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

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.

374 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. Clinical Centers, and followed for 24
months. The study will take approximately 6 years to complete.

Inclusion Criteria:

1. Disabling (moderate-to-severe) PTS, defined by a) presence of chronic venous disease >
3 months duration in a leg with history of DVT; and b) either a Venous Clinical
Severity Score (VCSS) > 8 or a Villalta PTS Scale score > 10 or an open venous ulcer);
and

2. Ipsilateral iliac vein obstruction documented within 3 months prior to screening by
either:

1. Occlusion 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:

1. Age less than 18 years

2. 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. Documented obstruction (occlusion or > 50% diameter stenosis) of an IVC filter

5. Chronic arterial limb ischemia (ankle-brachial index < 0.5)

6. Presence of open venous ulcer > 50 cm2 area, or suspicion for active ulcer infection
in the ipsilateral leg

7. Inability to tolerate endovascular procedure due to acute illness, or general health

8. Severe allergy to iodinated contrast refractory to steroid premedication

9. Known allergy to stent or catheter components

10. Hemoglobin < 8.0 g/dl, uncorrectable INR > 3.5, or platelet count < 50,000/ml

11. Severe renal impairment (estimated GFR < 30 ml/min)

12. Disseminated intravascular coagulation or other major bleeding diathesis

13. Pregnancy (positive pregnancy test)

14. Life-expectancy < 6 months or chronically non-ambulatory for reasons other than PTS

15. Inability to provide informed consent or to comply with study assessments Note -
patients who initially meet an exclusion criterion can be re-screened at a later date,
and may be enrolled if all eligibility criteria are met at that time.