Catheter-directed Thrombolysis Compared to Anticoagulation Alone for Acute Primary Iliofemoral Deep Venous Thrombosis

Study Overview
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Brief Summary
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Post-thrombotic syndrome (PTS) is a complication that can develop after deep vein thrombosis (DVT) of the lower extremities. PTS can occur at various times after the initial episode, but usually manifests within two years of initial DVT onset. Early and more complete thrombus clearance is believed by many to relieve venous outflow obstruction, preserve valvular function and reduce venous hypertension. Two previously published randomized controlled trials, the CAVENT trial and the ATTRACT trial, were larger and designed to investigate the efficacy of CDT. However, both of these trials included patients with iliofemoral as well as femoro-popliteal deep vein thrombosis. Our study will be limited to patients with iliofemoral deep vein thrombosis to assess whether Pharmacomechanical catheter-directed thrombolysis (PCDT) therapy utilizing AngioJet and tPA can safely and effectively reduce post thrombotic syndrome after 24 months.

Detailed Description
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Patients with Iliofemoral DVT are theoretically at the highest risk for development of PRS given involvement of the major drainage pathway of both superficial femoral and deep femoral veins. This would not only affect the primary venous drainage, but would also compromise the ability to develop efficient collateral pathways. This creates higher chances of developing post-thrombotic syndrome (PTS). The proposed trial would utilize Angiojet thrombectomy followed by catheter directed thrombolysis and Anticoagulation compared to Anticoagulation alone. To assess whether Pharmacomechanical catheter-directed thrombolysis (PCDT) therapy utilizing AngioJet and tPA for the treatment of iliofemoral deep venous thrombosis can safely and effectively reduce post thrombotic syndrome after 24 months.

Official Title
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Pharmacomechanical Catheter-directed Thrombolysis (PCDT) Plus Anticoagulation Compared to Anticoagulation Alone for Acute Primary Iliofemoral Deep Venous Thrombosis:

Conditions
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Deep Venous Thrombosis, Post Thrombotic Syndrome

