Clinical trial NCT04007055: The Value of Screening for HPR in Patients Undergoing Lower Extremity Arterial Endovascular Interventions
Official title: The Value of Screening for "High on Treatment Platelet Reactivity" in Patients Undergoing Lower Extremity Arterial Endovascular Interventions
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Peripheral Artery Disease
Clopidogrel, Poor Metabolism of
Peripheral Vascular Disease
Artery Disease
Peripheral Arterial Occlusive Disease
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: SCREENING

Brief summary: This is a randomized controlled trial designed to evaluate the role of screening for and intervening on patients with high on treatment platelet reactivity undergoing lower extremity arterial endovascular interventions.

Detailed description: Peripheral arterial disease (PAD) affects millions of people worldwide. Management of PAD has evolved from open surgery to an endovascular first approach leading to increased volume of endovascular interventions. Endovascular femoropopliteal intervention has emerged as a standard treatment for symptomatic PAD with acceptable patency rates.

Histologic observation of bare metal stents with early failure shows association with platelet rich thrombus, high counts of platelets, and neutrophils associated with stent struts. Additionally, high inflation pressures associated with balloon angioplasty often causes local tissue damage leading to platelet activation. These findings led to studies targeting platelet activation following endovascular treatment showing improved outcomes in patients receiving stronger platelet inhibition.

The current standard of care is prescription of dual antiplatelet therapy (DAPT) for femoropopliteal angioplasty or stenting. DAPT is active use of any two antiplatelet agents, often low dose aspirin plus P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel). There is improved stent patency and reduced adverse cardiovascular events in patients taking DAPT versus aspirin monotherapy.

Clopidogrel is the most common additional antiplatelet agent prescribed, but 4-65% of patients taking clopidogrel fail to achieve clinically expected platelet inhibition. This persistent platelet reactivity despite compliant antiplatelet use is commonly referred to as high on-treatment platelet reactivity (HPR), and increases risk of endovascular intervention failure and associated adverse clinical events in these patients. Clopidogrel is a pro-drug metabolized by CYP2C19 enzyme into its active form. Failure to respond appropriately to clopidogrel is largely due to genetic polymorphisms within CYP2C19 enzyme resulting in variable metabolization of clopidogrel into the active metabolite.

Alternative antiplatelet medications can overcome HPR through different metabolic pathways, but unfortunately at a significantly higher cost. Of these, ticagrelor is often used to overcome HPR for patients taking clopidogrel with favorable outcomes. However, regional cost for ticagrelor is $352.50 compared to $1.96 for clopidogrel. Cost and bleeding concerns among providers have prevented widespread use. Overall, there is paucity of evidence looking at HPR and lower extremity arterial endovascular interventions without consensus or guidelines on how to address this problem. Thus, the investigators propose an unblinded, randomized controlled trial in patients having femoropopliteal angioplasty or stenting comparing two strategies: 1. testing and treating for HPR versus 2. guideline based therapy without testing for HPR.

Eligibility criteria: Inclusion Criteria:

* Peripheral arterial disease
* Planned angioplasty or stenting of superficial femoral artery or popliteal artery.

Exclusion Criteria:

* Patients treated on an emergency basis
* Planned intervention on prior site of open surgical intervention (autogenous or autologous bypass, endarterectomy, or patch angioplasty)
* Planned intervention at site exclusive of superficial femoral artery or popliteal artery
* Planned re-stenting at site of prior stent placement
* Planned re-angioplasty at site of prior angioplasty
* Known inability to tolerate antiplatelet regimen before enrollment
* Patients who plan on receiving follow up care outside the University of Pittsburgh Medical Center
* Current use of prasugrel or ticlopidine
* Current use of oral anticoagulation medication
* Pregnant patients

Primary outcomes:
measure: Proportion of participants with primary patency
timeFrame: one year from intervention
Secondary outcomes:
measure: proportion of participants with amputation
timeFrame: one year from intervention
measure: Correlation of HPR testing results
timeFrame: after study completion
measure: Major adverse cardiovascular events
timeFrame: one year from intervention
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
Study officials:
References: