Effect of PEM Treatment of Superficial Axial and Tributary Vein Reflux on Improvement of Wound Healing in VLUs
Primary Purpose
Leg Ulcer, Veins, Varicose, Venous Ulcer
Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Polidocanol Endovenous Microfoam (PEM)
Sponsored by
About this trial
This is an interventional treatment trial for Leg Ulcer focused on measuring Varithena, Polidocanol Endovenous Microfoam
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years old
- Active VLU with a CEAP classification of C6
- Non-healing VLU ≥ 1 month but not greater than 24 months
- In the case of more than one ulcer, the largest ulcer (compliant with study criteria) will be chosen as the study ulcer and treated in the study. Other ulcerations, if present on the same leg must be at least 2cm apart from the study ulcer.
- Demonstrable GSV insufficiency (as per the Society for Vascular Surgery [SVS] and the American Venous Forum [AVF] Guidelines) via venous insufficiency study (VIS) (11)
- VLU considered non-healing (clinically defined as ≤70% wound improvement) after a 4-5 week run-in period with compression therapy
- Venous leg ulcer size ≥ 2cm2 within the great saphenous distribution and must be visualized in one plane to allow for image collection of the entire wound in one photo by the Silhouette device.
- The ulcer must extend through both the epidermis and dermis, with no exposed tendon or bone
- The ulcer must be located below the knee
- The ulcer bed must have some viable tissues with some granulation tissue
- Able to tolerate effective compression bandaging
- Patients able to walk independently with or without mobility aids
- Ability to comprehend and sign an informed consent document and complete study questionnaires in English
- Able and willing to attend all follow up visits
Exclusion Criteria:
- Age < 18 years old
- Small saphenous vein (SSV) distribution VLUs
- Patients who had previously received interventions for underlying venous disease or prior VLU treatments that would not be considered to be conservative, in the opinion of the principal investigator
- Exposed bone, tendon, or fascia
- Deep vein reflux unless clinically insignificant in comparison to superficial reflux
- Patients with leg ulceration etiology other than venous insufficiency
- Severe rheumatoid arthritis
- History of radiotherapy to the ulcer site
- Uncontrolled congestive heart failure (left or right sided heart failure)
- Receiving corticosteroids or immune suppressive therapy
- Active clinical infection of the ulcer site, however, patients may be entered into the study after successful treatment of infection
- History of collagen vascular disease
- History of known malnutrition (albumin <3.0 g/dL)
- History of known uncontrolled diabetes [hemoglobin A1c (HgbA1c) >8.0%]
- History of known arterial insufficiency [ankle-brachial index (ABI) <0.7, transcutaneous oxygen (tcpO2) <35 mmHg, or toe-brachial index (TBI) <0.4]
- Signs of cellulitis, osteomyelitis, or necrotic or avascular ulcer bed(s)
- Active sickle cell disease
- Patients diagnosed with DVT or phlebitis in the affected limb in the last 6 months, or with acute pulmonary embolism (PE) in the last 6 months (contraindication to PEM)
- Known allergic response to polidocanol or heparin, including history of heparin-induced thrombocytopenia, and/or multiple allergic reactions (contraindication to PEM)
- Chronic renal disease, if deemed by the principal investigator to be severe enough to interfere with wound healing
- Known active or recurrent cancer, or currently receiving chemotherapy or radiation therapy
- Poorly controlled asthma
- Pulmonary edema
- Major surgery, prolonged hospitalization, or pregnancy within 3 months of screening
- Minor surgery within 1 month of screening
- Current alcohol or drug (illicit or prescription) abuse
- Pregnant or lactating women
- History of stroke
- Unable to comply with the procedures described in the protocol
- Unable to comply with compression therapy recommendations
- Unable to give informed consent
- Non-English speaking
- Enrolled in a clinical evaluation for another investigational wound-care device or drug
Sites / Locations
- OhioHealth Riverside Methodist Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Compression plus PEM
Arm Description
Patients will receive 4-5 weeks of compression therapy, followed by treatment with 1% polidocanol endovenous microfoam (PEM) and 12 additional weeks of compression therapy. If the treating physician determines that the vein is not closed after a subjective assessment of vein patency via standard-of-care limited duplex imaging, patients will be re-treated with PEM on Day 4.
Outcomes
Primary Outcome Measures
Ulcer healing rate
We will determine the change in ulcer healing rate following PEM treatment. Ulcer healing rate will be measured as the relative weekly change in ulcer perimeter (cm) from baseline, until either until fully healed, or up to the final active study visit at 12 weeks (whichever is sooner). Pre-treatment healing rate will be measured as the relative change in ulcer perimeter (cm) from baseline per week over the 4-5 week run-in period.
