Impact of LDL-cholesterol Lowering on Platelet Activation

NCT03331666 | Terminated Phase 4 Results DMC FDA Drug

• 1 other identifier: AAAR1041
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Familial Hypercholesterolemia

Keywords

Hyperlipidemia, Hypercholesterolemia, atherothrombosis

Outcome Measures

Primary Outcomes (2)

• Adenosine Di-phosphate (ADP) Induced, P2Y12 Dependent and Arachidonic Acid Induced Platelet Activation (P2Y12 Reaction Units (PRU))

  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))

  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

Study Arms (2)

Evolocumab

ACTIVE COMPARATOR

Subjects will start with placebo and will receive Evolocumab 140 mg every 14 days starting Day 14 until Day 196.

Drug: Evolocumab

Placebo

PLACEBO COMPARATOR

Subjects will start with placebo and will receive Evolocumab 140 mg every 14 days starting Day 28 until Day 196.

Drug: Evolocumab

Interventions

Evolocumab DRUG

140 mg every 14 days A monoclonal antibody designed for the treatment of hyperlipidemia

Also known as: REPATHA

Evolocumab; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Children under 18 years of age

Sponsors & Collaborators

• Columbia University: lead
• Amgen: collaborator

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

Related Publications (20)

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• Pawelczyk M, Chmielewski H, Kaczorowska B, Przybyla M, Baj Z. The influence of statin therapy on platelet activity markers in hyperlipidemic patients after ischemic stroke. Arch Med Sci. 2015 Mar 16;11(1):115-21. doi: 10.5114/aoms.2015.49216. Epub 2015 Mar 14.

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• Pignatelli P, Carnevale R, Pastori D, Cangemi R, Napoleone L, Bartimoccia S, Nocella C, Basili S, Violi F. Immediate antioxidant and antiplatelet effect of atorvastatin via inhibition of Nox2. Circulation. 2012 Jul 3;126(1):92-103. doi: 10.1161/CIRCULATIONAHA.112.095554. Epub 2012 May 21.

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• Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, Monsalvo ML, Tsirtsonis K, Kim JB, Scott R, Wasserman SM, Stein EA; DESCARTES Investigators. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med. 2014 May 8;370(19):1809-19. doi: 10.1056/NEJMoa1316222. Epub 2014 Mar 29.

  PMID: 24678979 BACKGROUND

• Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, Ballantyne CM, Somaratne R, Legg J, Wasserman SM, Scott R, Koren MJ, Stein EA; Open-Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015 Apr 16;372(16):1500-9. doi: 10.1056/NEJMoa1500858. Epub 2015 Mar 15.

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• Writing Committee; Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr, DePalma SM, Minissian MB, Orringer CE, Smith SC Jr. 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2016 Jul 5;68(1):92-125. doi: 10.1016/j.jacc.2016.03.519. Epub 2016 Apr 1. No abstract available.

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MeSH Terms

Conditions

Hyperlipoproteinemia Type II; Hyperlipidemias; Hypercholesterolemia; Thrombosis

Interventions

evolocumab

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hyperlipoproteinemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Dr. Nan Wang
• Organization: Columbia University Irving Medical Center

nw30@cumc.columbia.edu

212-342-1761

Study Officials

• Henry Ginsberg, MD

  Columbia University

  STUDY DIRECTOR

• Nan Wang, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medical Sciences (in Medicine) at the Columbia University Medical Center

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: November 6, 2017
• Study Start: November 16, 2018
• Primary Completion: February 4, 2020
• Study Completion: February 4, 2020
• Last Updated: April 1, 2021
• Results First Posted: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)