Chronic Venous Thrombosis: Relief With Adjunctive Catheter-Directed Therapy (The C-TRACT Trial)

The purpose of this study is to determine if the use of image-guided, endovascular therapy (EVT) is an effective strategy with which to reduce Post Thrombotic Syndrome (PTS) disease severity and improve quality of life in patients with established disabling iliac-obstructive post thrombotic syndrome (DIO-PTS).

The rationale for performing the C-TRACT Trial is based upon:

1. the debilitating life impact of DIO-PTS upon patients, as cited in the U.S. Surgeon General's 2008 Call to Action on DVT (95);
2. the inability of existing therapies to prevent or alleviate most cases of DIO-PTS;
3. the role of iliac vein obstruction and saphenous reflux in causing the severe manifestations of DIO-PTS;
4. the ability of stent placement and endovenous ablation to eliminate obstruction and reflux, respectively, to reduce PTS severity, and to improve QOL in preliminary studies;
5. the risks, costs, and uncertainties of this novel but invasive strategy;
6. the lack of consensus on whether EVT should be used for DIO-PTS;
7. the motivation of our established investigator team to answer this critical clinical question.

We will determine if EVT should be routinely used to treat DIO-PTS. If so, this finding will fundamentally change DIO-PTS practice towards more frequent use of EVT. If EVT proves ineffective or unsafe, this finding will reduce or eliminate the use of potentially risky and expensive procedures.

250 subjects with established DIO-PTS will be randomized in a 1:1 ratio to either EVT or No-EVT treatment groups. All participants will receive standard PTS therapy. Subjects will be enrolled over approximately 36 months in 20-40 U.S. Participants enrolled in C-TRACT protocol versions prior to 5.0 will be followed for 24 months. Subjects enrolled on protocol version 5.0 or after will be followed for 6 months. The study will take approximately 6 years to complete.

Eligibility Criteria:
Inclusion Criteria: Subjects must meet BOTH of these Criteria

1. Disabling (moderate-to-severe) PTS, defined by a) presence of chronic venous disease \> or = 3 months duration in a leg with history of DVT, as determined by the site principal investigator or a physician co-investigator; and b) substantial limitation of daily activities or work capacity due to venous symptoms or an open venous ulcer, per the same investigator.
2. Ipsilateral iliac vein obstruction documented within 12 months prior to screening by either:

   1. Occlusion or \>50% or = 50% stenosis of the iliac vein on venogram, CT venogram, MR venogram, or intravascular ultrasound (IVUS) or
   2. Air plethysmography showing deep venous obstruction of the ipsilateral leg (reduced venous outflow fraction), and ultrasound showing echogenic material in the ipsilateral iliac vein and non-phasic continuous Doppler flow in the ipsilateral common femoral vein (CFV) in the presence of normal phasic Doppler flow in the contralateral CFV.

Exclusion Criteria: Subjects meeting any of these criteria will be excluded.

1. Age less than 18 years
2. Acute ipsilateral proximal DVT episode within the last 3 months, or acute contralateral DVT for which thrombolytic therapy is planned
3. Lack of suitable inflow into the ipsilateral common femoral vein per the treating physician
4. Previous stent placement in the infrarenal IVC or ipsilateral iliac or common femoral vein
5. Absence of PTS of at least moderate severity
6. Chronic arterial limb ischemia (ankle-brachial index \< 0.5 within the previous 1 month) in the ipsilateral leg (if peripheral arterial disease is present or suspected, an ankle-brachial index should be obtained and documented)
7. Presence of open venous ulcer \> 50 cm2 area, suspicion for active ulcer infection, or visualization of bone or tendon within the ulcer in the ipsilateral leg
8. Inability to tolerate endovascular procedure due to acute illness, or general health
9. Severe allergy to iodinated contrast refractory to steroid premedication
10. Known allergy to stent or catheter components
11. Hemoglobin \< 8.0 g/dl, uncorrectable INR \> 3.05, or platelet count \< 75,000/ml
12. Severe renal impairment (on chronic dialysis or estimated GFR \< 30 ml/min)
13. Disseminated intravascular coagulation or other major bleeding diathesis
14. Pregnancy (positive pregnancy test)
15. Life-expectancy \< 6 months or chronically non-ambulatory for reasons other than PTS
16. Inability to provide informed consent or to comply with study assessments

Note - patients who initially meet an exclusion criterion can have eligibility re-evaluated on a subsequent occasion.