Impact of LDL-cholesterol Lowering on Platelet Activation

March 5, 2021 updated by: Nan Wang, Columbia University

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Evolocumab
Subjects will start with placebo and will receive Evolocumab 140 mg every 14 days starting Day 14 until Day 196.
Drug: Evolocumab
140 mg every 14 days A monoclonal antibody designed for the treatment of hyperlipidemia
Other Names:
  • REPATHA
PLACEBO_COMPARATOR: Placebo
Subjects will start with placebo and will receive Evolocumab 140 mg every 14 days starting Day 28 until Day 196.
Drug: Evolocumab
140 mg every 14 days A monoclonal antibody designed for the treatment of hyperlipidemia
Other Names:
  • REPATHA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adenosine Di-phosphate (ADP) Induced, P2Y12 Dependent and Arachidonic Acid Induced Platelet Activation (P2Y12 Reaction Units (PRU))
Time Frame: Day 7, Day 14, Day 21, Day 28, Day 84
ADP- or arachidonic acid-stimulated platelet aggregation as assessed by the commercially-available VerifyNow P2Y12 (VerifyNow PRUTest) will be performed. Unit: PRU
Day 7, Day 14, Day 21, Day 28, Day 84
Adenosine Di-phosphate (ADP) Induced, P2Y12 Dependent and Arachidonic Acid Induced Platelet Activation (Aspirin Reaction Unit (ARU))
Time Frame: Day 7, Day 14, Day 21, Day 28, Day 84
ADP- or arachidonic acid-stimulated platelet aggregation as assessed by the commercially-available VerifyNow Aspirin assay (Accriva Diagnostics) will be performed. Unit: Aspirin Reaction Unit (ARU)
Day 7, Day 14, Day 21, Day 28, Day 84

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Columbia University

Collaborators

Amgen

Investigators

  • Study Director: Henry Ginsberg, MD, Columbia University
  • Principal Investigator: Nan Wang, PhD, Columbia University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 16, 2018

Primary Completion (ACTUAL)

February 4, 2020

Study Completion (ACTUAL)

February 4, 2020

Study Registration Dates

First Submitted

October 20, 2017

First Submitted That Met QC Criteria

October 31, 2017

First Posted (ACTUAL)

November 6, 2017

Study Record Updates

Last Update Posted (ACTUAL)

April 1, 2021

Last Update Submitted That Met QC Criteria

March 5, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AAAR1041

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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