Impact of Evolocumab on the Effects of Clopidogrel in Patients With High On-Treatment Platelet Reactivity

Part of paid clinical trials in Jacksonville, Florida.

Sponsor
University of Florida
Study ID
NCT03096288
Phase
PHASE4
Status
Completed

Conditions

  • Atherosclerotic Cardiovascular Disease

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Evolocumab — DRUG
    Patients will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).
  • Placebo — OTHER
    Patients will be randomly assigned to receive a single dose of either evolocumab 420 mg s.c. or placebo (0.9% sodium chloride s.c. injection).

Study Details

Clopidogrel is the most widely used P2Y12 receptor inhibitor and is the only agent of this class currently recommended in patients with stable coronary artery disease (CAD) undergoing PCI, and for the treatment of stroke or PAD. Pharmacodynamic (PD) studies have shown that approximately 30-40% of patients experience high on-treatment platelet reactivity (HPR) while receiving clopidogrel treatment. Importantly HPR status has been strongly associated with an increased risk of ischemic events. Multiple approaches have been advocated to reduce HPR rates. In a previous study treatment with high-dose atorvastatin in addition to double-dose clopidogrel reduced platelet reactivity significantly more than double-dose clopidogrel alone in statin-naïve patients with stable CAD and HPR. To date, the exact biological mechanisms involved in the statin modulation of platelet function are not fully understood, although likely attributed to both its lipid-lowering and non-lipid-related effects. Evolocumab is a monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). The use of evolocumab plus standard therapy, as compared with standard therapy alone, significantly reduced the incidence of cardiovascular events. Whether the reduction in cardiovascular events is simply due to LDL reduction or might be related to other mechanisms is currently subject of investigation. Although LDL reduction with statin therapies has been associated with reduction in platelet reactivity, to date the effects on platelet aggregation of adjunctive lipid lowering with evolocumab has not been explored. The aim of the present study is to investigate the effects of evolocumab in addition to statin therapy on HPR rates and platelet reactivity in patients with atherosclerotic cardiovascular disease (ASCVD) and HPR while on clopidogrel treatment.

Key Dates

Start date
Oct 3, 2017
Status verified
Feb 2022
Primary completion
Nov 2, 2020
Completion
Nov 2, 2020

Study Design

Enrollment
259 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Evolocumab
    Evolocumab (Repatha) 420 mg s.c. single injection
  • Placebo Comparator: Placebo
    0.9% sodium chloride s.c. single injection

Primary Outcome Measure

Platelet Reactivity Defined by VerifyNow PRU in HPR and NPR Patients [ Time Frame: 30 days ]

Locations (1)

FacilityCityStateZIPSite coordinators
University of FloridaJacksonvilleFlorida32209-

Find similar trials in Jacksonville, FL

By research site
University of Florida· Jacksonville, FL

Related Studies