Effects of Evolocumab on Platelet Reactivity in Patients With Diabetes Mellitus

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

1. the effect of evolocumab therapy on platelet activation and reactivity;
2. the effect of evolocumab on biomarkers of platelet activation and inflammation.

Eligible patients will be randomized prior to start the PCI equally to either:

1. 420 mg evolocumab ; or
2. 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.

• Evolocumab (Drug), also known as Repatha: Patients will receive evolocumab 420 mg administered subcutaneously
• Placebo (Drug): Patients will receive placebo administered subcutaneously

Primary outcomes

• Change From Baseline in Adenosine Diphosphate (ADP) Stimulated P-selectin Expression [Baseline and after 30 days of treatment]: 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).

Secondary outcomes

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

Sex: All

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

Participant flow

Outcome results

• Change From Baseline in Adenosine Diphosphate (ADP) Stimulated P-selectin Expression (Primary), Mean, % Positive Cells: Evolocumab 420mg 45.2 +/- 17.1; Placebo
• Change in ADP-unstimulated P-selectin Expression (Secondary), Mean, % Positive Cells: Evolocumab 420mg 5.4 +/- 2.7; Placebo
• Change in ADP-stimulated Lectin-like oxLDL [Oxidized Low-density Lipoprotein] Receptor-1 Mean Fluorescence Intensity (MFI) (Secondary), Mean, MFI: Evolocumab 420mg 1186 +/- 1017; Placebo
• Change in ADP-stimulated Cluster of Differentiation (CD)-147 MFI (Secondary), Mean, MFI: Evolocumab 420mg 1459 +/- 1220; Placebo

Adverse events

Time frame: 30 Days

Serious adverse events by term

Other adverse events by term

Limitations and caveats: Study was terminated early as a result of 1) low enrollment and , 2) thrombosis research center moving to another health system (LifeBridge Health) . Only 4 patients were enrolled, as a result we were not able to conduct an analysis on any of the endpoints.

• Study Protocol and Statistical Analysis Plan (PDF, 2018-04-24)
• Informed Consent Form (PDF, 2019-06-19)