Secondary Outcome Measures
Proportion of patients who successfully heal
We will determine the proportion of patients who successfully heal by 12 weeks. "Successful" healing will be defined as complete resolution of the ulcer (0 cm), with a lack of disruption of the epithelium at the ulcer site.
Proportion of patients who experience symptomatic pulmonary embolism and deep vein thrombosis (PE and DVT, respectively) and other drug-related adverse events (AEs)
We will determine the proportion of patients who experience symptomatic pulmonary embolism and deep vein thrombosis (PE and DVT, respectively) and other drug-related adverse events (AEs) at 12 weeks (or the last active study visit if healed prior to 12 weeks). The most commonly reported drug-related AEs (occurring in ≥3% of patients) include pain/discomfort in extremity, infusion site thrombosis (retained coagulum), injection site hematoma or pain, and superficial thrombophlebitis.
Full Information
NCT ID
NCT02988063
First Posted
December 6, 2016
Last Updated
September 14, 2017
Sponsor
OhioHealth
Collaborators
BTG International Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02988063
Brief Title
Effect of PEM Treatment of Superficial Axial and Tributary Vein Reflux on Improvement of Wound Healing in VLUs
Official Title
Effect of Polidocanol Endovenous Microfoam (PEM) Treatment of Superficial Axial and Tributary Vein Reflux on Improvement of Wound Healing in Venous Leg Ulcers (VLUs)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Poor enrollment
Study Start Date
April 10, 2017 (Actual)
Primary Completion Date
September 12, 2017 (Actual)
Study Completion Date
September 12, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
OhioHealth
Collaborators
BTG International Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study evaluates the addition of polidocanol endovenous microfoam (PEM) to compression therapy to determine effectiveness in improving the healing of venous leg ulcers (VLUs) in adults with severe venous disease of the great saphenous vein (GSV). All participants will receive treatment with Varithena and compression therapy.
The purpose of this study is to assess whether the use of PEM to correct superficial axial and varicose vein reflux is effective in improving healing of VLUs, over treatment with compression alone.
Detailed Description
Compression therapy and polidocanol endovenous microfoam (PEM) are both used for the treatment of venous leg ulcers (VLUs), but they do so by different mechanisms.
Compression therapy applied by a wound care professional has been demonstrated to improve healing rates in patients with existing VLUs and to reduce ulcer recurrence, and is used consistently by treating physicians. Compression therapy consists of hosiery, tubular bandages and bandage systems comprising two or more components, which provide graduated compression to the lower limb in order to improve venous return and to reduce edema.
Polidocanol endovenous microfoam (PEM) is an injectable foam medication that is used to treat symptoms of venous disease, including venous leg ulcers (VLUs). The medication ("polidocanol") is in the foam ("endovenous microfoam"). PEM is injected through a catheter or by direct injection into the malfunctioning vein. The foam fills and treats the desired section of the vein, thereby collapsing the diseased vein. When the malfunctioning vein collapses, the microfoam is deactivated and blood flow shifts to healthier veins nearby.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leg Ulcer, Veins, Varicose, Venous Ulcer, Reflux, Venous Reflux, Venous Leg Ulcer, Varicose Veins, Varicose Ulcer, Varicose Veins Leg
Keywords
Varithena, Polidocanol Endovenous Microfoam
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Compression plus PEM
Arm Type
Experimental
Arm Description
Patients will receive 4-5 weeks of compression therapy, followed by treatment with 1% polidocanol endovenous microfoam (PEM) and 12 additional weeks of compression therapy. If the treating physician determines that the vein is not closed after a subjective assessment of vein patency via standard-of-care limited duplex imaging, patients will be re-treated with PEM on Day 4.
Intervention Type
Drug
Intervention Name(s)
Polidocanol Endovenous Microfoam (PEM)
Other Intervention Name(s)
Varithena
Intervention Description
Polidocanol endovenous microfoam (PEM) is a sclerosing agent indicated for the treatment of incompetent great saphenous veins, accessory saphenous veins, and visible varicosities of the great saphenous vein system above and below the knee. PEM improves the symptoms of superficial venous incompetence and the appearance of visible varicosities.
Primary Outcome Measure Information:
Title
Ulcer healing rate
Description
We will determine the change in ulcer healing rate following PEM treatment. Ulcer healing rate will be measured as the relative weekly change in ulcer perimeter (cm) from baseline, until either until fully healed, or up to the final active study visit at 12 weeks (whichever is sooner). Pre-treatment healing rate will be measured as the relative change in ulcer perimeter (cm) from baseline per week over the 4-5 week run-in period.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Proportion of patients who successfully heal
Description
We will determine the proportion of patients who successfully heal by 12 weeks. "Successful" healing will be defined as complete resolution of the ulcer (0 cm), with a lack of disruption of the epithelium at the ulcer site.