Intervention / Treatment
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* Combination Product: Catheter directed thrombolysis plus anticoagulation
* Drug: Anticoagulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age>18 and younger than 75 Symptomatic, proximal deep-vein thrombosis involving the Iliofemoral vein from 12/01/2019 to 12/01/2022 Exclusion Criteria: Age less than 18 years or greater than 75 years. Symptom duration > 14 days for the DVT episode in the index leg (i.e. non-acute DVT). In the index leg: established PTS, or previous symptomatic DVT within the last 2 years. In the contralateral (non-index) leg: symptomatic acute DVT a) involving the popliteal and/or tibial veins; or b) for which thrombolysis is planned as part of initial therapy. Limb-threatening circulatory compromise. PE with hemodynamic compromise (i.e. hypotension). Inability to tolerate PCDT procedure due to severe dyspnea or acute systemic illness. Allergy, hypersensitivity, or thrombocytopenia from heparin, rt-PA, or iodinated contrast, except for mild-moderate contrast allergies for which steroid pre-medication can be used. Hemoglobin < 9.0 mg/dl, INR > 1.6 before warfarin was started, or platelets < 100,000 /ml. Moderate renal impairment in diabetic patients (estimated GFR < 60 ml/min) or severe renal impairment in non-diabetic patients (estimated GFR < 30 ml/min). Active bleeding, recent (< 3 months) GI bleeding, severe liver dysfunction, bleeding diathesis. Recent (< 3 months) internal eye surgery or hemorrhagic retinopathy; recent (< 10 days) major surgery, cataract surgery, trauma, CPR, obstetrical delivery, or other invasive procedure. History of stroke or intracranial/intraspinal bleed, tumor, vascular malformation, aneurysm. Active cancer (metastatic, progressive, or treated within the last 6 months). Exception: patients with non-melanoma primary skin cancers are eligible to participate in the study. Severe hypertension on repeated readings (systolic > 180mmHg or diastolic > 105 mmHg). Pregnant (positive pregnancy test, women of childbearing potential must be tested). Recently (< 2 years or chronic non-ambulatory status. Use of a thienopryridine antiplatelet drug (except clopidogrel) in the last 5 days. Life expectancy < 2 years or chronic non-ambulatory status. Inability to provide informed consent or to comply with study assessments (e.g. due to cognitive impairment or geographic distance).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pharmacomechanical thrombolysis plus anticoagulation<br>This group of patients will receive Pharmacomechanical catheter-directed thrombolysis (PCDT) plus Anticoagulation. PCDT will be AngioJet along with alteplase. Anticoagulation will be heparin only | Combination Product: Catheter directed thrombolysis plus anticoagulation<br>* Patients will be randomized to pharmacomechanical catheter directed thrombolysis plus anticoagulation. PCDT will be AngioJet along with alteplase.<br>* Other names: Pharmacomechanical thrombolysis;|
| Active Comparator: Anticoagulation<br>This group of patients will receive standard anticoagulation only. Anticoagulation will be Heparin only | Drug: Anticoagulation<br>* Patients will receive anticoagulation alone. Anticoagulation will be heparin only.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-thrombotic syndrome at any time between 6-month and 24-month. | Occurrence of post-thrombotic syndrome at any time between 6-month and 24-month after procedure by Villata score (Villata score >5 or more), or if patient underwent an unplanned endovascular procedure to treat venous symptoms. The variables in villata scores are pain, cramps, heaviness, parasthesia, pruritus, pretibial edema, skin induration, hyperpigmentation, pain during calf compression, venous ectasia and redness. The Villata score ranges 0-45. Villata score <5 means no post-thrombotic syndrome. Villata score 5-9 mild post-thrombotic syndrome. Villata score 10-14 means moderate post-thrombotic syndrome. Villata score ≥15 or presence of an ulcer indicates severe post-thrombotic syndrome. The more is the score the worse is the disease. | 6-24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-thrombotic syndrome at 6 months. | Occurrence of post-thrombotic syndrome at 6 months measured by Villata score (Villalta score was 5 or higher). | 6 months | 
| Post-thrombotic syndrome at 12 months. | Occurrence of post-thrombotic syndrome at 12 months measured by Villata score (Villalta score was 5 or higher). | 12 months | 
| Post-thrombotic syndrome at 18 months. | Occurrence of post-thrombotic syndrome at 18 months measured by Villata score (Villalta score was 5 or higher). | 18 months | 
| Post-thrombotic syndrome at 24 months. | Occurrence of post-thrombotic syndrome at 24 months measured by Villata score (Villalta score was 5 or higher). | 24 months | 
| Villalta scale at 6 months | The severity of the post-thrombotic syndrome to be evaluated at 6 months with the use of the Villalta scale | 6 months | 
| Villalta scale at 12 months | The severity of the post-thrombotic syndrome to be evaluated at 12 months with the use of the Villalta scale. | 12 months | 
| Villalta scale at 18 months | The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Villalta scale. | 18 months | 
