Venous Insufficiency
Conditions
Brief summary
VICARES is a prospective randomized, controlled, multi-center, double blind study treating venous insufficiency associated with incompetent saphenous veins with 1% and 3% Sodium Tetradecyl Sulfate (STS) solution utilizing the ClariVein system.
Detailed description
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.
Interventions
DEVICEClariVein RES
ClariVein system
DRUGSodium Tetradecyl Sulfate 1% Injection
Sodium Tetradecyl Sulfate STS 1% Injection
DRUGSodium Tetradecyl Sulfate 3% Injection
Sodium Tetradecyl Sulfate 3% Injection
Sponsors
Vascular Insights, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ClariVein RES 1% Injection Sodium Tetradecyl Sulfate 1% Injection single administration
ClariVein RES: ClariVein system
Sodium Tetradecyl Sulfate 1% Injection: Sodium Tetradecyl Sulfate STS 1% Injection | 10 |
| ClariVein RES 3% Injection Sodium Tetradecyl Sulfate 3% Injection single administration
ClariVein RES: ClariVein system
Sodium Tetradecyl Sulfate 3% Injection: Sodium Tetradecyl Sulfate 3% Injection | 9 |
| Total | 19 |
Baseline characteristics
| Characteristic | Total | ClariVein RES 3% Injection | ClariVein RES 1% Injection |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 8 Participants | 8 Participants |
| Body Mass Index (BMI) | 26.3 kg/m2 STANDARD_DEVIATION 4.86 | 27.1 kg/m2 STANDARD_DEVIATION 5.35 | 25.6 kg/m2 STANDARD_DEVIATION 4.54 |
| Diameter of Vein Section to be Treated | 7.15 centimeters (cm) STANDARD_DEVIATION 5.369 | 9.08 centimeters (cm) STANDARD_DEVIATION 7.49 | 5.41 centimeters (cm) STANDARD_DEVIATION 0.845 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 8 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Length of Vein Section to be Treated | 36.3 centimeters (cm) STANDARD_DEVIATION 11.29 | 34.6 centimeters (cm) STANDARD_DEVIATION 15.27 | 37.8 centimeters (cm) STANDARD_DEVIATION 6.49 |
| Patient-Reported Symptoms 7-Day Symptom Questionnaire (Average Daily Total Symptom Score | 10.9 units on a scale STANDARD_DEVIATION 3.76 | 11.3 units on a scale STANDARD_DEVIATION 4.18 | 10.6 units on a scale STANDARD_DEVIATION 3.39 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 8 Participants | 7 Participants |
| Region of Enrollment United States | 19 Participants | 9 Participants | 10 Participants |
| Retrograde Flow | 19 Participants | 9 Participants | 10 Participants |
| Saphenous Vein Reflux | 19 Participants | 9 Participants | 10 Participants |
| Sex: Female, Male Female | 16 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 2 Participants |
| Ultrasound Parameters at Screening: Leg Assessed Left | 9 Participants | 6 Participants | 3 Participants |
| Ultrasound Parameters at Screening: Leg Assessed Right | 10 Participants | 3 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 9 |
| other Total, other adverse events | 1 / 10 | 3 / 9 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 |
Outcome results
Primary
Patient-Reported Symptoms 7-Day Symptom Questionnaire (Heaviness, Achiness, Swelling, Throbbing & Itching) to Evaluate Improvement in Subject Reported Symptoms.
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ClariVein RES 1% Injection | Patient-Reported Symptoms 7-Day Symptom Questionnaire (Heaviness, Achiness, Swelling, Throbbing & Itching) to Evaluate Improvement in Subject Reported Symptoms. | 7.2 units on a scale | Standard Deviation 3 |
| ClariVein RES 3% Injection | Patient-Reported Symptoms 7-Day Symptom Questionnaire (Heaviness, Achiness, Swelling, Throbbing & Itching) to Evaluate Improvement in Subject Reported Symptoms. | 6.2 units on a scale | Standard Deviation 1.87 |
Comparison: Continuous variables summarized using descriptive statistics, specifically the mean, median, standard deviation, minimum and maximum. Categorical variables summarized using frequencies and percentages. All statistical tests will be performed at the 0.05 significance level (p -value ≤ 0.050) unless otherwise indicated. For efficacy analyses, missing post-treatment data will be imputed using last observation carried forward (LOCF). Missing safety data will not be imputed.p-value: <0.00195% CI: [-6.2, -2.3]t-test, 2 sided
Comparison: All statistical tests will be performed at the 0.05 significance level (p -value ≤ 0.050) unless otherwise indicated.p-value: 0.01195% CI: [-5.8, -1]t-test, 2 sided
Comparison: All statistical tests will be performed at the 0.05 significance level (p -value ≤ 0.050) unless otherwise indicated.p-value: 0.0195% CI: [-8.7, -1.6]t-test, 2 sided
Comparison: All statistical tests will be performed at the 0.05 significance level (p -value ≤ 0.050) unless otherwise indicated.p-value: 0.53195% CI: [-3.7, 1.3]ANCOVA
Secondary
Elimination of Saphenous Vein Reflux
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
Time frame: 12 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Vein Closure : No | 5 Participants |
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Vein Competency : Missing | 0 Participants |
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Vein Competency : Yes | 2 Participants |
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Vein Competency: No open segments > 5cm | 5 Participants |
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Vein Closure : Missing | 0 Participants |
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Saphenous Vein Reflux: Non-Responder | 3 Participants |
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Vein Competency : No | 3 Participants |
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Saphenous Vein Reflux: Responder | 7 Participants |
| ClariVein RES 1% Injection | Elimination of Saphenous Vein Reflux | Vein Closure : Yes | 5 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Saphenous Vein Reflux: Responder | 9 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Vein Closure : Yes | 9 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Vein Closure : No | 0 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Vein Closure : Missing | 0 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Vein Competency : Yes | 0 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Vein Competency : No | 0 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Vein Competency : Missing | 0 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Vein Competency: No open segments > 5cm | 9 Participants |
| ClariVein RES 3% Injection | Elimination of Saphenous Vein Reflux | Saphenous Vein Reflux: Non-Responder | 0 Participants |
Comparison: The secondary efficacy endpoint, the elimination of saphenous vein reflux at Week 12 posttreatment, will be summarized for both treatments combined using the count and percentage, together with a 95% Wilson (score) confidence interval for the proportion.95% CI: [72.7, 99.9]
Comparison: For elimination of saphenous vein reflux at Week 12 posttreatment, the treatment difference for ClariVein RES 1% Injection versus ClariVein RES 3% Injection for the proportion was assessed by a chi-square test together with a 95% Wilson (score) confidence interval for the treatment difference.p-value: 195% CI: [-20.5, 42.8]Chi-squared