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Vol 122, No 21

November 23, 2010

result. P-OM3 was safe and well tolerated; 5% of placebo and 4% of P-OM3 treated patients discontinued due to AEs. EPA and DHA blood levels were significantly higher in the P-OM3 group compared to placebo (p0. 001) and heart rate was lower. Conclusion: This study demonstrates no benefit of P-OM3 for the prevention of recurrent AF in subjects without significant structural heart disease. Study funded by GlaxoSmithKline, Research Triangle Park, NC

for whom I am employed part time as a st. L. Mauri: Consulting for Cordis. H. Adams: The chief disclosure is that we are investigators in the trial sponsored by NMT. My other disclosures – Merck and Schering-Plough – research support. G. Albers: My only relevant disclosure information is: consultant for NMT and grant support from NMT (local PI of CLOSURE trial).. R. Felberg: None. H. Herrmann: Research Grant; Modest; Research funding from:. S. Kar: Ownership Interest; Modest; small stock holdings NMT. Consultant/Advisory Board; Modest; SAB member of NMT. M. Landzberg: I have performed research trials associated with NMT, and currently serve on the Executive Committee for CLOSURE I. A. Raizner: NMT Medical Inc. L. Wechsler: NMT Medical Inc. M. Reisman: ; Dr. Reisman provides consulting services for Boston Scientific and Cordis, receiving honorariums for both, and does research for NMT and Coherex and receives no royalties from either.

Late-Breaking Clinical Trials III

Hall B Abstracts 21791–21843

21791 Standard versus High-Dose Clopidogrel According to Platelet Function Testing After PCI: Results of the GRAVITAS Trial

Author Disclosures: P.R. Kowey: Honoraria; Modest; GlaxoSmithKline. Consultant/Advisory Board; Modest; GlaxoSmithKline. J.A. Reiffel: Research Grant; Modest; GlaxoSmithKline. Honoraria; Modest; Sanofi-Aventis, Gilead, GlaxoSmithKline. Consultant/Advisory Board; Mod- est; Sanofi-Aventis, Gilead, GlaxoSmithKline. K.A. Ellenbogen: Research Grant; Significant; Boston Scientific Corporation, Biosense Webster, Medtronic, Inc., St. Jude Medical, Sanofi- Aventis. Speakers Bureau; Modest; Medtronic, Inc., Boston Scientific, St. Jude Medical, Biotronik. Honoraria; Modest; Medtronic, Inc., Boston Scientific Corporation, St. Jude Medical, Biosense Webster, Sanofi-Aventis. Consultant/Advisory Board; Modest; Boston Scientific Corporation, Biosense Webster, Medtronic, Inc., Sanofi-Aventis, St. Jude Medical, Cardionet, Atritech, EBR, Biotronik, Sorin Biomedical, GlaxoSmithKline. G.V. Naccarelli: Research Grant; Modest; GlaxoSmithKline. Consultant/Advisory Board; Modest; GlaxoSmithKline. C.M. Pratt: Merck, Sanofi-Aventis. Other; Modest; GlaxoSmithKline.

21752 CLOSURE I: A Prospective, Multicenter, Randomized Controlled Trial to Evaluate the Safety and Efficacy of the STARFlex® Septal Closure System versus Best Medical Therapy in Patients With a Stroke or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale

Anthony Furlan, Univ Hosps Case Neurological Institute, Cleveland, OH; Joseph Massaro, Harvard Clinical Rsch Institute, Boston,, MA; Laura Mauri, HCRI, Boston, MA; Harold Adams, Univ of Iowa, Iowa City, OH; Gregory Albers, Stanford, Palo Alto, CA; Robert Felberg, Geisinger, Danville, PA; Howard Herrmann, Univ of Pennsylvania, Philadelphia, PA; Saibal Kar, Cedars Sinai Med Cntr, LosAngeles, CA; Michael Landzberg, Brigham and Women’s Hosp, Boston, MA; Albert Raizner, Methodist Hosp, Houston, TX; Lawrence Wechsler, Univ of Pittsburgh, Pittsburgh, PA; Mark Reisman; Swedish Med Cntr, Seattle, WA

Background: Some strokes with unknown etiology (cryptogenic) may be the result of paradoxical embolism traversing through a patent foramen ovale (PFO). The utility of percutaneous devices for secondary prevention in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO compared to medical therapy alone is not known. CLOSURE I is the first completed randomized controlled trial comparing the safety and efficacy of percutaneous PFO closure to medical therapy alone for secondary TIA and stroke prevention in patients with PFO. The main results of CLOSURE I will be presented. Study Objective: The primary objective of CLOSURE I is to determine whether percutaneous PFO closure utilizing the STARFlex® Septal Closure System in combination with medical therapy is superior to medical therapy alone for the prevention of recurrent TIA, stroke, and mortality in patients with cryptogenic TIA or stroke and PFO. Study Design: CLOSURE I is a prospective, multi-center, randomized, open-label, two-arm superiority trial. The study population includes patients with a cryptogenic TIA or stroke and PFO documented by TEE, with or without atrial septal aneurysm, within 6 months of randomization. Between June 23, 2003 and October 24, 2008, 910 patients age 18–60 were randomized at 87 sites in the USA and Canada to either medical therapy (aspirin 325 mg daily or warfarin target INR 2.0–3.0 or a combination of the two) or to percutaneous PFO closure utilizing STARFlex® plus medical therapy (clopidogrel 75 mg for 6 months and aspirin 325 mg for two years). Follow up visits were at 1 month (phone), 6 months, 12 months, and 24 months. The primary endpoint is the 2-year rate of stroke or TIA, all cause mortality for the first 30 days, and neurological mortality 31 days. Conclusions: CLOSURE I will provide the first randomized controlled trial evidence as to whether percutaneous closure using the STARFlex® Septal Closure System is safe and more effective than medical therapy alone in preventing a recurrent stroke or TIA and mortality in patients with PFO.

