Clinical trial NCT01526824: Lovaza's Effect on Clopidogrel in a Neuro Population
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Ischemic Stroke
Transient Ischemic Attack
Lead sponsor: Millard Fillmore Gates Hospital
Sponsor class: OTHER
Collaborators: name: Kaleida Health
First posted: 2012-02-06
Enrollment: 60
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: PRU and % inhibition of P2Y12 Assay
timeFrame: 20-30 days after initiation of the study
Secondary outcomes:
measure: Neurologic events in each study
timeFrame: 20-30 days after initiation of study
measure: HDL, triglycerides, LDL, or total cholesterol
timeFrame: 20-30 days after initiation of the study
measure: Bleeding
timeFrame: 20-30 days
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Millmore Fillmore Gates Hospital
state: New York
Study officials:
affiliation: Millmore Fillmore Gates Hospital
name: Melissa Baxter, PharmD
role: PRINCIPAL_INVESTIGATOR
References: