Excellence In Peripheral Artery Disease Thrombin Receptor Antagonist Intervention In Claudication Evaluation (XLPAD-TRACE Trial)

Peripheral Arterial Disease Clinical Trial

— XLPADTRACE  

Official title:

Excellence In Peripheral Artery Disease Thrombin Receptor Antagonist Intervention In Claudication Evaluation (XLPAD-TRACE Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02660866
• Other study ID #: xlpadtrace
• Status: Recruiting
• Phase: Phase 4
• Start date: July 2016
• Est. completion date: July 2019

Study information

• Verified date: May 2018
• Source: North Texas Veterans Healthcare System
• Contact: Ishita Tejani, BDS, MS, MSPH
• Phone: 214-857-3048
• Email: ishita.tejani[@]va.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 2019
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Peripheral Arterial Disease
• Peripheral Vascular Diseases

Intervention

Drug:
• Placebo + background APT + SMT
Placebo drug therapy combined with standard medical therapy combined with Antiplatelet therapy (Aspirin therapy)
• Vorapaxar 2.08 mg/d + background APT + SMT.
Vorapaxar 2.08 mg/d combined with standard medical therapy combined with Antiplatelet therapy (Aspirin therapy)

Locations

Country	Name	City	State
United States	Atlanta Heart Specialists	Atlanta	Georgia
United States	VA North Texas Health Care System	Dallas	Texas
United States	VA Eastern Colorado Healthcare System	Denver	Colorado
United States	Texas Tech University Health Science Center	Lubbock	Texas
United States	Northwell Health	Manhasset	New York
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	Minneapolis VA Medical center	Minneapolis	Minnesota
United States	OKlahoma VA Medical Center	Oklahoma City	Oklahoma
United States	Creighton University	Omaha	Nebraska
United States	VA Portland Health Care System	Portland	Oregon
United States	San Diego VA Medical center	San Diego	California
United States	Southern Arizona VA Health Care System	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
North Texas Veterans Healthcare System

Country where clinical trial is conducted

United States, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		6 months
Secondary	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.	6 months