Effects of Evolocumab on Platelet Reactivity in Patients With Diabetes Mellitus (ISS-DMII)

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetes Mellitus, Type 2; Percutaneous Coronary Intervention; Dyslipidemia Associated With Type II Diabetes Mellitus
• Intervention / Treatment: Drug: Evolocumab; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Inova Health Care Services

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): October 1, 2019

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: August 21, 2017
• First Posted (Actual): August 23, 2017

Study Record Updates

• Last Update Posted (Actual): January 19, 2023
• Last Update Submitted That Met QC Criteria: December 22, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Lipid Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 2; Dyslipidemias; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Evolocumab
• Other Study ID Numbers: 17-2639

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No