Intravascular Ultrasound for Peripheral Artery Disease Revascularization (CLARITY)

Intravascular Ultrasound for Peripheral Artery Disease Revascularization: The CLARITY Randomized Controlled Trial

The purpose of this study is to determine if IVUS use, as compared to angiography alone, prevent major adverse limb events (MALE) or binary restenosis (a greater than 50% re-narrowing of the treated artery) in adult patients who have CLTI and are undergoing percutaneous revascularization.

Study Overview

• Status: Recruiting
• Conditions: Restenosis; Chronic Limb Threatening Ischemia; Peripheral Arterial Disease(PAD); Intravascular Ultrasound; Major Adverse Limb Events
• Intervention / Treatment: Procedure: IVUS-guided strategy

• Study Type: Interventional
• Enrollment (Estimated): 772
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: CLARITY Project Office; Phone Number: 905-521-2100; Email: CLARITY@phri.ca

Study Locations

• Canada
  • Hamilton, Canada
    • Recruiting
    • Hamilton General Hospital
    • Contact: Tara Adrinopoulos
    • Principal Investigator: John Harlock, Doctor
  • Toronto, Canada
    • Recruiting
    • Unity Health Toronto - St. Micheal's Hospital
    • Contact: Javier Fernandez
    • Principal Investigator: Graham McClure, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients presenting with lower extremity PAD manifesting as CLTI:

   a. CLTI is defined as ischemic rest foot pain, nonhealing wounds, or gangrene present for at least two weeks and that is attributable to objectively proven arterial occlusive disease, compatible with Rutherford class 4, 5 or 6, with the following supporting hemodynamic criteria1: i. For ischemic rest pain (Rutherford category 4): Ankle systolic pressure < 40mmHg, toe pressure < 30mmHg, or flat-line transtarsal pulse volume recording, OR ii. For tissue loss (Rutherford category 5, 6): Ankle systolic pressure < 60 mmHg, toe pressure of < 40mmHg, or flat-line transtarsal volume recording, AND

2. Scheduled to undergo percutaneous revascularization, AND
3. Informed consent
4. Imaging evidence of an obstructive or occluded lesion (> 70%) in the infraiguinal circulation (e.g. femoral, popliteal, or infrapopliteal circulation) using angiography, ultrasound, computed tomography, or magnetic resonance imaging.
5. An infrapopliteal lesion must be located in the proximal 2/3 of native infrapopliteal vessels, with a vessel diameter of > 2.5mm by investigator visual assessment.
6. The distal margin of the most distal target lesion must be located > 10 cm proximal to the proximal margin on the ankle mortise. The vessel segment distal to the most distal target lesion must be patent all the way to the ankle, with no obstructive lesion (>50% stenosis).

Exclusion Criteria:

1. The presence of anatomic or comorbid conditions or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the potential participant's ability to participate in the trial or to comply with the follow-up requirements.
2. The presence of any medical conditions precluding percutaneous revascularization
3. The subject has previously had or requires surgical revascularization involving the vessel containing the target lesion of the ipsilateral extremity.
4. The subject is bedridden or unable to walk (with assistance is acceptable).
5. Life expectancy < 12 months
6. Age < 18 years
7. Active vasculitis, Buerger's disease, or acute limb-threatening ischemia
8. Planned above-ankle amputation of the index limb within four weeks of the index procedure.
9. Obstructive supra-inguinal "inflow" (>70% stenosis) which is not planned to be treated during index procedure or within 30 days of the index procedure.
10. The subject has had any amputation to the ipsilateral extremity other than the toe or forefoot, or the subject has had a major amputation to the contralateral extremity < 1 year before the index procedure and is not independently walking.

11. Extensive tissue loss that is salvageable only with complex foot reconstruction or non-traditional trans metatarsal amputations.

