Effects of Evolocumab on Platelet Reactivity in Patients With Diabetes Mellitus

Study Overview
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Brief Summary
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Prospective, single center, double-blind, randomized pharmacodynamic experimental study. The study will enroll 150 subjects with ASCVD on optimal statin therapy as per physician and Diabetes Mellitus (DM) undergoing elective Percutaneous Coronary Intervention (PCI). Eligible patients will be randomized for 30 day treatment to either 1) evolocumab 420 mg ; or 2) placebo.

Detailed Description
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This is a double-blind randomized clinical trial of evolocumab versus placebo in patients with ASCVD and DM on clopidogrel and aspirin undergoing PCI. The study is aimed to assess the effect of evolocumab therapy on platelet activation and reactivity; the effect of evolocumab on biomarkers of platelet activation and inflammation. Eligible patients will be randomized prior to start the PCI equally to either: 420 mg evolocumab ; or placebo. The randomized treatment will be administered in subcutaneous injections. The laboratory assessments will be performed before (baseline), and 16-24 hours and 30-days after randomization. Subject participation will be 30 days from the randomization.

Official Title
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Effects of Evolocumab on Platelet Reactivity in Patients With Diabetes Mellitus After Elective Percutaneous Coronary Intervention

Conditions
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Diabetes Mellitus, Type 2, Dyslipidemia Associated With Type II Diabetes Mellitus, Percutaneous Coronary Intervention

Intervention / Treatment
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* Drug: Evolocumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diabetes Mellitus Dyslipidemia Undergoing elective PCI Exclusion Criteria: Patients with recent Acute Coronary Syndrome (≤1 month) Patients on dual antiplatelet treatment (DAPT) with ticagrelor or prasugrel Patients undergoing urgent/emergent PCI for stent thrombosis Severe acute or chronic medical or psychiatric condition Pregnancy Participation in another experimental clinical trial, without formal approval Unwillingness or inability to comply with the requirements of this protocol
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: evolocumab 420mg<br>75 subjects on optimal statin therapy undergoing elective PCI will receive evolocumab 420mg. | Drug: Evolocumab<br>* Patients will receive evolocumab 420 mg administered subcutaneously<br>* Other names: Repatha;|
| Placebo Comparator: placebo<br>75 subjects on optimal statin therapy undergoing elective PCI will receive placebo | Drug: Placebo<br>* Patients will receive placebo administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Adenosine Diphosphate (ADP) Stimulated P-selectin Expression | Change from baseline in ADP-stimulated P-selectin expression (% Positive Cells) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo). | Baseline and after 30 days of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ADP-unstimulated P-selectin Expression | Change in ADP-unstimulated P-selectin expression (% Positive Cells) between treatment groups (420 mg evolocumab treatment and placebo) | Baseline and after 30 days of treatment | 
| Change in ADP-stimulated Lectin-like oxLDL [Oxidized Low-density Lipoprotein] Receptor-1 Mean Fluorescence Intensity (MFI) | Change in ADP-stimulated LOX-1 (MFI) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo) | Baseline and after 30 days of treatment | 
| Change in ADP-stimulated Cluster of Differentiation (CD)-147 MFI | Change in ADP-stimulated CD-147 mean fluorescence intensity (MFI) as measured by flow cytometry between treatment groups (420 mg evolocumab treatment and placebo) | Baseline and after 30 days of treatment |