Stefano Barco1, Irene Schmidtmann2, Walter Ageno3, Rupert M Bauersachs4, Cecilia Becattini5, Enrico Bernardi6, Jan Beyer-Westendorf7,8, Luca Bonacchini9, Johannes Brachmann10, Michael Christ11, Michael Czihal12, Daniel Duerschmied13, Klaus Empen14, Christine Espinola-Klein1,15, Joachim H Ficker16, Cândida Fonseca17, Sabine Genth-Zotz18, David Jiménez19, Veli-Pekka Harjola20, Matthias Held21, Lorenzo Iogna Prat22, Tobias J Lange23, Athanasios Manolis24, Andreas Meyer25, Pirjo Mustonen26, Ursula Rauch-Kroehnert27, Pedro Ruiz-Artacho28,29, Sebastian Schellong30, Martin Schwaiblmair31, Raoul Stahrenberg32, Peter E Westerweel33, Philipp S Wild1,34,35, Stavros V Konstantinides1,36, Mareike Lankeit1,37,38. 1. Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, Building 403, 55131 Mainz, Germany. 2. Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center Mainz, Obere Zahlbacher Strasse 69, 55131 Mainz, Germany. 3. Department of Medicine and Surgery, Research Center on Thromboembolic Diseases and Antithrombotic Therapies, University of Insubria, Viale Luigi Borri 57, 21100 Varese, Italy. 4. Department of Vascular Medicine, Klinikum Darmstadt, Grafenstrasse 9, 64283 Darmstadt, Germany. 5. Internal and Cardiovascular Medicine - Stroke Unit, University of Perugia, Via G. Dottori 1, 06129 Perugia, Italy. 6. Department of Emergency Medicine, ULSS n.7, Via Brigata Bisagno 4, 31015 Conegliano (Treviso), Italy. 7. Thrombosis Research Unit, Division of Hematology, Department of Medicine I, University Hospital "Carl Gustav Carus", Fetscherstrasse 74, 01307 Dresden, Germany. 8. Kings Thrombosis Service, Department of Hematology, Kings College London, Denmark Hill, Brixton, SE5 9RS, London, UK. 9. S.C. Medicina d'Urgenza e Pronto Soccorso, ASST Grande Ospedale Metropolitano Niguarda, Piazza dell'Ospedale Maggiore 3, 20162 Milano, Italy. 10. II Medical Department, Coburg Hospital, Ketschendorfer Strasse 33, 96450 Coburg, Germany. 11. Emergency Care (Notfallzentrum), Luzerner Kantonsspital, 6000 Luzern, Switzerland. 12. Division of Vascular Medicine, Hospital of the Ludwig-Maximilians-University, Georgenstrasse 5, 80799 Munich, Germany. 13. Department of Cardiology and Angiology I, Heart Center, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany. 14. Department of Internal Medicine, University Medical Center, Fleischmannstrasse 6, 17489 Greifswald, Germany. 15. Center for Cardiology, Cardiology 1, University Medical Center of the Johannes Gutenberg-University, Langenbeckstrasse 1, 55131 Mainz, Germany. 16. Department of Respiratory Medicine, Nuremberg General Hospital/Paracelsus Medical University, Prof.-Ernst-Nathan-Strasse 1, 90419 Nuremberg, Germany. 17. Department of Internal Medicine, Hospital S. Francisco Xavier/CHLO, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisbon, Portugal. 18. Department of Internal Medicine I, Katholisches Klinikum Mainz, An der Goldrube 11, 55131 Mainz, Germany. 19. Respiratory Department, Ramón y Cajal Hospital, Universidad de Alcala, IRYCIS, Ctra. Colmenar Viejo, km. 9, 100, 28034 Madrid, Spain. 20. Emergency Medicine, University of Helsinki, Department of Emergency Medicine and Services, Helsinki University Hospital, Tukholmankatu 8A, 00290 Helsinki, Finland. 21. Department of Internal Medicine, Medical Mission Hospital, Academic Teaching Hospital of the Julius-Maximilian University of Wuerzburg, Josef-Schneider-Strasse 2, 97080 Wuerzburg, Germany. 22. Department of Emergency Medicine, Santa Maria della Misericordia Hospital, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy. 23. Department of Internal Medicine II, Division of Pneumology, University Medical Center Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. 24. Department of Cardiology, General Hospital 'Asklepeion Voulas', Leof. Vasileos Pavlou 1, 166 73 Athens, Greece. 25. Kliniken Maria Hilf, Klinik für Pneumologie, Krankenhaus St. Franziskus, Viersener Str. 450, 41063 Mönchengladbach, Germany. 26. Department of Medicine, Keski-Suomi Central Hospital and University of Jyväskylä, Keskussairaalantie 19, 40620 Jyväskylä, Finland. 