VANISH-2: Polidocanol Endovenous Microfoam (PEM) Versus Vehicle for the Treatment of Saphenofemoral Junction (SFJ) Incompetence

Sponsor
Boston Scientific Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT01231373
Collaborator
(none)
235
12
4
45
19.6
0.4

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
  • Drug: polidocanol injectable foam, 0.125%
  • Drug: polidocanol injectable foam, 0.5%
  • Drug: polidocanol injectable foam, 1.0%
  • Drug: Vehicle
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
235 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Varisolve Polidocanol Endovenous Microfoam (PEM) 0.5% and 1% Compared to Vehicle for the Treatment on Saphenofemoral Junction (SFJ) Incompetence "VANISH-2"
Study Start Date :
Nov 1, 2010
Actual Primary Completion Date :
Sep 1, 2011
Actual Study Completion Date :
Aug 1, 2014

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

  1. 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

  1. 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).

  2. 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

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts 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

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.
Responsible Party:
Boston Scientific Corporation
ClinicalTrials.gov Identifier:
NCT01231373
Other Study ID Numbers:
  • VAP.VV016
First Posted:
Nov 1, 2010
Last Update Posted:
Apr 21, 2021
Last Verified:
Apr 1, 2021
Keywords provided by Boston Scientific Corporation
Additional relevant MeSH terms:

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

1. Primary Outcome
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
2. Secondary Outcome
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
3. Secondary Outcome
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

[Not Specified]

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
Email david.wright@btgplc.com
Responsible Party:
Boston Scientific Corporation
ClinicalTrials.gov Identifier:
NCT01231373
Other Study ID Numbers:
  • VAP.VV016
First Posted:
Nov 1, 2010
Last Update Posted:
Apr 21, 2021
Last Verified:
Apr 1, 2021