Lovaza's Effect on Clopidogrel in a Neuro Population

The Effects of Polyunsaturated Omega-3 Fatty Acids (Lovaza) on Patients Taking Clopidogrel +/- Aspirin Who Have Suffered an Ischemic Stroke/TIA and/or Are Candidates for Neuroendovascular Stenting.

In patients who have suffered an ischemic stroke or TIA (mini-stroke), as well as in patients who are candidates for neuroendovascular stenting, it is standard of care to treat these patients with antiplatelet therapy, or "blood-thinners", the most common of which is clopidogrel (Plavix) with or without the addition of aspirin. A relatively common problem encountered with these patients is non-responsiveness to clopidogrel therapy. A prior study in cardiac patients showed that the addition of omega-3 polyunsaturated fatty acids (Lovaza, or "fish oil") can increase a patient's response to therapy with clopidogrel, but there have been no studies in neuro patients. In this study, patients will be divided into one of two groups: in the study arm, patients will receive clopidogrel +/- aspirin as well as Lovaza. In the control arm, patients will only receive clopidogrel +/- aspirin. Assays will be done to measure responsiveness to clopdiogrel on days 0, 12-24 hours after loading dose, day 3-5 if still inpatient, and at a follow-up visit 20-30 days after the start of the study. The investigators believe that this study will show an increase in platelet aggregation in patients receiving both clopidogrel and Lovaza.

Study Overview

• Status: Unknown
• Conditions: Ischemic Stroke; Transient Ischemic Attack
• Intervention / Treatment: Dietary supplement: omega-3 polyunsaturated fatty acids (Lovaza)

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Melissa Baxter, PharmD; Phone Number: 716-887-4401; Email: MBaxter@kaleidahealth.org

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14209
      • Recruiting
      • Millmore Fillmore Gates Hospital
      • Contact: Melissa Baxter, PharmD; Email: MBaxter@kaleidahealth.org
      • Sub-Investigator: Robert Sawyer, MD
      • Sub-Investigator: Adnan H Siddiqui, MD, PhD
      • Sub-Investigator: Elad I Levy, MD, FACS, FAHA
      • Sub-Investigator: Ken Snyder, MD, PhD
      • Sub-Investigator: Travis Dumont, MD
      • Sub-Investigator: Shannon O'Brien, MD
      • Sub-Investigator: Naveen Sajja, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 23 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Gender: Male and female
• Age range: 25 - 80 years of age
• Study population: Patients who require antiplatelet therapy with clopidogrel +/- aspirin who are candidates for neuroendovascular stenting or have had an ischemic stroke/TIA.
• Eligible females will be: Non-pregnant nor lactating/breastfeeding; Be surgically sterile for at least 6 months, postmenopausal, or if heterosexually active and of childbearing potential, agree to continue to use an accepted method of birth control throughout the study.

Exclusion Criteria:

• Any clinically significant abnormal finding uncovered during the physical examination and/or clinically significant abnormal laboratory result at screening according to the clinical judgment of the Investigators
• Current alcohol abuse
• Smokers unable to refrain from smoking during the clinical trial
• Patients who are already taking anticoagulants or other antiplatelets (ticlopidine, prasugrel, dipyridamole, cilostazol), or patients already taking PUFAs

• Patients taking medications known to interact with clopidogrel that cannot be held or changed due to increased risk of adverse health events.

  • Cytochrome P450 3A4 and 2C19 (CYP3A4, CYP2C19) inhibitors or substrates known to cause competitive inhibition
  • Proton pump inhibitors (PPIs)
  • NSAIDs
• Pregnant women or lactating/breastfeeding women.

• Active or recent major bleeding (within 14 days) using TIMI score (minor severity will be acceptable based on clinical examination/patient history)

  • Major severity-
• Intracranial hemorrhage
• Cardiac tamponade

• Overt bleeding with a decrease in hemoglobin ≥ 5 g/dl or a decrease in hematocrit ≥ 15% (with or without an identifiable site)

  • Minor severity-
• Spontaneous gross hematuria
• Spontaneous hematemesis
• Spontaneous hemoptysis
• Observed bleeding with decrease in hemoglobin ≥ 3 g/dl but ≤ 5 g/dl (with an identifiable site)
• History of gastric or duodenal ulcer
• Platelet count < 100 x 109/L
• Serum creatinine > 2 mg/dL
• Liver injury (alanine transaminase level > 1.5 times upper limit of normal)
• Recent surgery (within 14 days of study screening)

• Known bleeding diathesis including but not limited to

  • Hemophilia
  • Von Willebrand disease
  • Leukemia
  • Clotting factor deficiencies

• Uncontrolled hypertension

  • Sustained systolic blood pressure > 185 mmHg, despite treatment
  • Sustained diastolic blood pressure > 110 mmHg, despite treatment
• Hypersensitivity or intolerance to clopidogrel, aspirin, PUFAs and/or documented fish allergy
• Patients who are currently enrolled in a different study or who have taken an investigational medication 30 days prior to starting this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control arm, clopidogrel without Lovaza; These patients will be receiving standard of care therapy with either standard dose (75mg daily) or high dose (150mg daily) clopidogrel +/- aspirin based on physician discretion.
Experimental: Clopidogrel plus Lovaza; This is the study arm of the trial, in which patients will be receiving either a standard dose (75mg daily) or high dose (150mg daily) clopidogrel with or without aspirin as well as therapy with daily Lovaza.	Dietary supplement: omega-3 polyunsaturated fatty acids (Lovaza); Lovaza, 1 gram orally daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
PRU and % inhibition of P2Y12 Assay	20-30 days after initiation of the study

Secondary Outcome Measures

Outcome Measure	Time Frame
Neurologic events in each study	20-30 days after initiation of study
HDL, triglycerides, LDL, or total cholesterol	20-30 days after initiation of the study
Bleeding	20-30 days

Collaborators and Investigators

• Sponsor: Millard Fillmore Gates Hospital
• Collaborators: Kaleida Health
• Investigators: Principal Investigator: Melissa Baxter, PharmD, Millmore Fillmore Gates Hospital

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): September 1, 2013
• Study Completion (Anticipated): September 1, 2013

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: February 1, 2012
• First Posted (Estimate): February 6, 2012

Study Record Updates

• Last Update Posted (Estimate): February 6, 2012
• Last Update Submitted That Met QC Criteria: February 1, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Stroke; Ischemic Stroke; Ischemia; Ischemic Attack, Transient
• Other Study ID Numbers: PHP1061010A