Clinical trial NCT03331666: Impact of LDL-cholesterol Lowering on Platelet Activation
Official title: Impact of LDL-cholesterol Lowering on Platelet Activation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Familial Hypercholesterolemia
Keywords: Hyperlipidemia, Hypercholesterolemia, atherothrombosis
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2017-11-06
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: The primary goal is to assess the impact of Evolocumab therapy on platelet function of familial hypercholesterolemia (FH) patients in a randomized, double blind study. Evolocumab is a humanized monoclonal antibody that targets circulating PCSK9, increases hepatic LDL receptor, decreases plasma LDL cholesterol and reduces risk of cardiovascular events. Evolocumab (brand name Rapatha) has been approved by FDA along with diet and maximally tolerated statin therapy in adults with FH or atherosclerotic heart or blood vessel problems, who need additional lowering of LDL cholesterol.

The secondary goal is to determine if platelet activation or the response to Evolocumab therapy is modified by rs3184504 polymorphism. The investigators believe that these investigations will complement ongoing studies to demonstrate that Evolocumab reduces athero-thrombotic risk and aid the decision-making as to whether Evolocumab can reduce the atherothrombotic risk in acute coronary syndrome (ACS) patients.

Detailed description: Hyperlipidemia as exemplified by familial hypercholesterolemia is associated with increased platelet activation and an underlying pro-coagulant state. Hyperlipidemia primes platelets and increases platelet activation in response to various agonists. Plasma cholesterol levels appear to have a critical role in modulating platelet activity as hypercholesterolemia increases platelet activation more potently than hypertriglyceridemia. Increased platelet reactivity may contribute to the increased risk of atherothrombosis associated with hypercholesterolemia. Plasma levels of platelet activation markers such as thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), soluble CD40L (sCD40L) or P-selectin exposure at surface of platelets are increased in hypercholesterolemic patients. Increased levels of the platelet activation markers are associated with increased platelet membrane cholesterol content in hypercholesterolemia.Statins may show antithrombotic properties.

Eligibility criteria: Inclusion Criteria:

* Subjects who have a clinical diagnosis of familial hypercholesterolemia (FH)
* Subjects who are referred to Dr. Ginsberg's Lipid Practice for treatment with PCSK9 inhibitor
* Subjects with LDL cholesterol levels \>100 mg/dl on baseline treatment with statins and/or ezetimibe

Exclusion Criteria:

* Children under 18 years of age

Primary outcomes:
measure: Adenosine Di-phosphate (ADP) Induced, P2Y12 Dependent and Arachidonic Acid Induced Platelet Activation (P2Y12 Reaction Units (PRU))
timeFrame: Day 7, Day 14, Day 21, Day 28, Day 84
measure: Adenosine Di-phosphate (ADP) Induced, P2Y12 Dependent and Arachidonic Acid Induced Platelet Activation (Aspirin Reaction Unit (ARU))
timeFrame: Day 7, Day 14, Day 21, Day 28, Day 84
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
affiliation: Columbia University
name: Henry Ginsberg, MD
role: STUDY_DIRECTOR
affiliation: Columbia University
name: Nan Wang, PhD
role: PRINCIPAL_INVESTIGATOR
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