    1. Osteomyelitis that extends proximal to the metatarsal heads
    2. Gangrene involving the plantar skin of the forefoot, midfoot or heel
    3. Deep ulcer or large shallow ulcer (> 3 cm) involving the plantar skin of the f forefoot, midfoot, or heel
    4. Full-thickness heel ulcer
    5. Any wound with calcaneal bone involvement
    6. Wounds that would require flap coverage or complex wound management for large soft tissue defect
    7. Full-thickness wounds on the dorsum of the foot with exposed tendon or bone.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intravascular Ultrasound - guided strategy; Percutaneous revascularization will be performed using intravascular ultrasound.	Procedure: IVUS-guided strategy; Percutaneous revascularization will be performed using intravascular ultrasound. The operators will follow instructions to modify arteries hardened by calcium and use IVUS to optimize the equipment (balloon and stents) used to unblock the artery.
No Intervention: Angiography - guided strategy; A standard-of-care percutaneous revascularization will be performed without using intravascular ultrasound.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-to-first occurrence of MALE	Defined as unplanned above ankle amputation of the index limb or clinically driven target lesion revascularization, or target-lesion binary restenosis, defined as > 50% stenosis on imaging throughout follow-up.	From date of randomization until the date of first unplanned above ankle amputation of the index limb, clinically driven target lesion revascularization or target-lesion binary restenosis, assessed up to a maximum of 5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The composite of all-cause mortality, MALE, or target-lesion binary restenosis		From date of randomization until the date of death, MALE, or target lesion binary restenosis, assessed up to a maximum of 5 years.
MALE		From date of randomization, assessed up to a maximum of 5 years.
All-cause mortality		From date of randomization, assessed up to a maximum of 5 years.
Unplanned above-ankle amputation of the index limb		From date of randomization, assessed up to a maximum of 5 years.
Clinically-driven target lesion revascularization		From date of randomization, assessed up to a maximum of 5 years.
Target lesion binary restenosis		From date of randomization, assessed up to a maximum of 5 years.
Unplanned minor amputation of the index limb		From date of randomization, assessed up to a maximum of 5 years.
Wound healing status of the index limb based on the Wound, Ischemia, Foot Infection (WIFI) scale throughout follow-up	The WIFI assessment refers to the Wound, Ischemia, and Foot Infection (WIFI) classification system. This system is used to standardize the measurement of wound healing, particularly in patients with peripheral artery disease (PAD). It is not a questionnaire but rather a classification method that helps in assessing the severity of wounds, the degree of ischemia (restricted blood supply), and the presence of foot infections. Wound, Ischemia and foot infection are all graded on a scale of 0-3, with higher grades indicating more severe conditions.	From date of randomization, assessed up to a maximum of 5 years.
Change in the Walking Impairment Questionnaire (WIQ) score throughout follow-up	The Walking Impairment Questionnaire (WIQ) is a tool designed to measure walking ability in patients with Peripheral Arterial Disease (PAD). It assesses the impact of PAD on walking distance, walking speed, and the ability to climb stairs. The WIQ is particularly useful for evaluating the severity of walking impairment and the effectiveness of interventions aimed at improving walking ability in these patients. The WIQ includes several categories, each scored on a scale from 0 to 100, with higher scores indicating better walking ability. Each category score is calculated based on the patient's self-reported ability to perform these activities. The scores are then used to provide an overall assessment of the patient's walking impairment.	From date of randomization, assessed up to a maximum of 5 years.
Change in the Vascular Quality of Life Questionnaire-6 (VascQol-6) score throughout follow-up	The VascuQoL-6 questionnaire is a health-related quality of life (QoL) assessment tool specifically designed for patients with peripheral arterial disease (PAD). It is used in clinical practice and vascular registries to evaluate the impact of PAD on patients' quality of life. Scale Determination The VasQol-6 consists of six questions, each scored on a scale from 1 to 4. The scores for each question are summed to generate a total Quality of Life score. A higher total score indicates a better health status. Score 1: Indicates the worst health status. Score 4: Indicates the best health status.	From date of randomization, assessed up to a maximum of 5 years.

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2025
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: May 2, 2025
• First Submitted That Met QC Criteria: May 16, 2025
• First Posted (Actual): May 18, 2025

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Ischemia; Pathological Conditions, Signs and Symptoms; Chronic Limb-Threatening Ischemia; Peripheral Arterial Disease
• Other Study ID Numbers: 5251

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No