Clinical trial NCT02660866: Excellence In Peripheral Artery Disease Thrombin Receptor Antagonist Intervention In Claudication Evaluation (XLPAD-TRACE Trial)
Official title: Excellence In Peripheral Artery Disease Thrombin Receptor Antagonist Intervention In Claudication Evaluation (XLPAD-TRACE Trial)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Peripheral Arterial Disease
Keywords: intermittent claudication
randomized controlled trial
Lead sponsor: North Texas Veterans Healthcare System
Sponsor class: FED
First posted: 2016-01-21
Enrollment: 200
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 4, randomized clinical trial to evaluate whether addition of Vorapaxar 2.08 mg daily vs. placebo daily on background antiplatelet therapy, prescribed for 6 months to patients with established peripheral artery disease (PAD) and Intermittent Claudication (IC) treated with standard medical therapy (SMT) would lead to an improvement in the peak walking time (PWT).

Detailed description: Primary trial objective: To evaluate whether addition of Vorapaxar 2.08 mg daily vs. placebo daily on background antiplatelet therapy, prescribed for 6 months to patients with established PAD and IC treated with standard medical therapy (SMT) would lead to an improvement in the peak walking time (PWT)

Study endpoints Primary endpoint: Change from baseline to 6 months in the PWT on a graded treadmill test (GTT per Gardner protocol) between participants enrolled in the test and control arms of the study

Secondary endpoints

* Change from baseline to 6 months in the claudication onset time (COT) on GTT between participants enrolled in the test and control arms of the study.
* Change from baseline to 6 months in the walking impairment questionnaire distance scores (WIQ) between participants enrolled in the test and control arms of the study.
* Change from baseline to 6 months in self-reported quality of life score using the Medical Outcomes Study 12-Item Short form survey (SF-12) between participants enrolled in the test and control arms of the study

Tertiary endpoints

* The first occurrence of clinically indicated lower extremity endovascular or surgical revascularization procedure during the entire study duration post-randomization in participants enrolled in the test or control arms of the study.
* The first occurrence of all-cause death, MI, ischemic stroke during the entire study duration post-randomization in participants enrolled in the test or control arms of the study.
* The first occurrence of severe bleeding defined according to the Global Utilization of Streptokinase and Tissue plasminogen activator for Occluded coronary arteries (GUSTO) classification during the entire study duration post-randomization in participants enrolled in the test or control arms of the study.

Eligibility criteria: Pre-screening criteria

* Laboratory values available ≤ 1 year of the date of screening: hemoglobin ≥9g, platelet count \>50,000 mm3 or \<600,000 mm3
* No history of stroke or transient ischemic attack (TIA)
* No allergy to aspirin
* ≥40 years of age
* Presence of documented PAD by ABI \<0.80 at rest or ≥20% drop in claudication limited exercise ABI in any limb and one of the following criteria in the corresponding limb:

  i.Prior surgical and/or endovascular lower extremity intervention (infra-renal aorta to pedal arteries) ii. Known presence of flow-limiting stenosis (≥70%) by clinically indicated angiography, computed tomographic (CT) or magnetic resonance imaging (MRI) tests or by Duplex ultrasonography (DUS) defined standard clinical criteria in lower extremity arteries
* Documented IC Rutherford/Becker (RC) category ≥2
* Presence of any one of the listed classes of agents \[angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), lipid lowering therapy, aspirin and beta-blocker drugs\]-No MI or percutaneous coronary intervention (PCI) with DES within the past 11 months
* No planned surgical or endovascular procedures other than for the treatment of IC for the expected duration of the study
* No warfarin or other chronic oral anticoagulant use within the last 14 days
* No use of ticagrelor, clopidogrel, prasugrel or ticlopidine within last 7 days
* No contraindication(s) to the use of antithrombin or antiplatelet agents (history of intra-cerebral hemorrhage or ICH, presence of intracerebral mass, recent or \<12 weeks gastrointestinal bleed requiring blood transfusion, any blood transfusion within the last 6 weeks, any trauma requiring surgery within the last 4 weeks or any surgical or endovascular procedure within the last 4 weeks
* No use of cilostazol and/or pentoxyphilline within last 7 days
* Severe psychiatric or behavioral illness that in the judgement of the investigator precludes study participation
* No history of major or minor amputation
* Severe heart, vascular and lung disease in the discretion of the investigator that precludes study participation.
* Ability to walk for at least 15 min/day, at least 3 days/week, at ≥20 steps/min

Inclusion criteria

* Treadmill PWT= 2-10 min on Gardner protocol
* Estimated survival ≥1 year in the judgment of the site investigator
* Use of at least one aspirin dose within at least 5 days prior to randomization at 325 mg dose in aspirin naïve patients (0-5 days of prior aspirin use) or at least one aspirin dose prior to randomization at 81 mg dose in patients on chronic (\>5 days) aspirin therapy (at clinically indicated doses).
* Presence of any one of the listed classes of agents \[angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), lipid lowering therapy, aspirin and beta-blocker drugs\]

Exclusion Criteria:

* MI or percutaneous coronary intervention (PCI) with DES within the past 11 months
* Positive pregnancy test
* Planned surgical or endovascular procedures other than for the treatment of IC
* Warfarin or other chronic oral anticoagulant use within 14 days
* Use of Ticagrelor, Clopidogrel, Prasugrel or Ticlopidine within 7 days
* Contraindication(s) to the use of antithrombin or antiplatelet agents (history of intra-cerebral hemorrhage or ICH, presence of intracerebral mass, recent or \<12 weeks gastrointestinal bleed requiring blood transfusion, any blood transfusion within the last 6 weeks, any trauma requiring surgery within the last 4 weeks or any surgical or endovascular procedure within the last 4 weeks
* Use of cilostazol and/or pentoxyphilline within 7 days

Primary outcomes:
measure: Change from baseline to 6 months in the PWT on a graded treadmill test (GTT per Gardner protocol) between participants enrolled in the test and control arms of the study
timeFrame: 6 months
Secondary outcomes:
measure: Change from baseline to 6 months in the claudication onset time (COT) on GTT between participants enrolled in the test and control arms of the study.
timeFrame: 6 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System
state: Arizona
city: San Diego
country: United States
facility: San Diego VA Medical center
state: California
city: Denver
country: United States
facility: VA Eastern Colorado Healthcare System
state: Colorado
city: Atlanta
country: United States
facility: Atlanta Heart Specialists
state: Georgia
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis VA Medical center
state: Minnesota
city: Omaha
country: United States
facility: Creighton University
state: Nebraska
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Oklahoma City
country: United States
facility: OKlahoma VA Medical Center
state: Oklahoma
city: Portland
country: United States
facility: VA Portland Health Care System
state: Oregon
city: Dallas
country: United States
facility: VA North Texas Health Care System
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
Study officials:
References:
citation: Hirsch AT, Hiatt WR; PARTNERS Steering Committee. PAD awareness, risk, and treatment: new resources for survival--the USA PARTNERS program. Vasc Med. 2001;6(3 Suppl):9-12. doi: 10.1177/1358836X0100600i103.
citation: McBurney CR, Eagle KA, Kline-Rogers EM, Cooper JV, Mani OC, Smith DE, Erickson SR. Health-related quality of life in patients 7 months after a myocardial infarction: factors affecting the Short Form-12. Pharmacotherapy. 2002 Dec;22(12):1616-22. doi: 10.1592/phco.22.17.1616.34121.
citation: Tsai S, Liu Y, Alaiti MA, Gutierrez JA, Brilakis ES, Banerjee S. No benefit of vorapaxar on walking performance in patients with intermittent claudication. Vasc Med. 2022 Feb;27(1):33-38. doi: 10.1177/1358863X211042082. Epub 2021 Oct 5.