27. Department of Cardiology, University Heart Center Berlin, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; German Center for Cardiovascular Research (DZHK), Berlin, Germany. 28. Emergency Department, Clinico San Carlos Hospital, IdISSC, alle del Prof Martín Lagos, s/n, 28040 Madrid, Spain. 29. Internal Medicine Department, University Clinic of Navarra, Calle Marquesado de Sta. Marta 1, 28027 Madrid, Spain. 30. Vascular Center, Municipal Hospital of Dresden-Friedrichstadt, Friedrichstraße 41, 01067 Dresden, Germany. 31. Department of Cardiology, Respiratory Medicine and Intensive Care, Klinikum Augsburg, Ludwig-Maximilians-University Munich, Stenglinstrasse 2, 86156 Munich, Germany. 32. Helios Albert-Schweitzer-Klinik, Albert-Schweitzer-Weg 1, 37154 Northeim, Germany. 33. Department of Internal Medicine, Albert Schweitzer Hospital, Albert Schweitzerplaats 25, 3318 AT Dordrecht, The Netherlands. 34. German Center for Cardiovascular Research (DZHK), Partner Site Rhine Main, Mainz, Germany. 35. Center for Cardiology, Preventive Cardiology and Preventive Medicine, University Medical Center of the Johannes Gutenberg University, Langenbeckstrasse 1, 55131 Mainz, Germany. 36. Department of Cardiology, Democritus University of Thrace, 68100 Alexandroupolis, Greece. 37. Department of Internal Medicine and Cardiology, Campus Virchow Klinikum, Charité - University Medicine Berlin, Augustenburgerplatz 1, 13353 Berlin, Germany. 38. Clinic of Cardiology and Pneumology, Heart Center, University Medical Center Goettingen, Robert-Koch-Strasse 40, 37075 Goettingen, Germany.
Abstract
AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.
RCT Entities:
AIMS: To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. METHODS AND RESULTS: We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was symptomatic recurrent venous thromboembolism (VTE) or PE-related death within 3 months of enrolment. An interim analysis was planned after the first 525 patients, with prespecified early termination of the study if the null hypothesis could be rejected at the level of α = 0.004 (<6 primary outcome events). From May 2014 through June 2018, consecutive patients were enrolled in seven countries. Of the 525 patients included in the interim analysis, three (0.6%; one-sided upper 99.6% confidence interval 2.1%) suffered symptomatic non-fatal VTE recurrence, a number sufficiently low to fulfil the condition for early termination of the trial. Major bleeding occurred in 6 (1.2%) of the 519 patients comprising the safety population. There were two cancer-related deaths (0.4%). CONCLUSION: Early discharge and home treatment with rivaroxaban is effective and safe in carefully selected patients with acute low-risk PE. The results of the present trial support the selection of appropriate patients for ambulatory treatment of PE.
Authors: Rasha Khatib; Stephanie Ross; Sean Alexander Kennedy; Ivan D Florez; Thomas L Ortel; Robby Nieuwlaat; Ignacio Neumann; Daniel M Witt; Sam Schulman; Veena Manja; Rebecca Beyth; Nathan P Clark; Wojtek Wiercioch; Holger J Schünemann; Yuqing Zhang Journal: Blood Adv Date: 2020-02-11
Authors: Behnood Bikdeli; Mahesh V Madhavan; David Jimenez; Taylor Chuich; Isaac Dreyfus; Elissa Driggin; Caroline Der Nigoghossian; Walter Ageno; Mohammad Madjid; Yutao Guo; Liang V Tang; Yu Hu; Jay Giri; Mary Cushman; Isabelle Quéré; Evangelos P Dimakakos; C Michael Gibson; Giuseppe Lippi; Emmanuel J Favaloro; Jawed Fareed; Joseph A Caprini; Alfonso J Tafur; John R Burton; Dominic P Francese; Elizabeth Y Wang; Anna Falanga; Claire McLintock; Beverley J Hunt; Alex C Spyropoulos; Geoffrey D Barnes; John W Eikelboom; Ido Weinberg; Sam Schulman; Marc Carrier; Gregory Piazza; Joshua A Beckman; P Gabriel Steg; Gregg W Stone; Stephan Rosenkranz; Samuel Z Goldhaber; Sahil A Parikh; Manuel Monreal; Harlan M Krumholz; Stavros V Konstantinides; Jeffrey I Weitz; Gregory Y H Lip Journal: J Am Coll Cardiol Date: 2020-04-17 Impact factor: 24.094