Effect of VarIthena on Wound Healing in Venous Leg Ulcers (VLU)

This 12 month, multicenter, open-label registry is designed to collect treatment and outcome data related to participants treated with Varithena for great saphenous vein (GSV) system and/or anterior accessory saphenous vein (AASV) incompetence resulting in VLU. Participant are treated per Investigator's Standard of Care (SoC) and in accordance with the Full Prescribing Information (FPI) and Instructions for Use (IFU). For participants with healed ulcers during the 12 month follow-up period, VLU recurrence information is collected.

• Varithena (Drug): Administration procedures and volume are per standard of care, full prescribing information, and instructions for use.

Primary outcomes

• Change From Baseline in Wound Perimeter [Baseline to 12 weeks and to 12 months]: Mean change in wound perimeter as measured by photograph inputted into wound measuring technology platform. Larger number indicates a lower wound perimeter compared to baseline. Epithelial migration measured by change in perimeter of wound.
• Number of Wound Closure at 12 Weeks [Baseline to 12 weeks]: Total number of healed wounds at 12 weeks post treatment. Wound healing is measured measured by photograph inputted into wound measuring technology platform.
• Time to Wound Closure [Baseline to wound closure or to 12 months, whichever occurs first]: Median number of days to wound closure measured weekly. Wound closure as measured by photograph inputted into wound measuring technology platform.

Secondary outcomes

• Change in Pain [Baseline to 12 weeks and to 12 months]: Mean change in pain on numeric pain rating scale (NPRS) compared to baseline at 12 months post-treatment. Minimum value is "0" and maximum value is "10". Higher scores mean a worse outcome.
• Change on EQ-5D-5L Quality of Life Assessment [Baseline to 12 weeks and to 12 months]: Mean change on 5-level EQ-5D (EQ-5D-5L) quality of life assessment compared to baseline at 12 months post-treatment. Minimum value is "0" and maximum value is "1". Higher score mean better outcome.
• Change in VCSS [Baseline to 12 weeks and to 12 months]: Mean change in Venous Clinical Severity Score (VCSS) from baseline to 12 month follow up. VCSS assesses nine common signs/symptoms of venous disease and each item is scored individually with a minimum score of "0" and maximum score of "3". The individual items are added together to assess change from baseline. Higher scores mean worst outcome.
• Number of Wounds Remaining Closed at 3 Months Post-wound Closure Date [Baseline to 12 months]: Count of wounds remaining closed at 3 months post-wound closure determined via photograph and assessed by wound measurement technology platform.
• Number of Wound Recurrences [Baseline to 12 months]: Count of wound recurrences of healed wounds. For healed wounds, VLU recurrence was collected via phone calls and subjects at follow up timelines.
• Number of Ulcer Free Days [Baseline to 12 months]: Mean number of ulcer free days defined as days from baseline to date of recurrence

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Men and women; age ≥18
* Investigator has selected Varithena® to treat participants classified C6 with chronic (≥3 months) VLU resulting from GSV and/or AASV incompetence
* Wound can be visualized in one plane to allow for image collection of the entire wound in one photograph, or if wound is circumferential, participant must be able to capture the entire wound using multiple photographs taken from directly above the wound (straight on)
* Reflux >500 milliseconds (ms) on duplex ultrasound
* Willing and able to collect wound photographs and data using an application installed on a tablet
* Willing and able to return for scheduled follow-up and wound care visits
* Ability to comprehend and sign informed consent form (ICF) and complete questionnaires

Exclusion Criteria:

* Contraindications to Varithena® 1% in accordance with the FPI
* Any serious concomitant disease, per physician's discretion, that confounds wound healing, including malignant changes of wound
* Concomitant heat ablation, or heat ablation of index leg within 6 weeks prior to treatment with Varithena®
* Significant arterial disease or ankle-brachial pressure index (ABPI) ≤0.8
* In the opinion of Investigator, wound would close within 12 weeks without additional treatment

Participant flow

Outcome results

• Change From Baseline in Wound Perimeter (Primary), Mean, mm: Prospective Registry Cohort 29.36 +/- 146.13
• Number of Wound Closure at 12 Weeks (Primary), Number, wounds: Prospective Registry Cohort 43
• Time to Wound Closure (Primary), Median, days: Prospective Registry Cohort 89 (62 to 117)
• Change in Pain (Secondary), Mean, score on a scale: Prospective Registry Cohort -1.4 +/- 3.1
• Change on EQ-5D-5L Quality of Life Assessment (Secondary), Mean, score on a scale: Prospective Registry Cohort 0.066 +/- 0.233
• Change in VCSS (Secondary), Mean, score on a scale: Prospective Registry Cohort -5.8 +/- 5.6
• Number of Wounds Remaining Closed at 3 Months Post-wound Closure Date (Secondary), Count of units, wounds: Prospective Registry Cohort 47
• Number of Wound Recurrences (Secondary), Number, wounds: Prospective Registry Cohort 7 (5.4 to 24.9)
• Number of Ulcer Free Days (Secondary), Mean, days: Prospective Registry Cohort 240.5 +/- 118.9

Adverse events

Time frame: Adverse events were collected during a 1 year period starting from the initiation of treatment until the subject completes the registry follow up period or withdraws.

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2017-08-14)
• Statistical Analysis Plan (PDF, 2020-11-12)

• Michael Shao, MD, Principal investigator, Swedish Covenant Hospital