Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)

Introduction The clinical significance of subsegmental pulmonary embolism (SSPE) is currently unclear. Although growing evidence from observational studies suggests that withholding anticoagulant treatment may be a safe option in selected patients with isolated SSPE, most patients with this conditio...

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Main Authors: Marc Carrier, Christine Baumgartner, Drahomir Aujesky, Menno V Huisman, Frederikus A Klok, Jeanne Moor, Marc Righini, Jürg-Hans Beer, Martina Peluso, Damiana Rakovic
Format: Article
Language:English
Published: BMJ Publishing Group 2020-11-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/11/e040151.full
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author Marc Carrier
Christine Baumgartner
Drahomir Aujesky
Menno V Huisman
Frederikus A Klok
Jeanne Moor
Marc Righini
Jürg-Hans Beer
Martina Peluso
Damiana Rakovic
author_facet Marc Carrier
Christine Baumgartner
Drahomir Aujesky
Menno V Huisman
Frederikus A Klok
Jeanne Moor
Marc Righini
Jürg-Hans Beer
Martina Peluso
Damiana Rakovic
author_sort Marc Carrier
collection DOAJ
description Introduction The clinical significance of subsegmental pulmonary embolism (SSPE) is currently unclear. Although growing evidence from observational studies suggests that withholding anticoagulant treatment may be a safe option in selected patients with isolated SSPE, most patients with this condition receive anticoagulant treatment, which is associated with a 90-day risk of recurrent venous thromboembolism (VTE) of 0.8% and major bleeding of up to 5%. Given the ongoing controversy concerning the risk-benefit ratio of anticoagulation for isolated SSPE and the lack of evidence from randomised-controlled studies, the aim of this clinical trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE.Methods and analysis SAFE-SSPE (Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism, a multicentre randomised placebo-controlled non-inferiority trial) is an international, multicentre, placebo-controlled, double-blind, parallel-group non-inferiority trial conducted in Switzerland, the Netherlands and Canada. Low-risk patients with isolated SSPE are randomised to receive clinical surveillance with either placebo (no anticoagulation) or anticoagulant treatment with rivaroxaban. All patients undergo bilateral whole-leg compression ultrasonography to exclude concomitant deep vein thrombosis before enrolment. Patients are followed for 90 days. The primary outcome is symptomatic recurrent VTE (efficacy). The secondary outcomes include clinically significant bleeding and all-cause mortality (safety). The ancillary outcomes are health-related quality of life, functional status and medical resource utilisation.Ethics and dissemination The local ethics committees in Switzerland have approved this protocol. Submission to the Ethical Committees in the Netherlands and Canada is underway. The results of this trial will be published in a peer-reviewed journal.Trial registration number NCT04263038.
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spelling doaj-art-a19c0f9974404c58b6bb50ca3f0c32ad2024-11-26T03:15:11ZengBMJ Publishing GroupBMJ Open2044-60552020-11-01101110.1136/bmjopen-2020-040151Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)Marc Carrier0Christine Baumgartner1Drahomir Aujesky2Menno V Huisman3Frederikus A Klok4Jeanne Moor5Marc Righini6Jürg-Hans Beer7Martina Peluso8Damiana Rakovic9Department of Clinical Epidemiology, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada1 Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland1 Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment of Thrombosis and Hemostasis, Leiden University Medical Centre, Leiden, The NetherlandsDepartment of Medicine-Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Zuid-Holland, The NetherlandsInstitute of Primary Health Care, University of Bern, Bern, Switzerland2 University of Geneva, Switzerland, Geneva, SwitzerlandDepartment of Medicine, Baden Cantonal Hospital, Baden, SwitzerlandDepartment of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandIntroduction The clinical significance of subsegmental pulmonary embolism (SSPE) is currently unclear. Although growing evidence from observational studies suggests that withholding anticoagulant treatment may be a safe option in selected patients with isolated SSPE, most patients with this condition receive anticoagulant treatment, which is associated with a 90-day risk of recurrent venous thromboembolism (VTE) of 0.8% and major bleeding of up to 5%. Given the ongoing controversy concerning the risk-benefit ratio of anticoagulation for isolated SSPE and the lack of evidence from randomised-controlled studies, the aim of this clinical trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation in low-risk patients with isolated SSPE.Methods and analysis SAFE-SSPE (Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism, a multicentre randomised placebo-controlled non-inferiority trial) is an international, multicentre, placebo-controlled, double-blind, parallel-group non-inferiority trial conducted in Switzerland, the Netherlands and Canada. Low-risk patients with isolated SSPE are randomised to receive clinical surveillance with either placebo (no anticoagulation) or anticoagulant treatment with rivaroxaban. All patients undergo bilateral whole-leg compression ultrasonography to exclude concomitant deep vein thrombosis before enrolment. Patients are followed for 90 days. The primary outcome is symptomatic recurrent VTE (efficacy). The secondary outcomes include clinically significant bleeding and all-cause mortality (safety). The ancillary outcomes are health-related quality of life, functional status and medical resource utilisation.Ethics and dissemination The local ethics committees in Switzerland have approved this protocol. Submission to the Ethical Committees in the Netherlands and Canada is underway. The results of this trial will be published in a peer-reviewed journal.Trial registration number NCT04263038.https://bmjopen.bmj.com/content/10/11/e040151.full
spellingShingle Marc Carrier
Christine Baumgartner
Drahomir Aujesky
Menno V Huisman
Frederikus A Klok
Jeanne Moor
Marc Righini
Jürg-Hans Beer
Martina Peluso
Damiana Rakovic
Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)
BMJ Open
title Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)
title_full Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)
title_fullStr Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)
title_full_unstemmed Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)
title_short Clinical Surveillance vs. Anticoagulation For low-risk patiEnts with isolated SubSegmental Pulmonary Embolism: protocol for a multicentre randomised placebo-controlled non-inferiority trial (SAFE-SSPE)
title_sort clinical surveillance vs anticoagulation for low risk patients with isolated subsegmental pulmonary embolism protocol for a multicentre randomised placebo controlled non inferiority trial safe sspe
url https://bmjopen.bmj.com/content/10/11/e040151.full
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