VANISH-2: Polidocanol Endovenous Microfoam (PEM) Versus Vehicle for the Treatment of Saphenofemoral Junction (SFJ) Incompetence
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: polidocanol injectable foam, 0.125%
|
Drug: polidocanol injectable foam, 0.125%
active placebo for blinding
|
Experimental: polidocanol injectable foam, 0.5%
|
Drug: polidocanol injectable foam, 0.5%
0.5% polidocanol foam injection
|
Experimental: polidocanol injectable foam, 1.0%
|
Drug: polidocanol injectable foam, 1.0%
1.0% polidocanol foam injection
|
Placebo Comparator: Vehicle
|
Drug: Vehicle
injection of vehicle comparator
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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).
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Dothan | Alabama | United States | 36303 | |
2 | San Diego | California | United States | 92120 | |
3 | San Diego | California | United States | 92121 | |
4 | Lafayette | Indiana | United States | 47905 | |
5 | Frederick | Maryland | United States | 21701 | |
6 | Hunt Valley | Maryland | United States | 21030 | |
7 | Los Alamos | New Mexico | United States | 87544 | |
8 | Oklahoma City | Oklahoma | United States | 73104 | |
9 | Monroeville | Pennsylvania | United States | 15143 | |
10 | Pittsburgh | Pennsylvania | United States | 15232 | |
11 | Greenville | South Carolina | United States | 29615 | |
12 | Bellevue | Washington | United States | 98004 |
Sponsors and Collaborators
- Boston Scientific Corporation
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- VAP.VV016
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Three (3) patients were randomized but never treated. |
Arm/Group Title | Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% |
---|---|---|---|---|
Arm/Group Description | Vehicle: Injection of vehicle comparator | active placebo for blinding of therapeutic polidocanol dose | lower experimental polidocanol dose | 1.0% polidocanol foam injection |
Period Title: Overall Study | ||||
STARTED | 59 | 58 | 60 | 58 |
Patients Receiving Blinded Treatment | 57 | 57 | 60 | 58 |
COMPLETED | 56 | 57 | 60 | 57 |
NOT COMPLETED | 3 | 1 | 0 | 1 |
Baseline Characteristics
Arm/Group Title | Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% | Total |
---|---|---|---|---|---|
Arm/Group Description | Vehicle: Injection of vehicle comparator | polidocanol injectable foam active placebo | polidocanol injectable foam lower experimental dose | polidocanol injectable foam therapeutic dose | Total of all reporting groups |
Overall Participants | 57 | 57 | 60 | 58 | 232 |
Age (years) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [years] |
49.8
(10.44)
|
52.8
(10.06)
|
50.4
(9.89)
|
50.4
(11.42)
|
50.8
(10.47)
|
Sex: Female, Male (Count of Participants) | |||||
Female |
42
73.7%
|
43
75.4%
|
40
66.7%
|
44
75.9%
|
169
72.8%
|
Male |
15
26.3%
|
14
24.6%
|
20
33.3%
|
14
24.1%
|
63
27.2%
|
Race/Ethnicity, Customized (participants) [Number] | |||||
White |
54
94.7%
|
53
93%
|
55
91.7%
|
53
91.4%
|
215
92.7%
|
Black |
2
3.5%
|
1
1.8%
|
3
5%
|
0
0%
|
6
2.6%
|
Asian |
0
0%
|
1
1.8%
|
0
0%
|
1
1.7%
|
2
0.9%
|
American Indian/Eskimo |
0
0%
|
0
0%
|
0
0%
|
1
1.7%
|
1
0.4%
|
Other |
1
1.8%
|
2
3.5%
|
2
3.3%
|
3
5.2%
|
8
3.4%
|
Weight (kilograms) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [kilograms] |
83.0
(20.22)
|
85.3
(16.41)
|
88.8
(22.66)
|
81.4
(20.22)
|
84.8
(20.11)
|
Height (centimeters) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [centimeters] |
169.7
(9.45)
|
168.6
(9.38)
|
169.6
(10.47)
|
169.1
(9.27)
|
169.3
(9.61)
|
Calculated BMI (kg/m^2) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [kg/m^2] |
28.8
(5.76)
|
30.1
(19.48)
|
30.7
(6.28)
|
28.4
(6.45)
|
29.5
(6.03)
|
Outcome Measures
Title | Change in Patient-Reported Symptoms of Varicose Veins (VVSymQ Score) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
Number of subjects with a baseline value (VVSymQ) and value at the 8 week visit. |
Arm/Group Title | Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% |
---|---|---|---|---|
Arm/Group Description | Vehicle: Injection of vehicle comparator | polidocanol injectable foam, 0.125%: active placebo for blinding | experimental dose polidocanol injectable foam, 0.5% | polidocanol injectable foam, 1.0%: Injection of mid-dose PEM |
Measure Participants | 54 | 54 | 60 | 57 |
Least Squares Mean (Standard Error) [units on a scale] |
-2.00
(0.474)
|
-5.34
(0.476)
|
-6.01
(0.454)
|
-5.06
(0.463)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 0.125% |
---|---|---|
Comments | Comparison of polidocanol treatment groups versus placebo (absolute change from baseline to week 8 in patient assessment of symptoms of varicose veins (VVSymQ) score. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -3.34 | |
Confidence Interval |
(2-Sided) 95% -4.63 to -2.04 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 0.5% |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -4.00 | |
Confidence Interval |
(2-Sided) 95% -5.26 to -2.74 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 1.0% |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -3.05 | |
