A Study Evaluating ClariVein With a Sclerosing Agent for the Treatment of Venous Insufficiency

Approximately 50 subjects diagnosed with an incompetent saphenous vein will be randomized to either 1% STS or 3% STS solution delivered by the ClariVein system under ultrasound guidance.

Study duration for individual study patients, including follow-up visits, is anticipated to be approximately 16 weeks.

• ClariVein RES (Device): ClariVein system
• Sodium Tetradecyl Sulfate 1% Injection (Drug), also known as STS 1%: Sodium Tetradecyl Sulfate STS 1% Injection
• Sodium Tetradecyl Sulfate 3% Injection (Drug), also known as STS 3%: Sodium Tetradecyl Sulfate 3% Injection

Primary outcomes

• Patient-Reported Symptoms 7-Day Symptom Questionnaire (Heaviness, Achiness, Swelling, Throbbing & Itching) to Evaluate Improvement in Subject Reported Symptoms. [12 weeks]: The VEINES-QOL (VEnous INsufficiency Epidemiological and Economic Study Quality of Life) comprises 25 items that quantify disease effect on quality-of-life, \& a symptom questionnaire (VEINES-Sym) with 10 items that measure physical symptoms. A subset of the reported symptoms to Question 1 of the VEINES QOL/Sym is referred to as the 7-Day Symptom Questionnaire was used in this study. Subject response to each symptom was rated on a common 4-point response scale with lower scores representing better daily health outcomes (4=all day, 3=several times today, 2=once today, 1=not today). Weekly average score was calculated if at least 4 daily scores were present in the previous week. Daily total symptom score derived as sum of the responses across all symptoms (range = 5 to 20) Improvement in patient reported symptoms using the 7-Day Symptom Questionnaire (Heaviness, Achiness, Swelling, Throbbing \& Itching) at post-treatment Week 12 compared to Baseline is the primary endpoint of this study.

Secondary outcomes

• Elimination of Saphenous Vein Reflux [12 weeks]: Evaluated by way of duplex ultrasound and read by Core Lab. Elimination of saphenous vein reflux can be achieved when ultrasound images demonstrate vein closure (no discrete open segment of vein > 5cm in length within the treatment section of the selected saphenous vein), or vein competency (defined as absence of retrograde flow > 0.5 seconds within any open portions of the treatment section of the selected saphenous vein) as assessed by duplex ultrasound. Responder = subjects who satisfies criteria for elimination of saphenous vein reflux

Sex: All, ages: 18 Years to 80 Years, accepts healthy volunteers

Inclusion Criteria:

1. Adult patient with incompetent saphenous vein
2. Saphenous vein reflux > 500ms (0.5s), as measured by duplex ultrasound
3. One or more of patient reported symptoms related to the target vein: i.e., heaviness, achiness, swelling, throbbing or itching.
4. Candidate for endovenous procedure

Exclusion Criteria:

1. Arterial insufficiency demonstrated by a history of peripheral arterial disease (PAD) that would preclude the wearing of compression stockings
2. Absence of a palpable pulse at posterior tibial or dorsalis pedis and an Ankle-Brachial Index (ABI) <0.6
3. Multi-segmental axial deep venous reflux in at least two contiguous venous segments (e.g., femoral and popliteal) in the ipsilateral extremity
4. Previous surgical or endovenous procedure in the treatment section of the target vein
5. Previous superficial thrombophlebitis of the target saphenous vein with scarring in the treatment section
6. Pregnant or breastfeeding
7. Known sensitivity or allergic response to Sodium Tetradecyl Sulfate (STS)
8. Known high risk of thrombosis
9. Known history of deep vein thrombus (DVT) or pulmonary embolism (PE), known history of acute superficial vein thrombus, known hypercoagulable condition, post thrombotic syndrome
10. Known history of anaphylaxis or presence of multiple severe allergies

Participant flow

Outcome results

• Patient-Reported Symptoms 7-Day Symptom Questionnaire (Heaviness, Achiness, Swelling, Throbbing & Itching) to Evaluate Improvement in Subject Reported Symptoms. (Primary), Mean, units on a scale: ClariVein RES 1% Injection 7.2 +/- 3.00; ClariVein RES 3% Injection 6.2 +/- 1.87 (p <0.001)
• Elimination of Saphenous Vein Reflux (Secondary), Count of participants, Participants: ClariVein RES 1% Injection 5; ClariVein RES 3% Injection 9

Adverse events

Time frame: AE data collection began after ICF is signed and continued until completion of subject's Week 12 post-treatment follow-up visit (Visit 6). Any AE or SAE having an onset after the completion of Visit 6 (end of the study visit) was not collected or reported unless the Investigator determined event to be related to the study drug.

Other adverse events by term

Limitations and caveats: A total of 19 subjects were enrolled in the study. The study was terminated for administrative reasons; there were no safety or efficacy concerns. It was determined by the sponsor that the Phase 3 protocol, which is designed to closely mimic the Phase 2 protocol, would be adequate to collect safety and efficacy assessments with minor adjustments.

• Study Protocol and Statistical Analysis Plan (PDF, 2017-07-11)

• Mark H Meissner, MD, Study chair, Vascular and Endovascular Surgery Clinic at UWMC