Intravascular Ultrasound-Guided Intervention for Venous Leg Ulcers (IGuideU)

Study Overview
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Brief Summary
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This clinical study is a global, prospective, multi-center, randomized controlled trial to determine if the use of intravascular ultrasound (IVUS) as an adjunctive imaging modality and as an interventional treatment guide will result in a more accurate diagnosis of deep vein occlusion (DVO), will guide optimal therapy, and will provide better clinical outcomes with reduced cost of care for patients presenting with persistent venous leg ulcers (VLUs).

Detailed Description
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This study will be conducted in 266 subjects presenting with venous ulcers that have previously undergone treatment for superficial of and/or perforator venous disease, if clinically indicated, followed by at least 3 months of prescribed compression therapy prior to screening. There are 6 study visits for each subject that will be completed over a period lasting approximately 24 months. Subjects will undergo a baseline/screening assessment (visit 1) followed by an interrogation procedure (visit 2) if the subject is enrolled into the interrogation arm. If the subject is randomized to the deferred interrogation arm, he/she will have a hospital/office visit in lieu of the interrogation procedure, which will be considered visit 2. For statistical purposes, the wound assessment performed at the index procedure/hospital visit will be considered the baseline measurement. 30±14 days and 90±14 days after Visit 2, the subject will return to the office for a 1- and 3-month follow-up visit, respectively. The subjects will return at 6- and 12-months post-index procedure/Visit 2 for follow-up assessments. The follow-up period for this study will be approximately 24 months, with a phone call only at 24-months post-index procedure/visit 2. The clinical study has a planned enrollment period of 36 months and a planned study duration period of 5.17 years

Official Title
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Intravascular Ultrasound-Guided Intervention for Venous Leg Ulcers

Conditions
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Venous Ulcer of Leg

Intervention / Treatment
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* Diagnostic Test: IVUS
* Other: Continued Compression Therapy/Stockings


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be between 18 and 85 years of age. Able and willing to participate and comply with the protocol, including the defined follow-up schedule, by signing an Institutional Review Board (IRB) or Ethics Committee approved informed consent form. Active venous leg ulcer (CEAP C6). Previously completed treatment for clinically significant reflux in the superficial and/or perforator venous system of the target limb at least 3 months prior to enrollment, if clinically indicated. Completed at least 3 months of prescribed compression therapy after any ablation. Palpable dorsalis pedis or posterior tibial artery (DP/PT) pulses at ipsilateral foot or ankle brachial index (ABI) ≥0.8. Be able to ambulate unassisted or with non-motorized assistive devices. Current VLU present ≤48 months. Exclusion Criteria: Patient is known pregnant or breast-feeding or planning to become pregnant in the following year. If antiplatelet and anticoagulation therapy cannot be tolerated. Previous venous stent implantation involving the target limb, target lesion, or inferior vena cava. Previous venovenous bypass surgery involving the target limb. Previous endovascular recanalization of the target lesion segment. Known metal allergy precluding stent implantation. Known or suspected to have inadequate inflow to support stent patency in the target limb. Active cancer diagnosis. Known positive test for COVID-19 (Sars-CoV-2) within the last 2 weeks and actively symptomatic. Known or suspected venous outflow obstruction caused by tumor compression/encasement with or without thrombus. Known allergy to contrast media that cannot adequately be pre-medicated prior to study procedure. Known renal dysfunction (defined as eGFR <30mL/min/1.73m2) that would preclude adequate contrast usage. Diagnosed with right heart failure/pulmonary hypertension. Has known clinically significant abnormal platelet count outside laboratory reference ranges. Has known clinically significant abnormal white blood cell count (WBC), fever, sepsis or positive blood culture. Organ transplant requiring immunosuppressant therapy. Unstable angina pectoris, or myocardial infarction within 30 days and/or hemorrhagic stroke within 3 months. Subjects with an active diagnosis of osteomyelitis of the ipsilateral limb. Previous or planned surgical or catheter-based procedure on index leg within 30 days before or 30 days after the index procedure. Active participation in another investigational drug or device study. Subject has any condition, which, in the opinion of the investigator, precludes the subject from participation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Interrogation Arm<br>patients will first be evaluated with MPV (limited to 3 views). The prescribed course of treatment based on the MPV results will be documented and patients will then be evaluated using IVUS. A treatment plan based on IVUS results will be compared with the MPV guided treatment plan and any differences will be documented. Any patients determined to still require venous stenting based on IVUS results will be stented accordingly using IVUS to guide stent placement. | Diagnostic Test: IVUS<br>* Those who are randomized to the interrogation arm will have diagnostic imaging performed by IVUS to determine their treatment plan.<br>|
| Other: Deferred Interrogation Arm<br>Deferred Interrogation Guidelines for this study are as follows: Mandate: • Continued compression therapy/stockings as prescribed. Allow: Periodic leg elevation. Sclerotherapy under ulcer bed. Recommend mechanical debridement as needed. Wound biopsy if evidence of infection. Systemic antibiotics if patient is diagnosed with an infection, avoid prophylactic prescription. Pain management medication (Pentoxifylline/Trental) allowed but not recommended Topical antimicrobial as needed. Prohibit: Negative pressure systems. Artificial and/or autologous skin grafting within first 3 months after randomization and within the first 3 months for subjects that crossover from deferred interrogation to the interrogation arm. | Other: Continued Compression Therapy/Stockings<br>* Those who are randomized to the deferred interrogation arm while continue compression therapy as prescribed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of detection and difference in complete ulcer healing between the interrogation group and the deferred interrogation group | Rate of detection and difference in complete ulcer healing between the interrogation group and the deferred interrogation group at 3 months. Complete ulcer healing is defined by 100% epithelialization of the venous ulcer. Healing will not be assumed for any area of the wound where a scab is present. | 3 Months | 
| Composite of the difference in deep venous obstruction (DVO) detection and the subsequent changes in treatment plan informed by IVUS compared to MPV. | Composite of the difference in DVO detection and the subsequent changes in treatment plan informed by IVUS compared to multiplanar venography (MPV). DVO is defined as ≥50% diameter reduction in the deep venous system as assessed by MPV or ≥50% reduction in cross-section area of the deep venous system assessed by IVUS. Changes in treatment plan will be assessed by use of a patient diary and follow up patient visits up to 24 months. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Ulcer healing measured | Rate of ulcer healing measured between groups at 3,6,12,18, and 24 months | 3,6,12,18, and 24 months | 
| Rate of Ulcer healing for stented patients | Rate of ulcer healing for stented post-thrombotic syndrome (PTS) and non-thrombotic iliac vein lesion (NIVL) patients at 3,6,12,18, and 24 months | 3,6,12,18, and 24 months | 
| Rate of recurring ulcers in both arms | Rate recurring ulcers in both arms from 3 months out to follow-up visit 24 months provided each arm has at least 30 subjects. The choice of 30 is based on central limit theorem in order to have normally distributed data for descriptive summary statistics. | 3-24 months | 
| Rate of recurring ulcers between post-thrombotic syndrome and non-thrombotic iliac vein lesion patients | Rate of recurring ulcers between PTS and NIVL sub-groups | up to 24 months | 
| Change in Quality of Life scores using the EQ5D-5L as compared in both arms | Change in QOL scores for both arms using the EQ5D-5L. The scale uses a scoring system of 0-100. Each response is assigned a number 1-5 and then added at the end to equal a number between 0-100. The higher the total, the better the score. | up to 24 months | 
| Change in Quality of Life scores using the 36 Item Short Form question assessment as compared in both arms | Change in QOL scores for both arms using the 36 Item Short Form question assessment. The responses are coded using a scoring key, then averaged to get a final score in each of the 8 categories utilized on the assessment. Items are scored ranging from 0-100. The higher the average, the better the score. | up to 24 months | 
| Change in clinical score using the Venous Ulcer Assessment (VCSS) | Change in clinical score will be assessed using the VCSS. The VCSS consists of 10 questions, each response is scored on a scale of 0-3. The total score ranges between 0-30 and is used to assess changes in disease severity over time. A lower score is a better outcome. | up to 24 months | 
| Change in clinical classification using the Clinical Etiology and Anatomy Pathology classification system | Change in clinical classification will be assessed using the Clinical Etiology and Anatomy Pathology (CEAP) scoring system. The system is designed to classify chronic venous disease. The clinical classification consists of 7 possibilities, ranging from 0-6, followed by sub categories to assign 1)symptoms, 2) etiologic classification, 3) anatomic classification, 4)pathophysiologic, and 5) anatomic segment classification. The lower the clinical classification score, the less severe the disease state. | up to 24 months | 
| Rate of medical resource utilization between the interrogation arm and deferred interrogation arms | Health economic analysis consisting of medical resource utilization (MRU) between the interrogation and deferred interrogation arms. A patient diary will be used to assess the rate of medical resource use (i.e. hospital, urgent care, office visits related to treatment of the study ulcer). | up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VLU, venous leg ulcer, ulcer, venous leg wound, venous stenting, IVUS, DVO