Confidence Interval |
(2-Sided) 95% -4.33 to -1.77 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline to 8 Weeks in Appearance as Rated by Patient (PA-V3) |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
patients with a baseline and week 8 visit. |
Arm/Group Title | Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% |
---|---|---|---|---|
Arm/Group Description | Vehicle: Injection of vehicle comparator | polidocanol injectable foam, 0.125%: active placebo for blinding | experimental dose polidocanol injectable foam, 0.5% | polidocanol injectable foam, experimental dose 1.0% |
Measure Participants | 56 | 56 | 60 | 57 |
Mean (Standard Error) [units on a scale] |
-0.07
(0.080)
|
-0.74
(0.081)
|
-0.89
(0.078)
|
-0.83
(0.080)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 0.125% |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -0.66 | |
Confidence Interval |
(2-Sided) 95% -0.88 to -0.45 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.081 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 0.5% |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -0.82 | |
Confidence Interval |
(2-Sided) 95% -1.04 to -0.61 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.078 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 1.0% |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -0.75 | |
Confidence Interval |
(2-Sided) 95% -0.97 to -0.54 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Change From Baseline at 8 Weeks Post-Treatment in IPR-V3 Score--Physician Photographic Review of Appearance |
---|---|
Description | 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 |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% |
---|---|---|---|---|
Arm/Group Description | Vehicle: Injection of vehicle comparator | polidocanol injectable foam, 0.125%: active placebo for blinding | experimental dose polidocanol injectable foam, 0.5% | polidocanol injectable foam, 1.0% experimental dose |
Measure Participants | 56 | 57 | 60 | 57 |
Least Squares Mean (Standard Error) [units on a scale] |
-0.32
(0.133)
|
-1.55
(0.131)
|
-1.86
(0.129)
|
-1.79
(0.130)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 0.125% |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -1.23 | |
Confidence Interval |
(2-Sided) 95% -1.59 to -0.87 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.131 |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 0.5% |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -1.54 | |
Confidence Interval |
(2-Sided) 95% -1.90 to -1.18 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.129 |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Vehicle, Polidocanol Injectable Foam, 1.0% |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.0001 |
Comments | ||
Method | ANCOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | Mean Difference (Final Values) |
Estimated Value | -1.47 | |
Confidence Interval |
(2-Sided) 95% -1.83 to -1.11 |
|
Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.130 |
|
Estimation Comments |
Adverse Events
Time Frame | Adverse events that occurred after patient provided informed consent through Visit 5/Week 8 (or Visit 8 for patients receiving open-label PEM 1.0%) | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||
Arm/Group Title | Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% | ||||
Arm/Group Description | Vehicle: Injection of vehicle comparator | polidocanol injectable foam, 0.125% active placebo | polidocanol injectable foam, 0.5% lower experimental dose | polidocanol injectable foam target therapeutic dose | ||||
All Cause Mortality |
||||||||
Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/59 (0%) | 0/58 (0%) | 0/60 (0%) | 0/58 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
Vehicle | Polidocanol Injectable Foam, 0.125% | Polidocanol Injectable Foam, 0.5% | Polidocanol Injectable Foam, 1.0% | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 11/59 (18.6%) | 24/58 (41.4%) | 27/60 (45%) | 47/58 (81%) | ||||
General disorders | ||||||||
Infusion site thrombosis | 0/59 (0%) | 0 | 6/58 (10.3%) | 6 | 7/60 (11.7%) | 7 | 16/58 (27.6%) | 16 |
Tenderness | 0/59 (0%) | 0 | 0/58 (0%) | 0 | 1/60 (1.7%) | 1 | 4/58 (6.9%) | 4 |
Musculoskeletal and connective tissue disorders | ||||||||
Pain in extremity | 7/59 (11.9%) | 7 | 9/58 (15.5%) | 9 | 4/60 (6.7%) | 4 | 10/58 (17.2%) | 10 |
Limb discomfort | 2/59 (3.4%) | 2 | 1/58 (1.7%) | 1 | 2/60 (3.3%) | 2 | 3/58 (5.2%) | 3 |
Back pain | 3/59 (5.1%) | 3 | 0/58 (0%) | 0 | 0/60 (0%) | 0 | 1/58 (1.7%) | 1 |
Vascular disorders | ||||||||
Thrombophlebitis superficial | 1/59 (1.7%) | 1 | 4/58 (6.9%) | 4 | 8/60 (13.3%) | 8 | 2/58 (3.4%) | 2 |
Venous thrombosis limb | 0/59 (0%) | 0 | 2/58 (3.4%) | 2 | 2/60 (3.3%) | 2 | 4/58 (6.9%) | 4 |
Hematoma | 1/59 (1.7%) | 1 | 2/58 (3.4%) | 2 | 3/60 (5%) | 3 | 3/58 (5.2%) | 3 |
Deep vein thrombosis | 0/59 (0%) | 0 | 0/58 (0%) | 0 | 0/60 (0%) | 0 | 5/58 (8.6%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | David Wright MBBS |
---|---|
Organization | BTG International Inc. |
Phone | 610-278-1660 |
david.wright@btgplc.com |
- VAP.VV016