participant Groups

Group I: Single Arm: Observation after Imaging Experimental Treatment 1 Intervention

This is a single-arm study, where subjects will be monitored for development of PTS after baseline non-invasive imaging with FDG PET/CT. The experimental interventIon is the PET/CT imaging.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

Selective internal radiotherapy (SIRT) with yttrium-90 can lead to significant tumor response in patients with hepatic malignancies, allowing for subsequent liver resection in selected cases, as demonstrated by a mean lesion volume reduction of 475 cm³ in 12 patients.

While SIRT is generally safe with no complications noted post-treatment, the study found a 67% morbidity rate and 11% mortality rate within 90 days after surgery, highlighting the need for careful patient selection and further research to optimize outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90: Safety and Outcomes. Mafeld, S., Littler, P., Hayhurst, H., et al.[2020]

In a study of 825 patients with liver malignancies, most extrahepatic shunts causing complications during Selective Internal Radiation Therapy (SIRT) with Y-90 were identified using hepatic digital subtraction angiography (DSA).

However, SPECT/CT imaging revealed additional shunts in 6.5% of patients, leading to further interventions and preventing SIRT in some cases, highlighting the importance of combining imaging techniques for better patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioembolization with Y-90 Glass Microspheres: Do We Really Need SPECT-CT to Identify Extrahepatic Shunts? Theysohn, JM., Ruhlmann, M., Müller, S., et al.[2018]

The study highlights the feasibility of using PET/MR imaging for assessing biodistribution and dosimetry in liver selective internal radiotherapy (SIRT), which is important for effective radionuclide therapies.

PET/MR offers advantages over traditional PET/CT, including better lesion detection and reduced radiation exposure, making it a promising tool for repeated imaging in SIRT dosimetry.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

90Yttrium PET/MR-based dosimetry after liver radioembolization (SIRT). Wissmeyer, M., Delattre, BM., Zaidi, H., et al.[2018]

In a study of 212 patients treated with outpatient SIRT (90Y-microspheres) for liver cancers, only 3.3% experienced serious adverse events that required hospitalization, indicating a high safety profile for this treatment.

The average radiation exposure from the treatment was low, with a mean dose rate of 1.88 µSv/h, which is below the national safety threshold for outpatient procedures, further supporting the safety of SIRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outpatient Yttrium-90 microsphere radioembolization: assessment of radiation safety and quantification of post-treatment adverse events causing hospitalization. Aberle, S., Kenkel, D., Becker, AS., et al.[2020]

Selective internal yttrium-90 radioembolization therapy ((90)Y-SIRT) is an effective and safe minimally invasive treatment for liver malignant tumors, supported by clinical applications over the past two decades and recognized by major cancer treatment guidelines.

A consensus was formed by experts from various medical fields to standardize the management and treatment procedures for (90)Y-SIRT, addressing critical aspects such as indications, contraindications, postoperative follow-up, and radiation safety, to enhance treatment safety and success rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chinese expert consensus on selective internal radiation therapy with yttrium-90 for primary and metastatic hepatocellular carcinoma]. [2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Liver Resection After Selective Internal Radiation Therapy with Yttrium-90: Safety and Outcomes. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Radioembolization with Y-90 Glass Microspheres: Do We Really Need SPECT-CT to Identify Extrahepatic Shunts? [2018]

3. United States pubmed.ncbi.nlm.nih.gov

90Yttrium PET/MR-based dosimetry after liver radioembolization (SIRT). [2018]

4. Italy pubmed.ncbi.nlm.nih.gov

Outpatient Yttrium-90 microsphere radioembolization: assessment of radiation safety and quantification of post-treatment adverse events causing hospitalization. [2020]

5. China pubmed.ncbi.nlm.nih.gov

[Chinese expert consensus on selective internal radiation therapy with yttrium-90 for primary and metastatic hepatocellular carcinoma]. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Venous thromboembolism detected by FDG-PET/CT in cancer patients: a common, yet life-threatening observation. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

The role of 18F-FDG PET/CT in differentiating malignant from benign portal vein thrombosis. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

The feasibility of contrast-enhanced CT to identify the adhesive renal venous tumor thrombus of renal cell carcinoma. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Detecting deep venous thrombosis with technetium-99m-labeled synthetic peptide P280. [2016]

10. United States pubmed.ncbi.nlm.nih.gov

Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT). [2022]