Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial
Authors: Barco Stefano , Schmidtmann Irene , Ageno Walter , Bauersachs Rupert M , Becattini Cecilia , Bernardi Enrico , Beyer-Westendorf Jan , Bonacchini Luca , Brachmann Johannes , Christ Michael , Czihal Michael , Duerschmied Daniel , Empen Klaus , Espinola-Klein Christine , Ficker Joachim H , Fonseca Cândida , Genth-Zotz Sabine , Jiménez David , Harjola Veli-Pekka , Held Matthias , Iogna Prat Lorenzo , Lange Tobias J , Manolis Athanasios , Meyer Andreas , Mustonen Pirjo , Rauch-Kroehnert Ursula , Ruiz-Artacho Pedro , Schellong Sebastian , Schwaiblmair Martin , Stahrenberg Raoul , Westerweel Peter E , Wild Philipp S , Konstantinides Stavros V , Lankeit Mareike ,   HoT-PE Investigators, Konstantinides Stavros V , Bauersachs Rupert Martin , Bode Christoph , Christ Michael , Espinola-Klein Christine , Geibel Annette , Lankeit Mareike , Pfeifer Michael , Schellong Sebastian , Wild Philipp S , Binder Harald , Quitzau Kurt , Martin Nadine , Becker Dorothea , Barco Stefano , Schmidtmann Irene , Anusic Toni , Schwaiblmair Martin , Rauch-Kröhnert Ursula , Möckel Martin , Brachmann Johannes , Beyer-Westendorf Jan , Duerschmied Daniel , Blaschke Sabine , Hoeper Marius M , Giannitis Evangelos , Empen Klaus , Schmiedel Rainer , Hoffman Ulrich , Akin Ibrahim , Meyer Andreas , Genth-Zotz Sabine , Ficker Joachim , Geisler Tobias , Held Matthias , Becattini Cecilia , Cimini Ludovica , Walter Ageno Jörg Herold , Sbrojavacca Rodolfo , Bernardi Enrico , Bettoni Giuseppe , Cosentini Roberto , Moscatelli Paolo , Nitti Cinzia , Pazzaglia Maria , Pesavento Raffaele , Ascani Alessandra , Cortellaro Francesca , Montano Nicola , Westerweel Peter E , Ruiz-Artacho Pedro , Jiménez David , Ballaz-Quincoces Aitor , Reyes Raquel Lopez , Otero Remedios , Fonseca Candida , Judas Tiago , Araujo Inês , Batista Sergio , Goncalves Fabienne , Harjola Veli-Pekka , Mustonen Pirjo , Hahalis Georgios , Manginas Athanassios , Gougoulianis Konstantinos , Manolis Athanasios , Czihal Michael , Lange Tobias J , Stahrenberg Raoul , Meinertz Thomas , Huisman Menno V , Prandoni Paolo , Lehmacher Walter , Gorbulev Stanislav , Kronfeld Kai 
Published: May 2019

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 (&lt;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.