Lovaza's Effect on Clopidogrel in a Neuro Population

Millard Fillmore Gates Hospital

Status and phase: Unknown; Early Phase 1

Conditions: Ischemic Stroke; Transient Ischemic Attack

Treatments: Dietary Supplement: omega-3 polyunsaturated fatty acids (Lovaza)

Study type: Interventional

Funder types: Other

Identifiers

NCT01526824

PHP1061010A

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 25 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Control arm, clopidogrel without Lovaza

No Intervention group

Description:

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.

Clopidogrel plus Lovaza

Experimental group

Description:

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.

Treatment:

Dietary Supplement: omega-3 polyunsaturated fatty acids (Lovaza)