The Effects of Lovaza® in Acute Myocardial Infarction

Phase 1

Terminated

Conditions: Myocardial Infarction

Interventions: Drug: Lovaza®
Drug: The placebo contained 1 gram of corn oil in each capsule.

Registration Number: NCT01155336

Lead Sponsor: University of Rochester

Brief Summary: This study will explore the safety and effectiveness of adding Lovaza® to the therapeutic program utilized internationally for the treatment of individuals with acute coronary syndromes.

Detailed Description: Atherosclerotic cardiovascular disease is the cause for over 19 million deaths in the US annually with coronary artery disease accounting for most of this mortality burden.1 Despite major advances in the treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. For those who arrive alive at an emergency department, a benefit is accrued from an orchestrated program of live-saving therapeutics designed to preserve ischemic or infarcted myocardium and prevent ventricular arrhythmias. However, despite improvements in door-to-balloon (angioplasty) times in the past decade, reductions in in-hospital mortality have not materialized.2 Average 30-day mortality from ST elevation MI has been shown to be approximately 7% despite the modern aggressive approach of utilizing acute pharmacologic and percutaneous interventions as well as a comprehensive approach to risk factor modification.3 Antiplatelet agents including aspirin, clopidogrel, heparin, and IIb/IIIa inhibitors represent stalwart components of the acute coronary syndrome therapeutic treatment program. At the same time, the safety of combination antiplatelet agents used acutely and chronically in individuals with an acute coronary syndrome is concerning as bleeding complications can result in serious, life-threatening consequences.4 Studies have shown that patients treated with the combination of aspirin and clopidogrel have a small but significant increased risk of major and minor bleeding compared to each agent alone.4-6 In contrast, the use of fish oil in conjunction with aspirin and clopidogrel in patients with cardiovascular disease followed for an average of 33 months has been shown to have no significant effect on risk of major and minor bleeding compared to those on aspirin and clopidogrel alone, with a trend toward a reduced risk of minor bleeding in those taking fish oil.4 In Preliminary Data it is shown that a robust synergistic effect between Lovaza® and aspirin on the downregulation of platelet function may occur. These data suggest that the most potent omega-3 fatty acids found in fish oil (eicosapentaenoic acid {EPA} and docosahexaenoic acid {DHA}) act acutely to modulate a major contributor to the pathophysiology of acute coronary syndromes. This study will randomize 60 patients with ST elevation myocardial infarction to treatment with Lovaza® or placebo and measure the differences in platelet function and electrophysiologic parameters between treatment arms during their acute hospitalization and 1 week after discharge.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

Inclusion Criteria

Acute myocardial infarction documented by at least 2 of the following:
1. Typical symptoms
2. Abnormal levels of cardiac biomarkers (troponin I or T or CK-MB mass) with at least one determination > 99th percentile or ULN for the laboratory
3. ECG findings diagnostic of myocardial infarction based on the American College of Cardiology criteria.
Status-post urgent or emergent PCI
Have a Thrombolysis In Myocardial Infarction (TIMI) flow grade = 3 (complete perfusion) post PCI.
Have the capacity for informed consent (e.g. without significant dementia or sedation from medication)
Ingested 325 mg of chewed aspirin as part of the acute coronary syndrome treatment protocol.

Exclusion Criteria

No informed consent
Daily aspirin use prior to index hospitalization
Known prior myocardial infarction
Known pregnancy
Known allergy to fish, fish oil, or aspirin
Known active internal or non-superficial bleeding, known bleeding disorder, coagulation defect, or thrombocytopenia
Thrombolysis in the past 12 hours
Treatment with a IIbIIIa inhibitor during index hospitalization
Cardiogenic shock or symptomatic hypotension or sitting SBP < 95 mmHg
Severe uncontrolled hypertension (≥180/110) or hypertensive retinopathy
A history of major surgery, trauma, retinal hemorrhage, significant gastrointestinal (not hemorrhoidal) or genitourinary bleeding in the past 6 weeks
A history of cerebrovascular attack within two years, or cerebrovascular attack with a significant residual neurological deficit
A known arteriovenous malformation or aneurysm
Severe liver insufficiency (ALT ≥ 3 times normal)
Renal insufficiency requiring dialysis
A known diagnosis of vasculitis
Participation in another clinical study
History of malignancy, except subjects who have been disease-free for greater than 10 years, or whose only malignancy has been basal or squamous cell skin carcinoma
Oral contraceptive use
Daily use of NSAIDs
History of drug or alcohol abuse, or current weekly alcohol consumption >14 units/week (1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 shot of alcohol)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lovaza®	Lovaza®	Lovaza® is a prescription grade EPA+DHA fish oil supplement. Four capsules (each containing 1 gram of fish oil) were taken within hours after the PCI, daily for the duration of hospitalization, and daily for 1 week until a post-discharge follow-up appointment.
Corn Oil	The placebo contained 1 gram of corn oil in each capsule.	The placebo contained 1 gram of corn oil in each capsule. Four capsules were taken within hours after the PCI, daily for the duration of hospitalization, and daily for 1 week until a post-discharge follow-up appointment.

Primary Outcome Measures

Name	Time	Method
Platelet Function	12 hours	Platelet function will be measured with PFA-100 test which has been shown to correlate with an increased risk for cardiovascular events in several well conducted studies and in a meta-analysis. The PFA-100 measures the number of seconds required for a clot to form in whole blood which is passed through an aperture in a cartridge coated with epinephrine. It is meant to imitate clotting in human arteries.

Secondary Outcome Measures

Name	Time	Method
Cardiac Electrophysiology	1 week	A 20-minute supine 12-lead Holter ECG will allow the quantification of a series of standard ECG parameters as well as provide insight into frequency-domain HRV parameters, QRS duration and morphology, using signal-averaged ECG (SAECG), repolarization morphology, and variability utilizing specialized programs.