Catheter-Directed Therapy for Post-Thrombotic Syndrome

(C-TRACT Trial)

Recruiting at14 trial locations

Overseen by Suresh Vedantham, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Washington University School of Medicine

Disqualifiers: Age < 18, Acute DVT, others

No Placebo Group

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if a procedure called EVT, which uses imaging to guide instruments inside blood vessels, can help patients with severe vein blockages from DIO-PTS. The goal is to see if this treatment can reduce symptoms and improve their quality of life.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this treatment for post-thrombotic syndrome?

Research shows that using dedicated venous stents, which are flexible and have strong support, can improve blood flow in patients with post-thrombotic syndrome, leading to better outcomes and higher patency rates (keeping the vein open). ^{1 2 3 4 5}

Is catheter-directed therapy using stents generally safe for humans?

Stents, including drug-eluting and bare-metal types, have been used safely in humans, but they can sometimes cause blood clots (thrombosis) or re-narrowing of the blood vessel (restenosis). Newer stent technologies, like bioresorbable scaffolds, aim to reduce these risks by gradually dissolving and releasing medication to help heal the blood vessel. ^{2 6 7 8 9}

How is catheter-directed therapy for post-thrombotic syndrome different from other treatments?

Catheter-directed therapy for post-thrombotic syndrome is unique because it involves using a catheter to directly deliver treatment to the affected veins, often involving stents that are specifically designed for veins, which are more flexible and have higher radial forces. This approach is minimally invasive and aims to improve blood flow and reduce symptoms by directly targeting the blocked or narrowed veins, unlike traditional treatments that may not address the specific vein obstructions. ^{2 4 10 11 12}

Research Team

Suresh Vedantham, M.D.

Principal Investigator

Clinical Coordinating Center at Washington University School of Medicine

Eligibility Criteria

This trial is for adults with severe post-thrombotic syndrome (PTS) due to a history of deep vein thrombosis, who have leg symptoms or ulcers affecting daily life. They must have documented iliac vein blockage and be able to walk. Excluded are those with less than 6 months to live, previous stents in certain veins, severe allergies to materials used in the procedure, pregnant women, inability to consent or follow-up, certain blood conditions, recent DVTs, severe kidney issues or limb ischemia.

Inclusion Criteria

I have severe post-thrombotic syndrome in my leg that limits my daily activities.

I have a blockage in the vein of my leg documented in the last year.

Subjects must meet BOTH of these Criteria

Exclusion Criteria

I've had a recent deep vein thrombosis (DVT) in the last 3 months.

You have previously had a stent placed in the lower part of the big vein in your abdomen or in the main vein in your leg.

You do not have a moderate or severe post-traumatic stress (PTS) disorder.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either endovascular therapy (EVT) or no-EVT, along with optimal PTS care

6 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with venous clinical severity scores (VCSS) obtained

6 months

Long-term follow-up

Participants enrolled in earlier protocol versions are followed for an extended period to assess long-term outcomes

24 months

Treatment Details

Interventions

• Stents (Stents)

Trial Overview The C-TRACT Trial is testing whether using image-guided endovascular therapy (EVT), which includes placing stents inside veins of the leg can reduce severity of PTS and improve quality of life for patients with disabling venous obstructions after a deep vein thrombosis.

Participant Groups

Group I: Endovascular Therapy - Intervention Experimental Treatment 1 Intervention

All subjects (EVT and No-EVT Arms) will receive optimal PTS care. At each Clinical Center, this will be supervised by a physician experienced in managing PTS. Subjects randomized to EVT will receive the following: 1. imaging-guided iliac vein stent placement, and 2. endovenous ablation of refluxing saphenous vein(s), if the patient has truncal reflux and is still symptomatic. 3. optimal PTS therapy: medical and compression, lifestyle interventions and venous ulcer care

Group II: Non-Endovascular Therapy - Control Active Control 1 Intervention

All subjects will receive optimal PTS care as noted above.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

David H. Perlmutter

Washington University School of Medicine

Chief Executive Officer since 2015

MD from Washington University School of Medicine

Paul Scheel

Washington University School of Medicine

Chief Medical Officer since 2022

MD from Washington University School of Medicine

St. Luke&#39;s Hospital, Kansas City, Missouri

Collaborator

Trials

1

Recruited

250+

Saint Luke's Mid America Heart Institute

Collaborator

Trials

3

Recruited

1,900+

Ontario Clinical Oncology Group (OCOG)

