Lovaza's Effect on the Activation of Platelets

NCT00515541 | Completed Phase 2 Results DMC

• 1 other identifier: 07-1068
• Study Type: interventional
• Target: 43
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is to determine the effects of Lovaza in platelet function studies

Conditions

Cardiovascular Disease; Bleeding

Keywords

Platelet; Cardiovascular; Lipid; Fish Oil; Omega 3; DHA; EPA; Bleeding; Clotting; platelet function; Lipid profile; Weight and Bleeding risk

Outcome Measures

Primary Outcomes (3)

• Platelet Aggegation (Arachiodonic Acid)Using a PAP-8E (BioData Corp.)

  The PAP-8E measures platelet aggregation in platelet rich plasma (PRP). Platelet responses to a series of common agonists cause changes in optical density that are measured. The instrument is blanked (100% baseline (optimal transmission)) by inserting a platelet poor plasma (PPP) specimen into the appropriate channel. The PRP is then inserted into the same well. The difference in optical density between the PPP and the PRP 0% baseline (optical transmission) is recorded for several minutes when the agonist reagent is added to the PRP.

  up to and including closeout at 24 weeks

• Bleeding Time

  Bleeding time is a measure of how well platelets interact with blood vessel walls to form a clot. A manual blood pressure cuff is placed 2 inches above the antecubital fossa and inflated to 40mmHg. Using a standard Surgicutt device, a small incision is made and a stopwatch is started. The incision edge is blotted at 30 second intervals with standard filter paper until the bleeding has stopped. The time to hemostasis is noted.

  up to and including closeout at 24 weeks

• EQELS (Electrophoretic Quasi Elastic Light Scattering: Change in Mobility After the Addition of Arachidonic Acid

  Measurements were made using a modified device (EQELS) to specifications of constant current, high electric field and a scattering angle of 30 degrees. EQELS provides a sensitive assessment of subtle changes in the cell surface that occurs with activation, ligand binding or apoptosis. These changes are the result of different distributions of charged groups that define a surface charge finger print for the current state of activation of the cell. Resting state platelets have a negative surface charge, whereas fully activated platelets have a positive surface charge.

  up to and including closeout at 24 weeks

Secondary Outcomes (1)

• The Occurence of Any Type of Bleeding

  up to and including closeout at 24 weeks

Study Arms (4)

A

ACTIVE COMPARATOR

Patient is not on Aspirin, Clopidogrel, or Warfarin and is taking escalating doses of study drug.

Drug: Lovaza

B

ACTIVE COMPARATOR

Patient is on regular dose of Aspirin ( \< or = 325mg). Patient is not taking Clopidogrel or Warfarin and is taking the escalating doses of Lovaza

Drug: Lovaza

C

ACTIVE COMPARATOR

Patient is taking regularly 75mg of clopidogrel daily and Aspirin (\< or = 325mg) and not taking Warfarin and is taking the escalating doses of Lovaza

Drug: Lovaza

D

ACTIVE COMPARATOR

Patient is regularly taking Warfarin daily and Aspirin (\< or = 325mg)and is not taking Clopidogrel and is taking the escalating doses of Lovaza

Drug: Lovaza

Interventions

Lovaza DRUG

First 6 weeks period take 1 gram Lovaza capsule daily 2nd 6 weeks period take 2 grams of Lovaza (2 1 gram capsules) daily 3rd 6 weeks period take 4 grams of Lovaza (4 1 gram capsules) daily 4th 6 weeks period take 8 grams of Lovaza (8 1 gram capsules) daily

A; B; C; D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females older than 18 years old who are able to ingest omega n3 fatty acids are eligible for this trial and are:
• On no antiplatelet and anticoagulation therapy, OR
• On chronic therapy with warfarin or aspirin alone (\< or =325 mg/day)or combination therapy with clopidogrel and aspirin (\< or =325 mg/day).
• The subject must be able to read, understand, and sign an informed consent form and follow protocol.
• To be enrolled in the study, subjects must be clinically stable on stable medical therapy throughout the duration of the study and meet the following criteria:
• Healthy volunteers
• Volunteers with stable coronary artery disease are those with:
• Prior MI (\>1 month) OR
• Prior revascularization: angioplasty ± stenting (\> 1 month) OR
• Coronary artery bypass grafting (\>3 months) OR
• Documented disease on coronary angiography.
• No planned no planned procedures or changes in medical therapies over the 24-week duration of the study
• Volunteers with stable atrial fibrillation are those with:
• Rate-controlled or paroxysmal atrial fibrillation on stable antiarrhythmic therapy.
• On a stable dose of warfarin and regular follow-up in an anticoagulation ("coumadin") clinic.

You may not qualify if:

• Any medical condition that would preclude ingestion of omega n3 fatty acids (Lovaza®).
• Subjects taking nutritional supplements of fish oil or flaxseed oil. These patients may become eligible if they are willing to discontinue these nutritional supplements for a 2-week washout period.
• Any other medical condition that would adversely affect the study objectives.
• Chronic medical conditions known to be associated with abnormal platelet function including:
• Liver dysfunction including abnormal liver function tests (AST, ALT, or alkaline phosphatase \> upper limit of normal), known cirrhosis or chronic hepatitis.
• Chronic kidney disease with a calculated creatinine clearance \< 60 ml/min (MDRD) and/or a serum creatinine \> 2.0 mg/dl.
• History of significant anemia, or baseline hemoglobin \< 11.0 g/dl.
• Baseline PT\>ULN, INR\>1.3, and aPTT\>ULN in subjects who are not on chronic warfarin therapy.
• History of thrombocytopenia, or baseline platelet count of \< 100,000
• History of thrombocytosis, or baseline platelet count of \> 600,000
• Known bleeding diathesis and/or congenital hemostasis disorder and/or congenital platelet abnormalities.
• Any history of stroke in the past 12 months.
• History of peptic ulcer disease in the past year or gastrointestinal bleeding in the last 3 months.
• Genitourinary bleeding in the last 3 months.
• HIV or other infectious diseases that would expose laboratory personnel to unacceptable risks.

Sponsors & Collaborators

• Invitrox: lead
• Reliant Pharmaceuticals: collaborator

Related Publications (1)

• Cohen MG, Rossi JS, Garbarino J, Bowling R, Motsinger-Reif AA, Schuler C, Dupont AG, Gabriel D. Insights into the inhibition of platelet activation by omega-3 polyunsaturated fatty acids: beyond aspirin and clopidogrel. Thromb Res. 2011 Oct;128(4):335-40. doi: 10.1016/j.thromres.2011.04.023. Epub 2011 May 28.

  PMID: 21621252 RESULT

MeSH Terms

Conditions

Cardiovascular Diseases; Hemorrhage; Thrombosis; Body Weight

Interventions

Omacor

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Embolism and Thrombosis; Vascular Diseases; Signs and Symptoms

Limitations and Caveats

Major limitation for this pilot study was the small number of patients analyzed per group. Despite the small numbers we were able to show the statistical significance for a change in the platelet surface charge with Lovaza.

Results Point of Contact

• Title: Dr. Don A. Gabriel
• Organization: Invitrox, Inc

dgabriel@invitrox.com

(919) 485-4600

Study Officials

• Mauricio Cohen, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2007
• First Posted: August 13, 2007
• Study Start: September 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: July 9, 2013
• Results First Posted: July 9, 2013

Record last verified: 2013-06