| Villalta scale at 24 months | The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Villalta scale. | 24 months | 
| Venous Clinical Severity Score at 6 months | The severity of the post-thrombotic syndrome to be evaluated at 6 months with the use of the Venous Clinical Severity Score. | 6 months | 
| Venous Clinical Severity Score at 12 months | The severity of the post-thrombotic syndrome to be evaluated at 12 months with the use of the Venous Clinical Severity Score. | 12 months | 
| Venous Clinical Severity Score at 18 months | The severity of the post-thrombotic syndrome to be evaluated at 18 months with the use of the Venous Clinical Severity Score. | 18 months | 
| Venous Clinical Severity Score at 24 months | The severity of the post-thrombotic syndrome to be evaluated at 24 months with the use of the Venous Clinical Severity Score. | 24 months | 
| Health-Related Quality of Life AT 6 months | Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life | 6 months | 
| Health-Related Quality of Life at 12 months. | Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 12 months. | 12 months | 
| Health-Related Quality of Life at 18 months. | Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 18 months. | 18 months | 
| Health-Related Quality of Life at 24 months. | Health-Related Quality of Life measured by Venous Disease-Specific Quality of Life at 24 months. | 24 months | 
| Health-Related Quality of Life at 6 months. | Health-Related Quality of Life measured by Generic Quality of Life at 6 months. | 6 months | 
| Health-Related Quality of Life at 12 months. | Health-Related Quality of Life measured by Generic Quality of Life at 12 months | 12 months | 
| Health-Related Quality of Life at 18 months. | Health-Related Quality of Life measured by Generic Quality of Life at 18 months. | 18 months | 
| Health-Related Quality of Life at 24 months. | Health-Related Quality of Life measured by Generic Quality of Life at 24 months. | 24 months | 
| Health-Related Quality of Life at 6 months. | Health-Related Quality of Life measured by Administration of QOL Measures at 6 months. | 6 months | 
| Health-Related Quality of Life at 12 months. | Health-Related Quality of Life measured by Administration of QOL Measures at 12 months. | 12 months | 
| Health-Related Quality of Life at 18 months. | Health-Related Quality of Life measured by Administration of QOL Measures at 18 months. | 18 months | 
| Health-Related Quality of Life at 24 months. | Health-Related Quality of Life measured by Administration of QOL Measures at 24 months. | 24 months | 
| Treatment Failures that are Not PTS. | Treatment Failures that are Not PTS (defined as one or more of the following during the 24 months post randomization: 1) the patient underwent an unplanned endovascular or surgical intervention for the treatment of severe symptomatic venous disease in the index leg within the first 24 months after randomization (2) the subject underwent an amputation in the index leg anytime within 24 months after randomization; or (3) the subject developed venous gangrene in the index leg within the first 24 months after randomization. | 6-24 months | 
| Severity of presenting DVT Symptoms at 6 months | Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 6 months | 6 months | 
| Severity of presenting DVT Symptoms at 12 months | Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 12 months | 12 months | 
| Severity of presenting DVT Symptoms at 18 months | Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 18 months | 18 months | 
| Severity of presenting DVT Symptoms at 24 months | Severity of presenting DVT Symptoms (Leg pain severity measured by pain scale) at 24 months | 24 months | 
| Severity of presenting DVT Symptoms at 6 months | Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 6 months | 6 months | 
| Severity of presenting DVT Symptoms at 12 months | Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 12 months | 12 months | 
| Severity of presenting DVT Symptoms at 18 months | Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 18 months | 18 months | 
| Severity of presenting DVT Symptoms at 24 months | Severity of presenting DVT Symptoms (Leg swelling measured by measuring calf swelling) at 24 months | 24 months | 
| Degree of Resolution of Thrombus with PCDT at 6 months. | Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated. | 6 months | 
| Degree of Resolution of Thrombus with PCDT at 12 months. | Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated. | 12 months | 
| Degree of Resolution of Thrombus with PCDT at 18 months. | Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated. | 18 months | 
| Degree of Resolution of Thrombus with PCDT at 24 months. | Degree of Resolution of Thrombus with PCDT (Assessed by two sets of venograms in PCDT arm, one baseline venogram of the proximal veins (popliteal vein through infrarenal IVC) obtained after initial catheter insertion into the venous system before PCDT; and one the final venogram of the proximal veins obtained after PCDT and any adjunctive procedures, before sheath removal. Marder score will be used to quantify clot burden. Marder score range 0-24, with 0 representing no thrombus and 24 representing complete thrombosis). The degree of thrombus elimination (% change in pre-PCDT and post-PCDT Marder score) will be calculated. | 24 months |