Collaborator

Trials

65

Recruited

42,000+

Dr. Matthew Anderson

Ontario Clinical Oncology Group (OCOG)

Chief Executive Officer since 2020

MD from the University of Toronto

Dr. Chris Simpson

Ontario Clinical Oncology Group (OCOG)

Chief Medical Officer since 2021

MD from Queen's University

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

St. Luke's Hospital, Kansas City, Missouri

Collaborator

Trials

9

Recruited

12,500+

Findings from Research

In a study involving 20 patients with malignant venous obstructions, the use of self-expandable metallic stents successfully relieved symptoms in 16 patients, with complete symptom resolution in 8 cases until death from tumor progression.

The stents were effective in maintaining patency for an average follow-up of three months in 8 patients, demonstrating their utility as a palliative treatment option, despite some complications like thrombotic occlusion and stent migration in a few cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stent implantation as a palliative therapeutic measure in tumor-induced stenoses of the large veins of the body]. Wilhelm, K., Schild, H., Bruch, E., et al.[2016]

Vascular stents have advanced from basic devices to complex drug-delivery systems that can be used in various parts of the body, not just the coronary circulation.

These newer generation stents help prevent complications like neointimal hyperplasia and thrombosis while promoting healthy blood vessel growth, leading to safer and more effective long-term treatments for vascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in stent technology and drug-eluting stents. Nelken, N., Schneider, PA.[2005]

Metallic stents have significantly improved the treatment of arterial and venous diseases through minimally invasive procedures, enabling the treatment of various lesions that were previously difficult or impossible to address.

The article reviews the different types of stents available, highlighting their role in revolutionizing vascular disease management and enhancing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stenting in peripheral vascular disease. Cleveland, TJ., Gaines, P.[2019]

In a study of 200 patients treated with a dedicated sinus-Venous stent, significant clinical improvements were observed, with a decrease in the Villalta score from 10.5 to 5.3, indicating reduced symptoms of post-thrombotic syndrome (PTS) and iliac vein compression syndrome (IVCS).

The stent demonstrated promising patency rates, with primary patency at 68% and secondary patency at 90% over a median follow-up of 12 months, while complications were relatively low, suggesting the stent's effectiveness and safety in treating venous obstructions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patency rates and clinical outcomes in a cohort of 200 patients treated with a dedicated venous stent. van Vuuren, TMAJ., Doganci, S., Wittens, CHA.[2019]

In a study involving 18 patients with post-thrombotic syndrome, both contrast-enhanced MRI (CE-MRI) and non-contrast-enhanced MRI (NCE-MRI) provided similar and clinically insignificant measurements of vein section area, suggesting that NCE-MRI can effectively replace CE-MRI for preoperative evaluations.

However, the study found that measurements from MRI did not correlate well with those obtained from intravascular ultrasound (IVUS), which showed an average difference of 60%, indicating that IVUS remains essential for accurately selecting the appropriate stent size for venous interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Usefulness of non-contrast-enhanced magnetic resonance imaging prior to venous interventions. Kusiak, A., Budzyński, J.[2022]

Bioresorbable scaffolds offer a temporary support for blood vessels, gradually dissolving to reduce the risk of long-term complications associated with permanent metal implants.

These scaffolds are designed to release drugs in a controlled manner, initially providing a high concentration to prevent vascular injuries and excessive tissue growth, which can help in treating conditions like restenosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioresorbable Scaffold-Based Controlled Drug Delivery for Restenosis. Tesfamariam, B.[2020]

Bare-metal stents, while a significant improvement over traditional angioplasty, have a high restenosis rate of about 30%, which can lead to the need for further interventions.

First-generation drug-eluting stents effectively reduce restenosis but are linked to serious late thrombotic events, raising safety concerns; ongoing research aims to develop new stent systems that enhance efficacy while minimizing thrombosis risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparative safety of bare-metal and drug-eluting intracoronary stents. Lambert, ND., Applegate, RJ.[2016]

Surface modification of stainless steel stents with hydrophilic polymers like N-vinylpyrrolidone (NVP) and potassium sulfopropyl acrylate (KSPA) significantly reduces platelet adhesion, which is crucial for preventing blood clots.

