Study Design of the CLOSURE I Trial

Abstract

Background and Purpose-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. Study Design-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 Ն31 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.

Patent foramen ovale closure versus medical therapy after cryptogenic stroke: An updated meta-analysis of all randomized clinical trials

“…The first RCT (CLOSURE 1) [10,19] failed to demonstrate the benefit of PFO closure with the STARFlex device in preventing cryptogenic stroke over medical therapy alone. A similar result was obtained in the PC trial [11,20].…”

Patent Foramen Ovale May Be Causal for the First Stroke but Unrelated to Subsequent Ischemic Events

“…The only randomized controlled trial reported so far did not observe any difference between medical treatment and PFO closure in preventing recurrent stroke or TIA. 11 The reasons behind the lack of difference remain to be analyzed, though low recurrence rates in both treatment arms are no doubt a major challenge for this and for future trials.…”

The percutaneous closure of patent foramen ovale (PFO): Impact on the quality of life

“…In patients with cryptogenic stroke and PFO, the percutaneous closure treatment represents a possible and effective procedure and a possible alternative to the only antiplatelet or anticoagulant medical therapy conducted for a lifetime [7,8], even if the first randomized controlled trial, CLOSURE I,has not demonstrated the superiority of the percutaneous treatment against the medical therapy [9]. In our center the percutaneous technique was initiated relatively recently, however our results are encouraging.…”