Great Saphenous Vein (GSV) With Venous Reflux Disease
Conditions
Keywords
GSV
Brief summary
The VeClose pivotal study was a controlled, randomized, prospective, multicenter, pivotal study in which patients with venous reflux in the great saphenous vein (GSV) were treated with either the VenaSeal closure system (VenaSeal SCS) or radiofrequency ablation (RFA) therapy.
Detailed description
The purpose of the VeClose study was to demonstrate safety and effectiveness of the VenaSeal SCS as being both 1) non-inferior to RFA therapy in achieving anatomical closure of lower extremity superficial truncal veins in patients with venous reflux through endovascular transcatheter embolization with coaptation of the GSV at 3 months, and 2) superior in the reduction of intraprocedural and post procedural pain and symptoms as compared to treatment with RFA. The study was designed to demonstrate safety of the VenaSeal SCS by follow-up visits that evaluated, via duplex ultrasound and physical exam, the presence of deep vein thrombosis and/or pulmonary embolus.
Interventions
DEVICEVenaSeal SCS
Non-tumescent, non-thermal, non-sclerosant procedure that uses a proprietary medical adhesive delivered endovenously to close the vein.
Radiofrequency thermal ablation of the GSV using the Covidien ClosureFast system.
DEVICERoll-in (VenaSeal SCS)
Non-tumescent, non-thermal, non-sclerosant procedure that uses a proprietary medical adhesive delivered endovenously to close the vein.
Sponsors
Sapheon, Inc.
Medtronic Endovascular
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 21 years and ≤ 70 years of age at the time of screening 2. Reflux in the great saphenous vein (GSV) greater than 0.5 sec reflux 3. One or more of the following symptoms related to the target vein: aching, throbbing, heaviness, fatigue, pruritis, night cramps, restlessness, generalized pain or discomfort, swelling 4. GSV diameter while standing of 3-12 mm throughout the target vein as measured by Duplex ultrasound 5. Clinical, etiology, assessment and pathophysiology (CEAP) classification of C2 (if symptomatic) - C4b 6. Ability to walk unassisted 7. Ability to attend follow-up visits 8. Ability to understand the requirements of the study and to provide informed consent
Exclusion criteria
1. Life expectancy \< 1 year 2. Active treatment for malignancy other than non-melanoma skin cancer 3. Symptomatic peripheral arterial disease with ankle-brachial index (ABI) \<0.89 4. Daily use of narcotic or non-steroidal anti-inflammatory pain medications to control pain associated with GSV reflux 5. Current, regular use of systemic anticoagulation (e.g., warfarin, heparin) 6. Previous or suspected deep vein thrombosis (DVT) or pulmonary embolus (PE) 7. Previous superficial thrombophlebitis in GSV 8. Previous treatment of venous disease in target limb, other than spider vein treatment 9. Known hypercoagulable disorder 10. Conditions which prevent vein treatment with either RFA or VenaSeal SCS 11. Immobilization or inability to ambulate 12. Pregnant prior to enrollment 13. Tortuous GSV, which, in the opinion of the investigator, will limit catheter placement or require more than one primary access site 14. Aneurysm of the target vein with local diameter \>12 mm 15. Significant, incompetent, ipsilateral small saphenous, intersaphenous or anterior accessory great saphenous vein(s) 16. Known sensitivity to cyanoacrylate (CA) adhesives 17. Current participation in another clinical study involving an investigational agent or treatment, or within the 30 days prior to enrollment 18. Patients who require bilateral treatment during the next 3 months 19. Patients who require additional ipsilateral treatments on the same leg within 3 months following treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Closure of the Target Vein at 3 Months | 3 months | The primary endpoint of the study was complete closure of the target vein at 3 months after index treatment as judged by the vascular ultrasound laboratory. Complete closure was defined as Doppler ultrasound examination showing closure along the entire treated vein segment with no discrete segments of patency exceeding 5 cm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intraoperative Pain | During the operative procedure, which was an average of 24 minutes for VenaSeal SCS, 19 minutes for RFA, and 31 minutes for Roll-in group. | After the procedure, pain experienced during the procedure was rated by the subjects on a 0-10 numeric rating scale (NRS) where 0 represents no pain whatsoever and 10 represents worst imaginable pain. |
| Ecchymosis at Day 3 | First follow up visit at day 3 | At the Day 3 visit, the investigator visually rated the subject's ipsilateral leg for the occurrence of ecchymosis along the treated area based on a Scale for Ecchymosis Assessment with a 0-5 rating scale, with 0 being the best possible outcome and 5 being the worst possible outcome. The treatment area was defined as the area of skin overlying the treated vein, excluding the 5 cm of skin immediately adjacent to the access site. The rating scale was based on the percentage of ecchymosis of the treated area according to the following criteria: 0 rating = no ecchymosis, 1. rating = less than 25% ecchymosis, 2. rating = 25-50% ecchymosis, 3. rating = 50-75% ecchymosis, 4. rating = 75-100% ecchymosis, 5. rating = extension of ecchymosis above or below the treated area. |
Countries
United States
Participant flow
Recruitment details
The VeClose pivotal study was a prospective, multicenter, randomized, controlled study in which patients with venous reflux in the great saphenous vein (GSV) were treated with either VenaSeal SCS or radiofrequency ablation (RFA) therapy. Patients were treated between March 2013 and September 2013. There were 10 sites with 242 subjects.
Pre-assignment details
The VeClose study had two phases: a roll-in phase and a randomization phase. At each site, the first two enrolled subjects were treated with VenaSeal SCS only (no randomization) as roll-in cases. Following completion of the roll-in phase, the site entered the randomized phase where subjects were assigned to either VenaSeal SCS or RFA cohort.
Participants by arm
| Arm | Count |
|---|---|
| Roll-In (VenaSeal SCS) Endovenous delivery of VenaSeal Adhesive (VA) to a target site in diseased great saphenous veins (GSV). At each site, the first two enrolled subjects were treated with VenaSeal SCS only (no randomization). These subjects underwent the same preoperative and postoperative assessments (with the same schedule) as patients who underwent randomization. | 20 |
| VenaSeal SCS (Randomized Phase) Endovenous delivery of VenaSeal Adhesive (VA) to a target site in diseased great saphenous veins (GSV). Following completion of the Roll-in phase, subjects were then randomized at each site in a 1:1 fashion to either VenaSeal SCS or RFA. | 108 |
| RFA (Randomized Phase) Endovenous insertion of the ClosureFast radiofrequency ablation (RFA) catheter into a target site in diseased great saphenous veins (GSV). Following completion of the Roll-in phase, subjects were then randomized at each site in a 1:1 fashion to either VenaSeal SCS or RFA. | 114 |
| Total | 242 |
Baseline characteristics
| Characteristic | Roll-In (VenaSeal SCS) | VenaSeal SCS (Randomized Phase) | RFA (Randomized Phase) | Total |
|---|---|---|---|---|
| Age, Continuous | 53.1 years | 49.0 years | 50.5 years | 50.1 years |
| Sex: Female, Male Female | 17 Participants | 83 Participants | 93 Participants | 193 Participants |
| Sex: Female, Male Male | 3 Participants | 25 Participants | 21 Participants | 49 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 1 / 108 | 0 / 114 |
| other Total, other adverse events | 7 / 20 | 26 / 108 | 15 / 114 |
| serious Total, serious adverse events | 1 / 20 | 5 / 108 | 6 / 114 |
Outcome results
Primary
Number of Participants With Complete Closure of the Target Vein at 3 Months
The primary endpoint of the study was complete closure of the target vein at 3 months after index treatment as judged by the vascular ultrasound laboratory. Complete closure was defined as Doppler ultrasound examination showing closure along the entire treated vein segment with no discrete segments of patency exceeding 5 cm.
Time frame: 3 months
Population: Primary effectiveness was analyzed on the randomized cohort only and used an Intent to Treat (ITT) population, consisting of all treated subjects. The difference in success rates was calculated after imputing missing values with various methods.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| VenaSeal SCS (Randomized Phase) | Number of Participants With Complete Closure of the Target Vein at 3 Months | 107 Participants |
| RFA (Randomized Phase) | Number of Participants With Complete Closure of the Target Vein at 3 Months | 109 Participants |
Comparison: Last Observation Carried Forward (LOCF)p-value: <0.000195% CI: [-0.7, 7.6]One tailed Z-test
Secondary
Ecchymosis at Day 3
At the Day 3 visit, the investigator visually rated the subject's ipsilateral leg for the occurrence of ecchymosis along the treated area based on a Scale for Ecchymosis Assessment with a 0-5 rating scale, with 0 being the best possible outcome and 5 being the worst possible outcome. The treatment area was defined as the area of skin overlying the treated vein, excluding the 5 cm of skin immediately adjacent to the access site. The rating scale was based on the percentage of ecchymosis of the treated area according to the following criteria: 0 rating = no ecchymosis, 1. rating = less than 25% ecchymosis, 2. rating = 25-50% ecchymosis, 3. rating = 50-75% ecchymosis, 4. rating = 75-100% ecchymosis, 5. rating = extension of ecchymosis above or below the treated area.
Time frame: First follow up visit at day 3
Population: Completed Case (CC) analysis population consisted of all treated subjects for whom data were available for the endpoint.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VenaSeal SCS (Randomized Phase) | Ecchymosis at Day 3 | None | 15 Participants |
| VenaSeal SCS (Randomized Phase) | Ecchymosis at Day 3 | 25-50% | 0 Participants |
| VenaSeal SCS (Randomized Phase) | Ecchymosis at Day 3 | <25% | 5 Participants |
| VenaSeal SCS (Randomized Phase) | Ecchymosis at Day 3 | 75-100% | 0 Participants |
| VenaSeal SCS (Randomized Phase) | Ecchymosis at Day 3 | 50-75% | 0 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | None | 73 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | <25% | 29 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | 25-50% | 3 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | 50-75% | 2 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | 75-100% | 1 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | 75-100% | 1 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | 50-75% | 4 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | None | 55 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | 25-50% | 16 Participants |
| RFA (Randomized Phase) | Ecchymosis at Day 3 | <25% | 38 Participants |
Secondary
Intraoperative Pain
After the procedure, pain experienced during the procedure was rated by the subjects on a 0-10 numeric rating scale (NRS) where 0 represents no pain whatsoever and 10 represents worst imaginable pain.
Time frame: During the operative procedure, which was an average of 24 minutes for VenaSeal SCS, 19 minutes for RFA, and 31 minutes for Roll-in group.
Population: Completed Case (CC) analysis population consisted of all treated subjects for whom data were available for the endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VenaSeal SCS (Randomized Phase) | Intraoperative Pain | 1.28 scores on a scale | Standard Deviation 1.53 |
| RFA (Randomized Phase) | Intraoperative Pain | 2.16 scores on a scale | Standard Deviation 2.23 |
| RFA (Randomized Phase) | Intraoperative Pain | 2.35 scores on a scale | Standard Deviation 2.18 |