Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism

NCT ID: NCT04263038

Last Updated: 2025-05-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

276 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-15

Study Completion Date

2026-05-31

Brief Summary

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The clinical significance of pulmonary embolism (PE) limited to the subsegmental pulmonary arteries, so called isolated subsegmental pulmonary embolism (SSPE), remains controversial. Whether isolated SSPE represents "true" PE, a clinically more benign form of PE, a physiologic lung clearing process, or a false positive result (artifact) is currently unclear and hence, whether patients with isolated SSPE benefit from anticoagulant treatment is uncertain. Despite growing evidence from observational studies that withholding anticoagulation may be a safe option in selected patients with isolated SSPE (i.e., those without concomitant deep vein thrombosis, cancer, etc.), most patients with isolated SSPE receive anticoagulant treatment, which is associated with an increased risk of bleeding. The overall objective of the randomized controlled SAFE-SSPE trial is to evaluate the efficacy and safety of clinical surveillance without anticoagulation compared to anticoagulation treatment in low-risk patients with isolated SSPE.

Detailed Description

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Conditions

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Pulmonary Embolism Embolism Embolism and Thrombosis Lung Diseases Cardiovascular Diseases Respiratory Tract Diseases Venous Thromboembolism Anticoagulant-induced Bleeding Bleeding

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Anticoagulation

Patients in the anticoagulation group will receive rivaroxaban 15 mg twice daily for the first 21 days, followed by 20 mg once daily for an overall treatment duration of 90 days.

Group Type ACTIVE_COMPARATOR

Rivaroxaban

Intervention Type DRUG

Anticoagulation

No anticoagulation

Patients in the group without anticoagulation will receive placebo twice daily for the first 21 days, followed by one tablet daily for an overall treatment duration of 90 days.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Study drug without active agent

Interventions

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Rivaroxaban

Anticoagulation

Intervention Type DRUG

Placebo

Study drug without active agent

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Informed Consent as documented by signature
2. Age ≥18 years
3. Objective diagnosis of symptomatic or asymptomatic isolated SSPE

Exclusion Criteria

1. Presence of leg deep vein thrombosis (DVT) or upper extremity DVT (subclavian vein or above)
2. Active cancer, defined as cancer treated with surgery, chemotherapy, radiotherapy, or palliative care during the last 6 months
3. ≥1 prior episode of unprovoked VTE (absence of a transient or permanent risk factor)
4. Clinical instability (systolic blood pressure \<100 mm Hg or arterial Oxygen saturation \<92% at ambient air) at the time of presentation
5. Active bleeding or at high risk of bleeding
6. Severe renal failure (creatinine clearance \<30ml/min)
7. Severe liver insufficiency (Child-Pugh B or C)
8. Concomitant use of strong CYP3A4 inhibitors or strong CYP3A4 inducers
9. Known hypersensitivity to rivaroxaban
10. Need for therapeutic anticoagulation for another reason
11. Therapeutic anticoagulation for \>72 hours for any reason at the time of screening
12. Hospitalized for \>72 hours prior to the diagnosis of isolated SSP (hospital-acquired VTE)
13. Known pregnancy or breast feeding (pregnancy test to be performed for women of childbearing potential)
14. Lack of safe contraception in women of childbearing potential
15. Refusal or inability to provide informed consent
16. Prior enrolment in this trial
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Bern

OTHER

Sponsor Role collaborator

Schweizerischer Nationalfonds

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

The Ottawa Hospital

OTHER

Sponsor Role collaborator

Bayer

INDUSTRY

Sponsor Role collaborator

Drahomir Aujesky

OTHER

Sponsor Role lead

Responsible Party

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Drahomir Aujesky

Prof. Dr., MD, MSc

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Drahomir Aujesky, Prof. MD MSc

Role: STUDY_DIRECTOR

Inselspital, Bern University Hospital, University of Bern

Locations

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Centre hospitalier universitaire de Liege

Liège, , Belgium

Site Status NOT_YET_RECRUITING

Cliniques Universitaires Saint-Luc

Woluwe-Saint-Lambert, , Belgium

Site Status RECRUITING

The Ottawa Hospital

Ottawa, , Canada

Site Status RECRUITING

Hôpital Bicêtre - APHP

Le Kremlin-Bicêtre, Le Kremlin-Bicêtre, France

Site Status RECRUITING

Centre Hospitalier Regional Et Universitaire De Brest

Brest, , France

Site Status RECRUITING

CHU Gabriel-Montpied

Clermont-Ferrand, , France

Site Status RECRUITING

Centre Hospitalier Universitaire De Dijon

Dijon, , France

Site Status RECRUITING

Hospital Edouard Herriot

Lyon, , France

Site Status RECRUITING

CHU De Rouen

Rouen, , France

Site Status RECRUITING

CHU ST Etienne - Hôpital Nord

Saint-Priest-en-Jarez, , France

Site Status RECRUITING

Albert Schweitzer Ziekenhuis Dordrecht

Dordrecht, , Netherlands

Site Status RECRUITING

Medisch Spectrum Twente

Enschede, , Netherlands

Site Status RECRUITING

Leiden University Medical Center

Leiden, , Netherlands

Site Status RECRUITING

Erasmus Universitair Medisch Centrum

Rotterdam, , Netherlands

Site Status RECRUITING

Haaglanden Medisch Centrum

The Hague, , Netherlands

Site Status WITHDRAWN

Isala Klinieken Zwolle

Zwolle, , Netherlands

Site Status RECRUITING

Cantonal Hospital of Liestal

Liestal, Basel, Switzerland

Site Status RECRUITING

Cantonal Hospital of Aarau

Aarau, Canton of Aargau, Switzerland

Site Status RECRUITING

University Hospital Inselspital

Bern, Canton of Bern, Switzerland

Site Status RECRUITING

Hospital of Bienne

Biel/Bienne, Canton of Bern, Switzerland

Site Status RECRUITING

Cantonal Hospital of Fribourg

Fribourg, Canton of Fribourg, Switzerland

Site Status RECRUITING

Cantonal Hospital of Lucerne

Lucerne, Canton of Lucerne, Switzerland

Site Status WITHDRAWN

Cantonal Hospital of Olten

Olten, Canton of Solothurn, Switzerland

Site Status WITHDRAWN

Cantonal Hospital of St. Gallen

Sankt Gallen, Canton of St. Gallen, Switzerland

Site Status RECRUITING

University Hospital of Lausanne

Lausanne, Canton of Vaud, Switzerland

Site Status RECRUITING

Hospital of Nyon

Nyon, Canton of Vaud, Switzerland

Site Status WITHDRAWN

Cantonal Hospital of Winterthur

Winterthur, Canton of Zurich, Switzerland

Site Status RECRUITING

Triemli Hospital

Zurich, Canton of Zurich, Switzerland

Site Status RECRUITING

University Hospital Zürich

Zurich, Canton of Zurich, Switzerland

Site Status RECRUITING

Cantonal Hospital of Frauenfeld

Frauenfeld, Thurgau, Switzerland

Site Status RECRUITING

Hospital of Sion

Sion, Valais, Switzerland

Site Status WITHDRAWN

Cantonal Hospital of Uri

Altdorf, , Switzerland

Site Status WITHDRAWN

Cantonal Hospital of Baden

Baden, , Switzerland

Site Status RECRUITING

University Hospital of Basel

Basel, , Switzerland

Site Status RECRUITING

Tiefenau Hospital

Bern, , Switzerland

Site Status COMPLETED

Regional Hospital of Emmental

Burgdorf, , Switzerland

Site Status RECRUITING

Hospital of Delémont

Delémont, , Switzerland

Site Status RECRUITING

Geneva University Hospital

Geneva, , Switzerland

Site Status RECRUITING

Hospital of Neuchâtel

Neuchâtel, , Switzerland

Site Status RECRUITING

Countries

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Belgium Canada France Netherlands Switzerland

Central Contacts

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Drahomir Aujesky, Prof. MD MSc

Role: CONTACT

+41 31 632 88 84

Tobias Tritschler, Dr. MD MSc

Role: CONTACT

+41 31 63 2 01 46

Facility Contacts

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Raphaelle Lopez Iglesias, MD

Role: primary

Andrea Penaloza Baeza, Prof., MD

Role: primary

Marc Carrier, Prof. MD MSc

Role: primary

Mitja Jevnikar, Dr.

Role: primary

0145213487

Francis Couturaud, Prof. MD

Role: primary

Jeannot Schmidt, Prof., MD

Role: primary

Nicolas Falvo, MD

Role: primary

Judith Catella, MD

Role: primary

Sébastien Miranda, MD

Role: primary

Laurent Bertoletti, Prof., MD

Role: primary

P.E. Westerweel, MD

Role: primary

H.P.A.A. van Veen, MD

Role: primary

F. A. Klok, Prof. MD PhD

Role: primary

M. Kruip, MD

Role: primary

M. F. Boosma, MD

Role: primary

Jörg Leuppi, Prof. MD PhD

Role: primary

Philippe Schütz, Prof. MD MPH

Role: primary

Drahomir Aujesky, Prof. MD MSc

Role: primary

Daniel Genné, Prof. MD

Role: primary

Julien Vaucher, Prof. MD

Role: primary

Claudio S. Rüegg, MD

Role: primary

Marie Méan, MD MER

Role: primary

Bettina Portocarrero, MD

Role: primary

Lars Huber, PD MD

Role: primary

Ksenija Slankamenac, PD, MD, PhD

Role: primary

Andreas Kistler, PD MD

Role: primary

Maria Wertli, Prof. MD

Role: primary

Roland Bingisser, Prof. MD

Role: primary

Robert Escher, PD Dr. MD

Role: primary

Hervé Duplain, PD Dr. MD

Role: primary

Marc Righini, Prof. MD

Role: primary

Jacques Donzé, Prof. MD MSc

Role: primary

References

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Baumgartner C, Klok FA, Carrier M, Limacher A, Moor J, Righini M, Beer JH, Peluso M, Rakovic D, Huisman MV, Aujesky D. 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. 2020 Nov 19;10(11):e040151. doi: 10.1136/bmjopen-2020-040151.

Reference Type DERIVED
PMID: 33444199 (View on PubMed)

Other Identifiers

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2019-02297

Identifier Type: -

Identifier Source: org_study_id

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