CLOSE: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design

Jean-Louis Mas , Geneviève Derumeaux (1) , Pierre Amarenco (2, 3) , Caroline Arquizan , Pierre Aubry (3) , Martine Barthelet , Bernard Bertrand , Eric Brochet (3) , Laure Cabanes , Erwan Donal (4, 5, 6) , Jean-Luc Dubois-Randé (7, 1) , Isabelle Durand-Zaleski , Laura Ernande , Gérard Finet (8) , Alain Fraisse (9) , Maurice Giroud (10) , Patrice Guerin (11) , Gilbert Habib (12, 13) , Jean-Michel Juliard (3) , Didier Leys (14) , Michel Lievre (15) , Jean-René Lusson (16, 17) , François Marçon (18) , Patrick Michel , Thierry Moulin , Francois Mounier-Vehier , Luc Pierard (19) , Christophe Piot (20) , Christian Rey , Gilles Rodier , Raymond Roudaut , Jean-Marc Schleich (5, 21) , Emmanuel Teiger (22, 1, 7) , Guillaume Turc (23) , Fabrice Vuillier , Christian Weimar (24) , France Woimant (25, 26) , Gilles Chatellier (27, 28)

1 IMRB - Institut Mondor de Recherche Biomédicale
2 Hôpital Bichat - Claude Bernard
3 LVTS (UMR_S_1148 / U1148) - Laboratoire de Recherche Vasculaire Translationnelle
4 CIC-IT Rennes
5 LTSI - Laboratoire Traitement du Signal et de l'Image
6 CIC - Centre d'Investigation Clinique [Rennes]
7 Service de cardiologie
8 Hôpital Louis Pradel [CHU - HCL]
9 AMU - Aix Marseille Université
10 Service de Neurologie générale, vasculaire et dégénérative (CHU de Dijon)
11 ITX-lab - Unité de recherche de l'institut du thorax
12 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
13 Service de cardiologie
14 TCDV - Troubles cognitifs dégénératifs et vasculaires - U 1171
15 Evaluation et modélisation des effets thérapeutiques
16 CHU Gabriel Montpied [Clermont-Ferrand]
17 ISIT - Image Science for Interventional Techniques
18 Service de Cardiologie Infantile [CHRU Nancy]
19 GIGA-Research - Groupe Interdisciplinaire de Génoprotéomique Appliquée
20 Cardiologie interventionnelle [Montpellier]
21 Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes]
22 CHU Henri Mondor - Département de physiologie
23 ENSCR - Ecole Nationale Supérieure de Chimie de Rennes
24 Department of Neurology and Stroke Center
25 Service de neurologie [Univ. Paris VII]
26 CNR wilson - Centre National de Référence pour la maladie de Wilson
27 Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques [CHU HEGP]
28 HEGP - Hôpital Européen Georges Pompidou [APHP]

Rationale Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale, oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke Aim To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke or retinal ischaemia. Sample size Six hundred and sixty-four patients were included in the study. Methods and design CLOSE is an academic-driven, multicentre, randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. The trial has been registered with Clinical Trials Register (Clinicaltrials.gov, NCT00562289). Patient recruitment started in December 2007. Patient follow-up will continue until December 2016. Expected mean follow-up=5.6 years. Study outcomes The primary efficacy outcome is the occurrence of fatal or nonfatal stroke. Safety outcomes include fatal, life-threatening or major procedure- or device-related complications and fatal, life-threatening or major haemorrhagic complications. Discussion CLOSE is the first specifically designed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke.

Keywords: medical therapy; transient ischemic attack; trials; percutaneous closure; paradoxical embolism; events; guidelines; cryptogenic stroke; metaanalysis; accuracy

Domains: Life Sciences [q-bio]

Jean-Louis Mas, Geneviève Derumeaux, Pierre Amarenco, Caroline Arquizan, Pierre Aubry, et al.. CLOSE: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design. International Journal of Stroke, 2016, 11 (6), pp.724--732. ⟨10.1177/1747493016643551⟩. ⟨hal-01414463⟩