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

Stefano Barco, Irene Schmidtmann, Walter Ageno, Rupert M. Bauersachs, Cecilia Becattini, Enrico Bernardi, Jan Beyer-Westendorf, Luca Bonacchini, Johannes Brachmann, Michael Christ, Michael Czihal, Daniel Duerschmied, Klaus Empen, Christine Espinola-Klein, Joachim H. Ficker, Cândida Fonseca, Sabine Genth-Zotz, David Jiménez, Veli Pekka Harjola, Matthias Held & 14 others Lorenzo Iogna Prat, Tobias J. Lange, Athanasios Manolis, Andreas Meyer, Pirjo Mustonen, Ursula Rauch-Kroehnert, Pedro Ruiz-Artacho, Sebastian Schellong, Martin Schwaiblmair, Raoul Stahrenberg, Peter E. Westerweel, Philipp S. Wild, Stavros V. Konstantinides, Mareike Lankeit

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)509-518
Number of pages10
JournalEuropean Heart Journal
Volume41
Issue number4
DOIs
Publication statusPublished - 21 Jan 2020

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Pulmonary Embolism
Clinical Trials
Venous Thromboembolism
Right Ventricular Dysfunction
Therapeutics
Patient Safety
Patient Selection
Comorbidity
Length of Stay
Thrombosis
Hemodynamics
Research Personnel
Factor Xa Inhibitors
Rivaroxaban
Confidence Intervals
Hemorrhage
Safety
Recurrence
Population
Neoplasms

Keywords

  • Home treatment
  • Management trial
  • Pulmonary embolism
  • Right ventricular dysfunction
  • Risk stratification
  • Rivaroxaban

Cite this

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. / 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. In: European Heart Journal. 2020 ; Vol. 41, No. 4. pp. 509-518.
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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.",
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author = "Stefano Barco and Irene Schmidtmann and Walter Ageno and Bauersachs, {Rupert M.} and Cecilia Becattini and Enrico Bernardi and Jan Beyer-Westendorf and Luca Bonacchini and Johannes Brachmann and Michael Christ and Michael Czihal and Daniel Duerschmied and Klaus Empen and Christine Espinola-Klein and Ficker, {Joachim H.} and C{\^a}ndida Fonseca and Sabine Genth-Zotz and David Jim{\'e}nez and Harjola, {Veli Pekka} and Matthias Held and {Iogna Prat}, Lorenzo and Lange, {Tobias J.} and Athanasios Manolis and Andreas Meyer and Pirjo Mustonen and Ursula Rauch-Kroehnert and Pedro Ruiz-Artacho and Sebastian Schellong and Martin Schwaiblmair and Raoul Stahrenberg and Westerweel, {Peter E.} and Wild, {Philipp S.} and Konstantinides, {Stavros V.} and Mareike Lankeit",
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Barco, S, Schmidtmann, I, Ageno, W, Bauersachs, RM, Becattini, C, Bernardi, E, Beyer-Westendorf, J, Bonacchini, L, Brachmann, J, Christ, M, Czihal, M, Duerschmied, D, Empen, K, Espinola-Klein, C, Ficker, JH, Fonseca, C, Genth-Zotz, S, Jiménez, D, Harjola, VP, Held, M, Iogna Prat, L, Lange, TJ, Manolis, A, Meyer, A, Mustonen, P, Rauch-Kroehnert, U, Ruiz-Artacho, P, Schellong, S, Schwaiblmair, M, Stahrenberg, R, Westerweel, PE, Wild, PS, Konstantinides, SV & Lankeit, M 2020, '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', European Heart Journal, vol. 41, no. 4, pp. 509-518. https://doi.org/10.1093/eurheartj/ehz367

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. / 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.

In: European Heart Journal, Vol. 41, No. 4, 21.01.2020, p. 509-518.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban

T2 - an international multicentre single-arm clinical trial

AU - Barco, Stefano

AU - Schmidtmann, Irene

AU - Ageno, Walter

AU - Bauersachs, Rupert M.

AU - Becattini, Cecilia

AU - Bernardi, Enrico

AU - Beyer-Westendorf, Jan

AU - Bonacchini, Luca

AU - Brachmann, Johannes

AU - Christ, Michael

AU - Czihal, Michael

AU - Duerschmied, Daniel

AU - Empen, Klaus

AU - Espinola-Klein, Christine

AU - Ficker, Joachim H.

AU - Fonseca, Cândida

AU - Genth-Zotz, Sabine

AU - Jiménez, David

AU - Harjola, Veli Pekka

AU - Held, Matthias

AU - Iogna Prat, Lorenzo

AU - Lange, Tobias J.

AU - Manolis, Athanasios

AU - Meyer, Andreas

AU - Mustonen, Pirjo

AU - Rauch-Kroehnert, Ursula

AU - Ruiz-Artacho, Pedro

AU - Schellong, Sebastian

AU - Schwaiblmair, Martin

AU - Stahrenberg, Raoul

AU - Westerweel, Peter E.

AU - Wild, Philipp S.

AU - Konstantinides, Stavros V.

AU - Lankeit, Mareike

PY - 2020/1/21

Y1 - 2020/1/21

N2 - 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.

AB - 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.

KW - Home treatment

KW - Management trial

KW - Pulmonary embolism

KW - Right ventricular dysfunction

KW - Risk stratification

KW - Rivaroxaban

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U2 - 10.1093/eurheartj/ehz367

DO - 10.1093/eurheartj/ehz367

M3 - Article

VL - 41

SP - 509

EP - 518

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668x

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