Author Disclosures: A. Furlan: Consultant/Advisory Board; Modest; Consultant NMT Medicla Inc

  • 10,000/year. J. Massaro: I was paid for my work on this project as a statistician through

Harvard Clinical Research Institute, who was the data coordinating center for this project and

Matthew J Price; Scripps Clinic, La Jolla, CA

Background: Observational, single-center studies have suggested an association between high residual platelet reactivity on clopidogrel therapy and cardiovascular events after percutaneous coronary intervention. Methods: In this multicenter, blinded, placebo-controlled, randomized trial, we compared high-dose clopidogrel (additional loading dose, 150-mg daily thereafter) with standard-dose clopidogrel (no additional loading dose, 75-mg daily thereafter) for the prevention of cardiovascular events after percutaneous coronary intervention with drug-eluting stents in 2,214 patients with high residual platelet reactivity according to the VerifyNow P2Y12 Test (Accumetrics, San Diego, CA), measured 12 to 24 hours after the procedure. A cohort of 586 patients without high residual platelet reactivity selected at random were also enrolled and treated in a blinded fashion with standard-dose clopidogrel (75-mg daily). The primary efficacy endpoint was a composite of death from cardiovascular causes, myocardial infarction, or stent thrombosis at 6 month follow-up. Results: The primary results of the trial will be presented. Conclusions: GRAVITAS is the first large-scale clinical trial designed to examine whether adjustment of antiplatelet therapy on the basis of platelet function testing using a point-of-care assay improves outcomes after PCI with DES.

Author Disclosures: M.J. Price: Research Grant; Modest; Accumetrics. Research Grant; Significant; BMS/Sanofi-aventis. Speakers Bureau; Significant; DSI/Eli Lilly. Honoraria; Modest; The Medicines Company. Consultant/Advisory Board; Modest; BMS/Sanofi-aventis. Consultant/ Advisory Board; Significant; DSI/Eli Lilly, Accumetrics.

21790 NV1FGF Gene Therapy on Amputation-Free Survival in Critical Limb Ischemia - Phase 3 Randomized Double-Blind Placebo-Controlled Trial

William R Hiatt, Univ of Colorado Denver, Denver, CO; Iris I Baumgartner, Univ Hosp, Berne, Switzerland; Sigrid Nikol, Asklepios Klinik St. Georg, Hamburg, Germany; Eric Van Belle, Hosp Cardiologique, CHRU de Lille, France; Vickie R Driver, Boston Univ Sch of Medicine, Boston, MA; Lars Norgren, Univ Hosp, Orebro, Sweden; Jill J Belch; Univ of Dundee, Dundee, United Kingdom

Background: Patients with critical limb ischemia (CLI) and skin lesions, unsuitable for revascularization have a high rate of amputation and mortality. Local gene therapy using non-viral plasmid DNA encoding acidic fibroblast growth factor (riferminogene pecaplasmid, also known as NV1FGF) demonstrated positive phase 2 results on both amputation and mortality in CLI. The TAMARIS phase 3 trial tested the hypothesis that intramuscular injection of NV1FGF would confirm the benefit on amputation-free survival in CLI. Methods: This was a large international trial involving 170 sites in 30 countries, enrolling 525 patients (523 treated) with CLI unsuitable for revascularization who had stable ischemic skin lesions. Patients were included who had a lower extremity ischemic ulcer and met hemodynamic criteria of an ankle pressure 70 mmHg and/or a toe pressure 50 mmHg or a transcutaneous oxygen pressure 30mmHg in the treated leg. Patients were randomized double-blind to receive 8 intramuscular injections on the same leg of either 2.5 ml NV1FGF at 0.2 mg/ml or placebo on Days 1, 15, 29, and 43. The primary endpoint was the reduction of major amputation or death, whichever came first, at 1 year analysed with a log rank test using a multivariate Cox proportional hazard model. The sample size was based on an assumed annual event rate of 51.5% on placebo and 33.2% on NV1FGF (90% power, alpha 5%). Results: Patients had a mean age of 7010 years, 70% were male, 53% had diabetes, 61% had a history of smoking and 54% had a history of coronary artery disease. The results demonstrated no benefit of the treatment on the primary endpoint or components of the primary. During the conduct of the trial there were no major safety concerns.

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