Varicose Veins
Conditions
Keywords
varicose veins
Brief summary
Varicose veins are enlarged, noticeably bulging veins, which commonly occur in the legs and may cause discomfort. In this study, patients with varicose veins in the legs will be participating. The purpose of this research study is to evaluate the safety and effectiveness of three different concentrations of an investigational drug, Polidocanol Endovenous Microfoam (PEM) compared to vehicle (inactive solution) in treating the symptoms and appearance of varicose veins.
Interventions
DRUGVehicle
injection of vehicle comparator
DRUGpolidocanol injectable foam, 0.125%
active placebo for blinding
DRUGpolidocanol injectable foam, 0.5%
0.5% polidocanol foam injection
DRUGpolidocanol injectable foam, 1.0%
1.0% polidocanol foam injection
Sponsors
Boston Scientific Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Incompetence of SFJ associated with incompetence of the GSV or other major accessory vein * Ability to comprehend and sign an informed consent document and complete study questionnaires in English * Ability to record symptoms in accordance with the protocol * Symptomatic varicose veins * Visible varicose veins
Exclusion criteria
* Patients who only have telangiectatic or reticular veins (Clinical Finding C1, as assessed by CEAP Classification of Venous Disorders). * Leg obesity impairing the ability to access the vein to be treated and/or to apply post-procedure compression bandaging and stockings * Ultrasonographic or other evidence of current or previous deep vein thrombosis or occlusion * Deep vein reflux unless clinically insignificant in comparison to superficial reflux * Peripheral arterial disease precluding the wearing of post-procedure compression bandaging and stockings * Reduced mobility * Major surgery, prolonged hospitalization or pregnancy within 3 months of screening * Major co-existing disease (e.g. malignancy; pulmonary disease; renal or hepatic insufficiency; serious skin disease/condition that may compromise the ability of the patient to comply with the compression protocol, etc.) * Known allergic response to polidocanol or heparin, including history of heparin-induced thrombocytopenia, and/or multiple allergic reactions * Current alcohol or drug abuse * Pregnant or lactating women * Women of childbearing potential not using effective contraception * History of DVT, pulmonary embolism, or stroke
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score) | 8 weeks | The 9 varicose vein symptoms were to be assessed and graded on a 6-point (i.e., 0-5) duration scale and an 11-point (i.e., 0-10) intensity scale, and the patient's level activity for that day was to be assessed and graded on the 6-point (i.e., 0-5) duration scale. The 9 varicose vein symptoms assessed using the e-diary were derived from the first question of the modified Venous Insufficiency Epidemiologic and Economic Study-Quality of Life/Symptoms (VEINES-QOL/Sym) instrument. The VVSymQ is a subset of 5 VEINES QOL/Sym items that have been determined in earlier studies to be most important to patients. The daily VVSymQ score is the sum of the duration scores for these 5 symptoms (scores range from 0 to 25). At Visit 2/baseline, Week 8, scores were calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3) | 8 weeks | The Patient Self-assessment of Visible Varicose Veins (PA-V3) instrument is a 5-point scale used by patients to evaluate the appearance of their visible varicose veins. On this single-item paper questionnaire, the instructions included a diagram fo the medial view of a leg with the area between the ankle and the groin circled. The patient was instructed to choose 1 of 5 response options that best described the appearance of the visible varicose veins of the leg that was treated in the study. The patient was instructed not to consider the appearance of the leg outside the circled area or of any spider veins. Possible responses ranged from Not at all noticeable (a score of 0) to Extremely noticeable (a score of 4). |
| Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance | 8 weeks | The Independent Photography Review--Visible Varicose Veins (IPR-V3) instrument is a 5-point scale used to assess the appearance of a patient's visible varicose veins. At baseline and Week 8, standardized digital photographs were taken of the medial view of the patient's target leg, from groin to ankle. An independent photography review panel, consisting of 3 trained, blinded clinicians, evaluated the appearance of the patient's visible varicose veins using the IPR-V3 instrument's 5-point scale (0-4, where 0=none and 4=very severe visible varicose veins). |
Countries
United States
Participant flow
Pre-assignment details
Three (3) patients were randomized but never treated.