Time Frame
12 weeks
Title
Proportion of patients who experience symptomatic pulmonary embolism and deep vein thrombosis (PE and DVT, respectively) and other drug-related adverse events (AEs)
Description
We will determine the proportion of patients who experience symptomatic pulmonary embolism and deep vein thrombosis (PE and DVT, respectively) and other drug-related adverse events (AEs) at 12 weeks (or the last active study visit if healed prior to 12 weeks). The most commonly reported drug-related AEs (occurring in ≥3% of patients) include pain/discomfort in extremity, infusion site thrombosis (retained coagulum), injection site hematoma or pain, and superficial thrombophlebitis.
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years old
Active VLU with a CEAP classification of C6
Non-healing VLU ≥ 1 month but not greater than 24 months
In the case of more than one ulcer, the largest ulcer (compliant with study criteria) will be chosen as the study ulcer and treated in the study. Other ulcerations, if present on the same leg must be at least 2cm apart from the study ulcer.
Demonstrable GSV insufficiency (as per the Society for Vascular Surgery [SVS] and the American Venous Forum [AVF] Guidelines) via venous insufficiency study (VIS) (11)
VLU considered non-healing (clinically defined as ≤70% wound improvement) after a 4-5 week run-in period with compression therapy
Venous leg ulcer size ≥ 2cm2 within the great saphenous distribution and must be visualized in one plane to allow for image collection of the entire wound in one photo by the Silhouette device.
The ulcer must extend through both the epidermis and dermis, with no exposed tendon or bone
The ulcer must be located below the knee
The ulcer bed must have some viable tissues with some granulation tissue
Able to tolerate effective compression bandaging
Patients able to walk independently with or without mobility aids
Ability to comprehend and sign an informed consent document and complete study questionnaires in English
Able and willing to attend all follow up visits
Exclusion Criteria:
Age < 18 years old
Small saphenous vein (SSV) distribution VLUs
Patients who had previously received interventions for underlying venous disease or prior VLU treatments that would not be considered to be conservative, in the opinion of the principal investigator
Exposed bone, tendon, or fascia
Deep vein reflux unless clinically insignificant in comparison to superficial reflux
Patients with leg ulceration etiology other than venous insufficiency
Severe rheumatoid arthritis
History of radiotherapy to the ulcer site
Uncontrolled congestive heart failure (left or right sided heart failure)
Receiving corticosteroids or immune suppressive therapy
Active clinical infection of the ulcer site, however, patients may be entered into the study after successful treatment of infection
History of collagen vascular disease
History of known malnutrition (albumin <3.0 g/dL)
History of known uncontrolled diabetes [hemoglobin A1c (HgbA1c) >8.0%]
History of known arterial insufficiency [ankle-brachial index (ABI) <0.7, transcutaneous oxygen (tcpO2) <35 mmHg, or toe-brachial index (TBI) <0.4]
Signs of cellulitis, osteomyelitis, or necrotic or avascular ulcer bed(s)
Active sickle cell disease
Patients diagnosed with DVT or phlebitis in the affected limb in the last 6 months, or with acute pulmonary embolism (PE) in the last 6 months (contraindication to PEM)
Known allergic response to polidocanol or heparin, including history of heparin-induced thrombocytopenia, and/or multiple allergic reactions (contraindication to PEM)
Chronic renal disease, if deemed by the principal investigator to be severe enough to interfere with wound healing
Known active or recurrent cancer, or currently receiving chemotherapy or radiation therapy
Poorly controlled asthma
Pulmonary edema
Major surgery, prolonged hospitalization, or pregnancy within 3 months of screening
Minor surgery within 1 month of screening
Current alcohol or drug (illicit or prescription) abuse
Pregnant or lactating women
History of stroke
Unable to comply with the procedures described in the protocol
Unable to comply with compression therapy recommendations
Unable to give informed consent
Non-English speaking
Enrolled in a clinical evaluation for another investigational wound-care device or drug
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raghu Kolluri, MD
Organizational Affiliation
OhioHealth
Official's Role
Principal Investigator
Facility Information:
Facility Name
OhioHealth Riverside Methodist Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43214
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Effect of PEM Treatment of Superficial Axial and Tributary Vein Reflux on Improvement of Wound Healing in VLUs
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