Effects of High-dose n-3 Fatty Acids on Clinical Outcome and Serum Lipids - Omacor Following Acute Myocardial Infarction (OFAMI)
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First Received Date ICMJE | August 18, 2011 | ||||
Last Updated Date | February 18, 2012 | ||||
Start Date ICMJE | September 1995 | ||||
Primary Completion Date | December 1997 (final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Fatal and non-fatal cardiac events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ] Cardiac events were defined as cardiac death, resuscitation, recurrent myocardial infarction (MI) and unstable angina pectoris, presented as single or combined cardiac events. Revascularizations and death from other causes were also recorded. |
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | Complete list of historical versions of study NCT01422317 on ClinicalTrials.gov Archive Site | ||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Descriptive Information | |||||
Brief Title ICMJE | Effects of High-dose n-3 Fatty Acids on Clinical Outcome and Serum Lipids - Omacor Following Acute Myocardial Infarction | ||||
Official Title ICMJE | Effects of a High-dose Concentrate of n-3 Fatty Acids or Corn Oil Introduced Early After an Acute Myocardial Infarction on Serum Triacylglycerol and High-density Lipoprotein (HDL)- Cholesterol | ||||
Brief Summary | The object of this study was to evaluate the effect of a high-dose ethylester concentrate of of n-3 fatty acids administered early after an acute myocardial infarction on subsequent cardiac events and serum lipids.The second purpose of this study was to assess the impact of high-dose n-3 fatty acids on several markers of coagulation, inflammation, endothelial dysfunction and lipid peroxidation. Re-investigation was intended after a prolonged wash-out-period. |
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Detailed Description | Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 unsaturated fatty acids reduce the risk of cardiovascular disease(CVD) and may improve prognosis. N-3 fatty acids have several beneficial cardiovascular properties (1-3), including antiatherothrombotic, antiarrhythmic, and antihypertensive effects, and are especially noted for their triacylglycerol-reducing ability (3-7). These effects may translate into an improved clinical outcome in patients with coronary artery disease (CAD) (8). The pronounced effect obtained of moderate doses of n-3 fatty acids supplementation may suggest an even stronger effect of pharmacologic doses. The object of this study was therefore to assess the effect of a high-dose ethylester concentrate of n-3 fatty acids as compared to corn oil administered early (4-8 days) after an acute myocardial infarction (MI), on fatal and non-fatal subsequent cardiac events (cardiac death, resuscitation, recurrent myocardial infarction (MI) or angina pectoris), during 2 ys follow-up (median 18 months). We hypothesized that a high-dose of n-3 fatty acids would improve serum lipids in this population, and beneficially influence several markers of coagulation, endothelial dysfunction and inflammation. Three hundred patients with an acute myocardial infarction (MI) were recruited at one hospital center (Central Hospital in Rogaland, Stavanger, Norway) from September 1995 until December 1996. All patients were included between the fourth and the eighth day after an acute myocardial infarction (MI). All patients were randomly assigned to receive 2 gelatin capsules of Omacor-R (Pronova AS, Oslo) or corn oil twice a day. Each capsule contained either 850-882 mg eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as ethylesters in the average ratio of eicosapentaenoic acid (EPA) to docosahexaenoic acid (DHA) of 1:2 or the same amount of corn oil. α-Tocopherol (4 mg) was added to all capsules. The capsules were administered in a double-blind manner over 12-24 months. A detailed patient history was recorded and a clinical examination was performed. The electrocardiogram was scrutinized for infarct location. The recent injury was classified as an anterior or inferior Q-wave infarction or any non-Q-wave infarction. Treatment was initiated immediately after inclusion and collection of baseline blood samples. The study was approved by the Regional Ethics Committee for Western Norway. Clinical follow-up, including blood tests and electrocardiogram recordings, was repeated at 6 wk, 6 mo, 1 y, 18 mo, and, for some patients, 2 ys after the start of treatment. A deviation of 2 wk at the first follow-up and ≤1 mo at later follow-ups was allowed. All cardiac events and ongoing medication were recorded. Cardiac events were defined as cardiac death, resuscitation, recurrent myocardial infarction (MI), and unstable angina. Revascularization and death from other causes were also recorded. The study was closed at the end of 1997. The median follow-up time (ignoring events except deaths) was 1.5 y. Analyses of serum triacylglycerols, total cholesterol and high-density lipoprotein (HDL)-cholesterol were performed at inclusion, 6 weeks, 6 and 12 months. In addition, analyses of markers of inflammation [high-sensitivity-C-reactive protein (CRP), CD-40 Ligand (CD40L)], coagulation [D-Dimer, fibrinogen, tissue factor, activated factor XII (FXIIa)], endothelial dysfunction [adhesion molecules such as E-selectin and Intra-Cellular Adhesion Molecule-1 (ICAM-1), homocysteine)], and Thiobarbituric Acid Reactive Substances (TBARS) as a marker of the oxidative burden of n-3 fatty acids, have been performed at different time points during follow-up, to evaluate the influence of n-3 fatty acids on these markers, and to assess their prognostic ability following a myocardial infarction (MI). Moreover, holo-transcobalamin (holoTC), methylmalonic acid (MMA), n-Terminal pro-Brain Natriuretic Peptide (NT-proBNP), matrix metalloproteinases-9 (MMP-9), Pregnancy-associated plasma protein A (PAPP-A), myeloperoxidase (MPO), and CD40 Ligand (CD40L) were measured also in order to evaluate their prognostic ability following a myocardial infarction (MI). After closure of the main study, the purpose was to evaluate the prognosis of the study subjects after a prolonged wash-out period. Publications from the study:
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Study Type ICMJE | Interventional | ||||
Study Phase | Phase 3 | ||||
Study Design ICMJE | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Publications * |
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Completed | ||||
Enrollment ICMJE | 300 | ||||
Completion Date | December 2002 | ||||
Primary Completion Date | December 1997 (final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Gender | Both | ||||
Ages | 18 Years and older | ||||
Accepts Healthy Volunteers | No | ||||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
Location Countries ICMJE | Norway | ||||
Administrative Information | |||||
NCT Number ICMJE | NCT01422317 | ||||
Other Study ID Numbers ICMJE | OFAMI1995 | ||||
Has Data Monitoring Committee | Yes | ||||
Responsible Party | Helse Stavanger HF | ||||
Study Sponsor ICMJE | Helse Stavanger HF | ||||
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Investigators ICMJE |
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Information Provided By | Helse Stavanger HF | ||||
Verification Date | February 2012 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |