Critical Limb Ischemia
Conditions
Keywords
ASA-PLAVIX Reactivity in CLI
Brief summary
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).
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
Interventions
OTHERBlood draw only
Blood draw only
Sponsors
University of Southern California
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Asses the Prevalence of High On-treatment Platelet Reactivity in Critical Limb Ischemia Patients Treated With Aspirin and Clopidogrel. | Single measurment after a minimum of one week of uninterrupted dual antiplatelet therapy 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Cohort Single cohort will receive Blood draw only.
Blood draw only: Blood draw only | 100 |
| Total | 100 |
Baseline characteristics
| Characteristic | Single Cohort | — |
|---|---|---|
| Age, Continuous | 67.2 years STANDARD_DEVIATION 11.3 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 100 Participants | — |
| Sex: Female, Male Female | 50 Participants | — |
| Sex: Female, Male Male | 50 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 100 |
| other Total, other adverse events | 0 / 100 |
| serious Total, serious adverse events | 0 / 100 |
Outcome results
Primary
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.
Time frame: Single measurment after a minimum of one week of uninterrupted dual antiplatelet therapy with aspirin and clopidogrel
Population: High on-treatment platelet reactivity on clopidigrel (HPRC) was defined as VerifyNow®P2Y12 reactive units (PRU) \>208 and VASP-platelet reactivity index (VASP-PRI) \>50%.~Thromboxane A2 (TXA2) inhibition was measured with the VerifyNow®aspirin test and High on-treatment reactivity on aspirin (HPRA) was defined as aspirin reaction units (ARU) \>550.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single Cohort | Asses the Prevalence of High On-treatment Platelet Reactivity in Critical Limb Ischemia Patients Treated With Aspirin and Clopidogrel. | HPR on Clopidogrel | 18 Participants |
| Single Cohort | Asses the Prevalence of High On-treatment Platelet Reactivity in Critical Limb Ischemia Patients Treated With Aspirin and Clopidogrel. | HPR on Aspirin | 17 Participants |
| Single Cohort | Asses the Prevalence of High On-treatment Platelet Reactivity in Critical Limb Ischemia Patients Treated With Aspirin and Clopidogrel. | HPR on Both | 8 Participants |
| Single Cohort | Asses the Prevalence of High On-treatment Platelet Reactivity in Critical Limb Ischemia Patients Treated With Aspirin and Clopidogrel. | API on Both | 57 Participants |