Aspirin and Clopidogrel Reactivity in Patients With Critical Limb Ischemia (CLI)

Prevalence of High On-Treatment (Aspirin and Clopidogrel) Platelet Reactivity in Patients With Critical Limb Ischemia

Critical Limb Ischemia (CLI) is defined as limb pain that occurs at rest, or impending limb loss that is caused by severe compromise of blood flow to the affected extremity. CLI is a major cause of death and disability (secondary to myocardial infarction, stroke and amputation). The mortality in patients with CLI approaches 25% and 50% at one and five years respectively. High on-treatment platelet reactivity (HPR) in patients treated with aspirin and clopidogrel (previously referred to as "resistance") is associated with an increased risk of recurrent cardiovascular events after percutaneous coronary interventions and acute coronary syndromes. The prevalence and significance of High on-treatment Platelet Reactivity (HPR) in patients with critical limb ischemia treated with aspirin and/or clopidogrel is not known.

The investigators project aims to investigate the prevalence of HPR (to aspirin and clopidogrel) in one hundred patients with diagnosis of critical limb ischemia encountered at University of Southern California (USC) affiliated hospitals (Los Angeles County Hospital and Keck Hospital of University of Southern California).

Study Overview

• Status: Completed
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Other: Blood draw only

Detailed Description

This prospective clinical study will investigate the prevalence of high on- treatment platelet reactivity (HPR) in one hundred patients with critical limb ischemia (CLI), at the Keck Hospital of USC and Los Angeles County Medical Center (LAC+USC). Platelet inhibition to aspirin will be evaluated with the VerifyNow® aspirin (ASA) test. Clopidogrel platelet inhibition will be evaluated with two different tests: the vasodilator-stimulated phosphoprotein (VASP) and the VerifyNow® purigenic receptor P2Y12 (VN-P2Y12) assays. All platelet function analyses will be performed once after a minimum of one week of uninterrupted dual antiplatelet therapy with aspirin and clopidogrel. High on-treatment Platelet Reactivity on aspirin treatment (HPRA) group will be defined as aspirin reaction units (ARU) ≥550 by the VerifyNow® ASA assay. High on-treatment Platelet Reactivity on clopidogrel (HPRC) group will be defined as P2Y12 reaction units (PRU) ≥208 by the VerifyNow® assay and Vasodilator-stimulated phosphoprotein-platelet reactivity index (VASP-PRI) ≥50% by the vasodilator-stimulated phosphoprotein (VASP) assay. All other patients will be assigned to the adequate platelet reactivity on therapy (APR) group. Prevalence of high on-treatment platelet reactivity will then be calculated for aspirin and/or clopidogrel

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The patient population will include one-hundred patients with a diagnosis of CLI. We will only include in the study CLI patients who as part of their standard of care medical treatment are receiving dual antiplatelet therapy with aspirin 81 mg and clopidogrel 75 mg daily for at least one week.

Description

Inclusion Criteria:

• EXPERIMENTAL GROUP: Patients with a diagnosis of critical limb ischemia (CLI) and uninterrupted treatment with aspirin and/or clopidogrel for at least one week before testing.
• CONTROL GROUP: 10 normal volunteers without any known co-morbidities

Exclusion Criteria:

• Chronic use of nonsteroidal anti-inflammatory drugs, thrombocytopenia (platelet count <100 × 103/μl), use of an oral anticoagulant (warfarin), glycoprotein (GP) IIb/IIIa inhibitors, or fibrinolytic drugs within 30 days before testing. Any documented history of hypercoaguable states or history of medication non-compliance.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Single cohort; Single cohort will receive Blood draw only.	Other: Blood draw only; Blood draw only

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Asses the Prevalence of High On-treatment Platelet Reactivity in Critical Limb Ischemia Patients Treated With Aspirin and Clopidogrel.	Platelet inhibition to aspirin will be evaluated with the VerifyNow® aspirin (ASA) test. Clopidogrel platelet inhibition will be evaluated with two different tests: the vasodilator-stimulated phosphoprotein (VASP) and the VerifyNow® purinergic receptor P2Y12 (VN-P2Y12) assays.	Single measurment after a minimum of one week of uninterrupted dual antiplatelet therapy with aspirin and clopidogrel

Collaborators and Investigators

• Sponsor: University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): June 19, 2013
• Primary Completion (Actual): November 21, 2016
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: March 19, 2014
• First Submitted That Met QC Criteria: March 21, 2014
• First Posted (Estimate): March 24, 2014

Study Record Updates

• Last Update Posted (Actual): June 28, 2019
• Last Update Submitted That Met QC Criteria: April 4, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: ASA-PLAVIX Reactivity in CLI
• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: D5130L00047/ISSBRIL0152

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO