Robert G Hart1, Mukul Sharma1, Hardi Mundl2, Ashkan Shoamanesh1, Scott E Kasner3, Scott D Berkowitz4, Guillaume Pare1, Bodo Kirsch5, Janice Pogue6, Calin Pater7, Gary Peters8, Antoni Davalos9, Wilfried Lang10, Yongjun Wang11, Yilong Wang11, Luis Cunha12, Jens Eckstein13, Turgut Tatlisumak14, Nikolay Shamalov15, Robert Mikulik16, Pablo Lavados17, Graeme J Hankey18, Anna Czlonkowska19, Danilo Toni20, Sebastian F Ameriso21, Rubens J Gagliardi22, Pierre Amarenco23, Daniel Bereczki24, Shinichiro Uchiyama25, Arne Lindgren26, Matthias Endres27, Raf Brouns28, Byung-Woo Yoon29, George Ntaios30, Roland Veltkamp31, Keith W Muir32, Serefnur Ozturk33, Antonio Arauz34, Natan Bornstein35, Alan Bryer36, Martin J O'Donnell37, Jeffrey Weitz38, Frank Peacock39, Ellison Themeles40, Stuart J Connolly41. 1. Department of Medicine (Neurology), Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, Canada. 2. Bayer Pharma AG, Wuppertal, Germany. 3. Department of Neurology, University of Pennsylvania, Philadelphia, USA. 4. Bayer Healthcare Pharmaceuticals, Parsippany, USA. 5. Bayer Pharma AG, Berlin, Germany. 6. Department of Clinical Epidemiology and Biostatistics, Department of Medicine, Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, Canada. 7. Bayer Vital, Leverkusen, Germany. 8. Janssen Research and Development, LLC, Spring House, Pennsylvania, USA. 9. Department of Neurosciences, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. 10. Hospital St. John of God, Medical Faculty, Sigmund Freud University, Vienna, Austria. 11. Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. 12. Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal. 13. Department of Innere Medizin, Universitätsspital Basel, Basel, Switzerland. 14. Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. 15. Pirogov Russian National Research Medical University, Moscow, Russia. 16. International Clinical Research Center and Neurology Department, St. Anne's University Hospital, Brno, Czech Republic. 17. Clinica Alemana de Santiago, Universidad del Desarrollo, Universidad de Chile, Santiago, Chile. 18. School of Medicine and Pharmacology, University of Western Australia, Sir Charles Gairdner Hospital, Perth, Australia. 19. 2nd Department of Neurology, Institute of Psychiatry and Neurology, Medical University of Warsaw, Warsaw, Poland. 20. Department of Neurology and Psychiatry, "Sapienza" University of Rome, Rome, Italy. 21. Institute for Neurological Research, Fundacion para la Lucha contra las Enfermedades Neurologicas de la Infancia (FLENI), Buenos Aires, Argentina. 22. Irmandade da Santa Casa de Misericórdia de São Paulo, Sao Paulo, Brazil. 23. Department of Neurology, Bichat Hospital, Paris, France. 24. Department of Neurology, Semmelweis University, Budapest, Hungary. 25. Sanno Hospital and Sanno Medical Center, Tokyo, Japan. 26. Department of Clinical Sciences (Neurology), Department of Neurology and Rehabilitation Medicine, Skane University Hospital, Lund University, Lund, Sweden. 27. Klinik und Hochschulambulanz für Neurologie, Center for Stroke Research Berlin, Charité-Universitätsmedizin, Berlin, Germany. 28. Universitair Ziekenhuis Brussel, Brussels, Belgium. 29. Department of Neurology, Seoul National University Hospital, Seoul, Korea. 30. Department of Medicine, University of Thessaly, Larissa, Greece. 31. Imperial College London, London, UK. 32. Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK. 33. Department of Neurology, Selcuk University, Konya, Turkey. 34. Instituto Nacional de Neurologia y Neurocirugia, Mexico D.F., Mexico. 35. Tel-Aviv Medical Center, Tel-Aviv, Israel. 36. Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. 37. National University of Ireland, Galway, Ireland. 38. Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Canada. 39. Baylor College of Medicine, Houston, USA. 40. Population Health Research Institute, Hamilton, Canada. 41. Department of Medicine (Cardiology), Population Health Research Institute, McMaster University, Hamilton Health Sciences, Hamilton, Canada.
Abstract
BACKGROUND: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. MAIN HYPOTHESIS: In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. DESIGN: Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. SUMMARY: The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.
BACKGROUND: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. MAIN HYPOTHESIS: In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. DESIGN: Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. SUMMARY: The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.
Authors: Jin Myoung Seok; Seon Gyeong Kim; Ji Won Kim; Chin-Sang Chung; Gyeong-Moon Kim; Kwang Ho Lee; Oh Young Bang Journal: Ann Neurol Date: 2010-08 Impact factor: 10.422
Authors: Manesh R Patel; Kenneth W Mahaffey; Jyotsna Garg; Guohua Pan; Daniel E Singer; Werner Hacke; Günter Breithardt; Jonathan L Halperin; Graeme J Hankey; Jonathan P Piccini; Richard C Becker; Christopher C Nessel; John F Paolini; Scott D Berkowitz; Keith A A Fox; Robert M Califf Journal: N Engl J Med Date: 2011-08-10 Impact factor: 91.245
Authors: Ralph L Sacco; Shyam Prabhakaran; J L P Thompson; Amy Murphy; Robert R Sciacca; Bruce Levin; J-P Mohr Journal: Cerebrovasc Dis Date: 2006-03-27 Impact factor: 2.762
Authors: Marc I Chimowitz; Michael J Lynn; Harriet Howlett-Smith; Barney J Stern; Vicki S Hertzberg; Michael R Frankel; Steven R Levine; Seemant Chaturvedi; Scott E Kasner; Curtis G Benesch; Cathy A Sila; Tudor G Jovin; Jose G Romano Journal: N Engl J Med Date: 2005-03-31 Impact factor: 91.245
Authors: Stuart J Connolly; John Eikelboom; Campbell Joyner; Hans-Christoph Diener; Robert Hart; Sergey Golitsyn; Greg Flaker; Alvaro Avezum; Stefan H Hohnloser; Rafael Diaz; Mario Talajic; Jun Zhu; Prem Pais; Andrzej Budaj; Alexander Parkhomenko; Petr Jansky; Patrick Commerford; Ru San Tan; Kui-Hian Sim; Basil S Lewis; Walter Van Mieghem; Gregory Y H Lip; Jae Hyung Kim; Fernando Lanas-Zanetti; Antonio Gonzalez-Hermosillo; Antonio L Dans; Muhammad Munawar; Martin O'Donnell; John Lawrence; Gayle Lewis; Rizwan Afzal; Salim Yusuf Journal: N Engl J Med Date: 2011-02-10 Impact factor: 91.245
Authors: Ralph Weber; Michael Goertler; Jens Benemann; Hans Christoph Diener; Christian Weimar Journal: Cerebrovasc Dis Date: 2009-10-22 Impact factor: 2.762
Authors: M Haris U Usman; Lawrence A Notaro; Rangadham Nagarakanti; Eric Brahin; Scott Dessain; Edward Gracely; Michael D Ezekowitz Journal: Am J Cardiol Date: 2009-03-04 Impact factor: 2.778
Authors: Christopher Traenka; Henrik Gensicke; Sabine Schaedelin; Andreas Luft; Marcel Arnold; Patrik Michel; Georg Kägi; Timo Kahles; Christian H Nolte; Lars Kellert; Sverre Rosenbaum; Roman Sztaizel; Alex Brehm; Christoph Stippich; Marios Psychogios; Philippe Lyrer; Stefan T Engelter Journal: Eur Stroke J Date: 2020-06-29
Authors: Hans-Christoph Diener; J Donald Easton; Robert G Hart; Scott Kasner; Hooman Kamel; George Ntaios Journal: Nat Rev Neurol Date: 2022-05-10 Impact factor: 44.711
Authors: Paulina E Gąsiorek; Maciej Banach; Marek Maciejewski; Andrzej Głąbiński; Aleksandra Paduszyńska; Jacek Rysz; Agata Bielecka-Dąbrowa Journal: Cardiol J Date: 2018-05-02 Impact factor: 2.737
Authors: George Ntaios; Gregory Y H Lip; Konstantinos Vemmos; Eleni Koroboki; Efstathios Manios; Anastasia Vemmou; Ana Rodríguez-Campello; Elisa Cuadrado-Godia; Jaume Roquer; Valentina Arnao; Valeria Caso; Maurizio Paciaroni; Exuperio Diez-Tejedor; Blanca Fuentes; Josefa Pérez Lucas; Antonio Arauz; Sebastian F Ameriso; Lucía Pertierra; Maia Gómez-Schneider; Maximiliano A Hawkes; Fabio Bandini; Beatriz Chavarria Cano; Ana Maria Iglesias Mohedano; Andrés García Pastor; Antonio Gil-Núñez; Jukka Putaala; Turgut Tatlisumak; Miguel A Barboza; George Athanasakis; Fotios Gioulekas; Konstantinos Makaritsis; Vasileios Papavasileiou Journal: Neurology Date: 2017-07-07 Impact factor: 9.910
Authors: Mukul Sharma; Eric E Smith; Lesly A Pearce; Kanjana S Perera; Scott E Kasner; Byung-Woo Yoon; Sebastian F Ameriso; Josep Puig; Dorte Damgaard; Jochen B Fiebach; Keith W Muir; Roland C Veltkamp; Danilo S Toni; Nikolay Shamalov; Rubens J Gagliardi; Robert Mikulik; Stefan T Engelter; Daniel Bereczki; Martin J O'Donnell; Feryal Saad; Ashkan Shoamanesh; Scott D Berkowitz; Hardi Mundl; Robert G Hart Journal: Int J Stroke Date: 2021-11-18 Impact factor: 6.948
Authors: Morin Beyeler; Nebiyat F Belachew; Moritz Kielkopf; Enrique B Aleman; Alejandro Xavier León Betancourt; Kotryna Genceviciute; Christoph Kurmann; Lorenz Grunder; Barbara Birner; Thomas R Meinel; Adrian Scutelnic; Philipp Bücke; David J Seiffge; Tomas Dobrocky; Eike I Piechowiak; Sara Pilgram-Pastor; Heinrich P Mattle; Pasquale Mordasini; Marcel Arnold; Urs Fischer; Thomas Pabst; Jan Gralla; Martin D Berger; Simon Jung; Johannes Kaesmacher Journal: Front Neurol Date: 2022-07-14 Impact factor: 4.086