Deep Vein Thrombosis, Post Thrombotic Syndrome, Venous Insufficiency, Venous Leg Ulcer, Venous Reflux, Venous Stasis
Conditions
Keywords
deep vein thrombosis, superficial venous reflux, blood clot, post thrombotic syndrome, iliac vein obstruction
Brief summary
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).
Detailed description
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.
Interventions
DEVICEStents
US-guided puncture of vein, fluoroscopic monitoring of catheter/guidewire manipulations, baseline venogram and intravascular ultrasound of CFV through infrarenal IVC. Iliac vein should be pre-dilated to at least 12 mm. Bare, self-expanding stents made of elgiloy or nitinol legally marketed in the US for any indication and that are at least 12 mm in diameter should be used to recanalize the entire diseased segment of vein. The use of devices \> 14 mm is highly recommended for the iliac vein and should be dilated to at least 14 mm, unless compelling patient factors dictate dilatation to a smaller diameter. Balloon angioplasty of inflow veins if needed to optimize inflow, per standard practice.
Sponsors
Washington University School of Medicine
Ontario Clinical Oncology Group (OCOG)
Massachusetts General Hospital
Saint Luke's Mid America Heart Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
PTS is assessed at the 6-month follow-up visit. The examiner must be a study-designated blinded clinician (MD, RN, APRN, or PA) who has completed study-specific PTS training to standardize across sites. PTS examiners must be blinded to participant treatment arm allocation. Subjects are reminded to not reveal to clinic staff which therapy they received (EVT or No-EVT). Subjects should be examined in the afternoon to allow the symptoms and signs of PTS to manifest. 1. The subject should be asked to rate the symptoms on the Villalta PTS scale for each leg, record his/her ratings, and complete the QOL questionnaires. 2. The subject's legs should be unclothed and he/she should be seated facing the blinded clinician examiner. Without access to the subject's rating of symptoms, the examiner assesses the clinical signs required for the Villalta and VCSS measures. 3. Leg ulcers are assessed and measured by appropriately qualified personnel who are unaware of treatment arm allocation.
Intervention model description
This is an NIH-funded, Phase III, multicenter, randomized, open-label, assessor-blinded, parallel two-arm, controlled clinical trial.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 consent 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 \> 3.0, 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PTS Severity | over 6 months follow-up | "Venous Clinical Severity Scale (VCSS) score, adjusted for baseline" |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Venous quality of life | 6 months | VEINES-QOL questionnaire |
| Gereric quality of life | 6 months | Short-Form-36 survey, physical component score |
| Estimated calf volume | 6 months | Measure calf length/diameter, formula for truncated cone |
| Presence of open ulcer | 6 months | Blinded clinic assessment |
| PTS severity (secondary) | 6 months | Villalta PTS Scale score |
| Major bleeding | 6 months | Overt, requiring \> 2 units pRBC or critical location |
| Recurrent venous thrombeombolism | 6 months | Objectively confirmed proximal DVT or PE |
| Death | 6 months | All-cause mortality |
| Valvular reflux | 6 months | Venous Segmental Disease Scale, reflux score |
| Venous obstruction | 6 months | Venous Segmental Disease Scale, obstruction score |
| PTS severity (remote) | 12 months | Patient-Reported Villalta |
| Death Death | 24 months | All-cause mortality |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSuresh Vedantham, M.D.
Clinical Coordinating Center at Washington University School of Medicine
Outcome results
None listed