Participants by arm
| Arm | Count |
|---|---|
| Vehicle Vehicle: Injection of vehicle comparator | 57 |
| Polidocanol Injectable Foam, 0.125% polidocanol injectable foam active placebo | 57 |
| Polidocanol Injectable Foam, 0.5% polidocanol injectable foam lower experimental dose | 60 |
| Polidocanol Injectable Foam, 1.0% polidocanol injectable foam therapeutic dose | 58 |
| Total | 232 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Withdrew Consent | 1 | 0 | 0 | 0 |
| Overall Study | Withdrew consent prior to randomization | 2 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% | Total |
|---|---|---|---|---|---|
| Age, Continuous | 49.8 years STANDARD_DEVIATION 10.44 | 52.8 years STANDARD_DEVIATION 10.06 | 50.4 years STANDARD_DEVIATION 9.89 | 50.4 years STANDARD_DEVIATION 11.42 | 50.8 years STANDARD_DEVIATION 10.47 |
| Calculated BMI | 28.8 kg/m^2 STANDARD_DEVIATION 5.76 | 30.1 kg/m^2 STANDARD_DEVIATION 19.48 | 30.7 kg/m^2 STANDARD_DEVIATION 6.28 | 28.4 kg/m^2 STANDARD_DEVIATION 6.45 | 29.5 kg/m^2 STANDARD_DEVIATION 6.03 |
| Height | 169.7 centimeters STANDARD_DEVIATION 9.45 | 168.6 centimeters STANDARD_DEVIATION 9.38 | 169.6 centimeters STANDARD_DEVIATION 10.47 | 169.1 centimeters STANDARD_DEVIATION 9.27 | 169.3 centimeters STANDARD_DEVIATION 9.61 |
| Race/Ethnicity, Customized American Indian/Eskimo | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 0 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Black | 2 participants | 1 participants | 3 participants | 0 participants | 6 participants |
| Race/Ethnicity, Customized Other | 1 participants | 2 participants | 2 participants | 3 participants | 8 participants |
| Race/Ethnicity, Customized White | 54 participants | 53 participants | 55 participants | 53 participants | 215 participants |
| Sex: Female, Male Female | 42 Participants | 43 Participants | 40 Participants | 44 Participants | 169 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 20 Participants | 14 Participants | 63 Participants |
| Weight | 83.0 kilograms STANDARD_DEVIATION 20.22 | 85.3 kilograms STANDARD_DEVIATION 16.41 | 88.8 kilograms STANDARD_DEVIATION 22.66 | 81.4 kilograms STANDARD_DEVIATION 20.22 | 84.8 kilograms STANDARD_DEVIATION 20.11 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 59 | 24 / 58 | 27 / 60 | 47 / 58 |
| serious Total, serious adverse events | 0 / 59 | 0 / 58 | 0 / 60 | 0 / 58 |
Outcome results
Primary
Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score)
The 9 varicose vein symptoms were to be assessed and graded on a 6-point (i.e., 0-5) duration scale and an 11-point (i.e., 0-10) intensity scale, and the patient's level activity for that day was to be assessed and graded on the 6-point (i.e., 0-5) duration scale. The 9 varicose vein symptoms assessed using the e-diary were derived from the first question of the modified Venous Insufficiency Epidemiologic and Economic Study-Quality of Life/Symptoms (VEINES-QOL/Sym) instrument. The VVSymQ is a subset of 5 VEINES QOL/Sym items that have been determined in earlier studies to be most important to patients. The daily VVSymQ score is the sum of the duration scores for these 5 symptoms (scores range from 0 to 25). At Visit 2/baseline, Week 8, scores were calculated.
Time frame: 8 weeks
Population: Number of subjects with a baseline value (VVSymQ) and value at the 8 week visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score) | -2.00 units on a scale | Standard Error 0.474 |
| Polidocanol Injectable Foam, 0.125% | Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score) | -5.34 units on a scale | Standard Error 0.476 |
| Polidocanol Injectable Foam, 0.5% | Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score) | -6.01 units on a scale | Standard Error 0.454 |
| Polidocanol Injectable Foam, 1.0% | Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score) | -5.06 units on a scale | Standard Error 0.463 |
Comparison: Comparison of polidocanol treatment groups versus placebo (absolute change from baseline to week 8 in patient assessment of symptoms of varicose veins (VVSymQ) score.p-value: <0.000195% CI: [-4.63, -2.04]ANCOVA
p-value: <0.000195% CI: [-5.26, -2.74]ANCOVA
p-value: <0.000195% CI: [-4.33, -1.77]ANCOVA
Secondary
Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance
The Independent Photography Review--Visible Varicose Veins (IPR-V3) instrument is a 5-point scale used to assess the appearance of a patient's visible varicose veins. At baseline and Week 8, standardized digital photographs were taken of the medial view of the patient's target leg, from groin to ankle. An independent photography review panel, consisting of 3 trained, blinded clinicians, evaluated the appearance of the patient's visible varicose veins using the IPR-V3 instrument's 5-point scale (0-4, where 0=none and 4=very severe visible varicose veins).
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance | -0.32 units on a scale | Standard Error 0.133 |
| Polidocanol Injectable Foam, 0.125% | Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance | -1.55 units on a scale | Standard Error 0.131 |
| Polidocanol Injectable Foam, 0.5% | Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance | -1.86 units on a scale | Standard Error 0.129 |
| Polidocanol Injectable Foam, 1.0% | Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance | -1.79 units on a scale | Standard Error 0.13 |
p-value: <0.000195% CI: [-1.59, -0.87]ANCOVA
p-value: <0.000195% CI: [-1.9, -1.18]ANCOVA
p-value: <0.000195% CI: [-1.83, -1.11]ANCOVA
Secondary
Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3)
The Patient Self-assessment of Visible Varicose Veins (PA-V3) instrument is a 5-point scale used by patients to evaluate the appearance of their visible varicose veins. On this single-item paper questionnaire, the instructions included a diagram fo the medial view of a leg with the area between the ankle and the groin circled. The patient was instructed to choose 1 of 5 response options that best described the appearance of the visible varicose veins of the leg that was treated in the study. The patient was instructed not to consider the appearance of the leg outside the circled area or of any spider veins. Possible responses ranged from Not at all noticeable (a score of 0) to Extremely noticeable (a score of 4).
Time frame: 8 weeks
Population: patients with a baseline and week 8 visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vehicle | Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3) | -0.07 units on a scale | Standard Error 0.08 |
| Polidocanol Injectable Foam, 0.125% | Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3) | -0.74 units on a scale | Standard Error 0.081 |
| Polidocanol Injectable Foam, 0.5% | Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3) | -0.89 units on a scale | Standard Error 0.078 |
| Polidocanol Injectable Foam, 1.0% | Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3) | -0.83 units on a scale | Standard Error 0.08 |
p-value: <0.000195% CI: [-0.88, -0.45]ANCOVA
p-value: <0.000195% CI: [-1.04, -0.61]ANCOVA
p-value: <0.000195% CI: [-0.97, -0.54]ANCOVA