Study design of the CLOSURE I Trial: 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 stroke or transient ischemic attack due to presumed paradoxical embolism through a patent foramen ovale.
OBJECTIVE
Some strokes of unknown etiology may be the result of a paradoxical embolism traversing through a nonfused foramen ovale (patent foramen ovale [PFO]). The utility of percutaneously placed devices for treatment of patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO is unknown. In addition, there are no clear data about the utility of medical interventions or other surgical procedures in this situation. Despite limited data, many patients are being treated with PFO closure devices. Thus, there is a strong need for clinical trials that test the potential efficacy of PFO occlusive devices in this situation. To address this gap in medical knowledge, we designed the CLOSURE I trial, a randomized, clinical trial comparing the use of a percutaneously placed PFO occlusive device and best medical therapy versus best medical therapy alone for prevention of recurrent ischemic neurologic symptoms among persons with TIA or ischemic stroke.


METHODS
This prospective, multicenter, randomized, controlled trial has finished enrollment. Two-year follow-up for all 910 patients is required. The primary end point is the 2-year incidence of stroke or TIA, all-cause mortality for the first 30 days, and neurologic mortality from ≥ 31 days of follow-up, as adjudicated by a panel of physicians who are unaware of treatment allocation. This article describes the rationale and study design of CLOSURE I.


CONCLUSIONS
This trial should provide information as to whether the STARFlex septal closure system is safe and more effective than best medical therapy alone in preventing recurrent stroke/TIA and mortality in patients with PFO and whether the STARFlex septal closure device can demonstrate superiority compared with best medical therapy alone. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00201461.
Department of Neurology, Neurological Institute-Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. Anthony.Furlan@UHhospitals.org
Anthony J
AJ
Furlan
Mark
M
Reisman
Joseph
J
Massaro
Laura
L
Mauri
Harold
H
Adams
Gregory W
GW
Albers
Robert
R
Felberg
Howard
H
Herrmann
Saibal
S
Kar
Michael
M
Landzberg
Albert
A
Raizner
Lawrence
L
Wechsler
D001778:Blood Coagulation Disorders / Q000097:blood / Q000150:complications; D019411:Clinical Laboratory Techniques; D017548:Echocardiography, Transesophageal; D023381:Endpoint Determination; D005500:Follow-Up Studies; D054092:Foramen Ovale, Patent / Q000150:complications*; D006801:Humans; D020766:Intracranial Embolism / Q000150:complications*; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000628:therapy*; D008881:Migraine Disorders / Q000150:complications; D011446:Prospective Studies; D012107:Research Design; D018401:Sample Size; D055502:Secondary Prevention; D015607:Stents / Q000009:adverse effects; D020521:Stroke / Q000209:etiology / Q000628:therapy*