In both in vitro and in vivo tests, KSPA-modified stents showed the lowest platelet accumulation, suggesting that this modification could effectively lower the risk of thrombosis in patients using these stents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hydrophilic surface modification of metallic endoluminal stents. Seeger, JM., Ingegno, MD., Bigatan, E., et al.[2019]

Despite advancements in stent technology, including drug-eluting stents, restenosis remains a significant challenge in vascular surgery, indicating that current solutions are not fully effective.

Combining drug-eluting stents with dual antiplatelet therapy has reduced the rates of restenosis and reocclusion, but issues like thrombosis and neointimal hyperplasia still persist in the long term, highlighting the need for further innovations in stent design and drug delivery systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Vascular stents: Approaches used to increase their clinical efficacy]. Kuznetsov, KA., Khar'kova, MV., Karpenko, AA., et al.[2018]

A systematic review of 56 studies involving venous stenting for deep venous obstructions showed a primary patency rate of 82.3% at one year, which decreased to 73.3% at two years, indicating that while stenting is effective, long-term success can be challenging.

Most studies utilized vitamin K antagonists for antithrombotic therapy, but only two studies directly evaluated the impact of this therapy on stent patency, highlighting a significant gap in research regarding the effectiveness of antithrombotic treatments in maintaining stent function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postinterventional antithrombotic management after venous stenting of the iliofemoral tract in acute and chronic thrombosis: A systematic review. Notten, P., Ten Cate, H., Ten Cate-Hoek, AJ.[2023]

Endovenous stenting for post-thrombotic syndrome (PTS) with iliofemoral obstruction shows a high technical success rate of 95% and significant symptom relief, with ulcer healing in about 75% of cases and pain relief in 52%.

Despite the promising outcomes, the overall quality of evidence is rated as 'very low', indicating that while stenting can be effective and has a low risk of complications, further research is needed to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-Analysis of Iliofemoral Stenting for Post-thrombotic Syndrome. Qiu, P., Zha, B., Xu, A., et al.[2019]

The incidence of scaffold thrombosis after bioresorbable vascular scaffold (BVS) implantation was found to be 1.8% at a median follow-up of 1 year, increasing to 0.8% beyond 1 year, indicating a significant risk associated with BVSs over time.

When compared to everolimus-eluting metallic stents (EESs), BVSs showed a 3.4 times higher risk of scaffold thrombosis and also increased risks for myocardial infarction and target lesion revascularization, suggesting that BVSs may not be as safe as EESs in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mid- and Long-Term Outcome Comparisons of Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis. Zhang, XL., Zhu, QQ., Kang, LN., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Stent implantation as a palliative therapeutic measure in tumor-induced stenoses of the large veins of the body]. [2016]

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

Advances in stent technology and drug-eluting stents. [2005]

3. England pubmed.ncbi.nlm.nih.gov

Stenting in peripheral vascular disease. [2019]

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

Patency rates and clinical outcomes in a cohort of 200 patients treated with a dedicated venous stent. [2019]

5. Poland pubmed.ncbi.nlm.nih.gov

Usefulness of non-contrast-enhanced magnetic resonance imaging prior to venous interventions. [2022]

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

Bioresorbable Scaffold-Based Controlled Drug Delivery for Restenosis. [2020]

7. England pubmed.ncbi.nlm.nih.gov

The comparative safety of bare-metal and drug-eluting intracoronary stents. [2016]

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

Hydrophilic surface modification of metallic endoluminal stents. [2019]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Vascular stents: Approaches used to increase their clinical efficacy]. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Postinterventional antithrombotic management after venous stenting of the iliofemoral tract in acute and chronic thrombosis: A systematic review. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Systematic Review and Meta-Analysis of Iliofemoral Stenting for Post-thrombotic Syndrome. [2019]

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

Mid- and Long-Term Outcome Comparisons of Everolimus-Eluting Bioresorbable Scaffolds Versus Everolimus-Eluting Metallic Stents: A Systematic Review and Meta-analysis. [2022]