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Pulmonary EmbolismPhase 4SAFE-SSPENCT04263038

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

A Phase 4 study testing Rivaroxaban in people with Pulmonary Embolism and Embolism, run by Drahomir Aujesky at 40 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The clinical significance of pulmonary embolism (PE) limited to the subsegmental pulmonary arteries, so called isolated subsegmental pulmonary embolism (SSPE), remains controversial. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Rivaroxaban
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
276 participants
Where
40 sitesin 5 countries
Study dates
15 May 2020to May 2028
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Informed Consent as documented by signature
  • Age ≥18 years
  • Objective diagnosis of symptomatic or asymptomatic isolated SSPE

Who cannot join

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

Trial locations and contacts

40 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Drahomir Aujesky, Prof. MD MSc contact

+41 31 632 88 84

SAFE-SSPE@insel.ch

Tobias Tritschler, Dr. MD MSc contact

+41 31 63 2 01 46

SAFE-SSPE@insel.ch

40 sites in 5 countries

Switzerland23 sites, 14 recruiting

  • Cantonal Hospital of Aarau

    Aarau, Canton of Aargau

    Philippe Schütz, Prof. MD MPH

    Philippe Schütz, Prof., MD, MPH

    Recruiting

  • Cantonal Hospital of Uri

    Altdorf

    Withdrawn

  • Cantonal Hospital of Baden

    Baden

    Maria Wertli, Prof. MD

    Maria Wertli, Prof., MD

    Recruiting

  • University Hospital of Basel

    Basel

    Roland Bingisser, Prof., MD

    Roland Bingisser, Prof., MD

    Recruiting

  • University Hospital Inselspital

    Bern, Canton of Bern, 3010

    Drahomir Aujesky, Prof. MD MSc

    Drahomir Aujesky, Prof., MD, MSc

    Recruiting

  • Tiefenau Hospital

    Bern

    Completed

  • Hospital of Bienne

    Biel/Bienne, Canton of Bern

    Daniel Genné, Prof. MD

    Daniel Genné, Prof., MD

    Recruiting

  • Regional Hospital of Emmental

    Burgdorf

    Robert Escher, PD Dr. MD

    Robert Escher, PD, MD

    Recruiting

  • Hospital of Delémont

    Delémont

    Terminated

  • Cantonal Hospital of Frauenfeld

    Frauenfeld, Thurgau

    Andreas Kistler, PD MD

    Andreas Kistler, PD, MD

    Recruiting

  • Cantonal Hospital of Fribourg

    Fribourg, Canton of Fribourg

    Withdrawn

  • Geneva University Hospital

    Geneva

    Marc Righini, Prof. MD

    Marc Righini, Prof., MD

    Recruiting

  • University Hospital of Lausanne

    Lausanne, Canton of Vaud

    Marie Méan, MD MER

    Marie Méan, MD, MER

    Recruiting

  • Cantonal Hospital of Liestal

    Liestal, Basel

    Jörg Leuppi, Prof. MD PhD

    Jörg Leuppi, Prof., MD, PhD

    Recruiting

  • Cantonal Hospital of Lucerne

    Lucerne, Canton of Lucerne

    Withdrawn

  • Hospital of Neuchâtel

    Neuchâtel

    Jacques Donzé, Prof. MD MSc

    Jacques Donzé, Prof., MD, MSc

    Recruiting

  • Hospital of Nyon

    Nyon, Canton of Vaud

    Withdrawn

  • Cantonal Hospital of Olten

    Olten, Canton of Solothurn

    Withdrawn

  • Cantonal Hospital of St. Gallen

    Sankt Gallen, Canton of St. Gallen

    Claudio S. Rüegg, MD

    Claudio S. Rüegg, MD

    Recruiting

  • Hospital of Sion

    Sion, Valais

    Withdrawn

  • Cantonal Hospital of Winterthur

    Winterthur, Canton of Zurich

    Bettina Portocarrero, MD

    Bettina Portocarrero, MD

    Recruiting

  • Triemli Hospital

    Zurich, Canton of Zurich

    Lars Huber, PD MD

    Lars Huber, PD, MD

    Recruiting

  • University Hospital Zürich

    Zurich, Canton of Zurich

    Withdrawn

Other trials in Switzerland

France8 sites, 8 recruiting

  • Centre Hospitalier Regional Et Universitaire De Brest

    Brest

    Francis Couturaud, Prof. MD

    Francis Couturaud, Prof., MD

    Recruiting

  • CHU Gabriel-Montpied

    Clermont-Ferrand

    Jeannot Schmidt, Prof., MD

    Jeannot Schmidt, Prof., MD

    Recruiting

  • Centre Hospitalier Universitaire De Dijon

    Dijon

    Nicolas Falvo, MD

    Nicolas Falvo, MD

    Recruiting

  • Hôpital Bicêtre - APHP

    Le Kremlin-Bicêtre, Le Kremlin-Bicêtre, 94270

    Mitja Jevnikar, MD, 0145213487, mitja.jevnikar@aphp.fr

    Mitja Jevnikar, MD

    Recruiting

  • Hospital Edouard Herriot

    Lyon

    Judith Catella, MD

    Judith Catella, MD

    Recruiting

  • Hôpitaux universitaires de Marseille Timone AP-HM

    Marseille

    Gabrielle Sarlon, Prof., MD

    Gabrielle Sarlon, Prof., MD

    Recruiting

  • CHU De Rouen

    Rouen

    Sébastien Miranda, MD

    Sébastien Miranda, MD

    Recruiting

  • CHU ST Etienne - Hôpital Nord

    Saint-Priest-en-Jarez

    Laurent Bertoletti, Prof., MD

    Laurent Bertoletti, Prof., MD

    Recruiting

Other trials in France

Netherlands6 sites, 4 recruiting

  • Albert Schweitzer Ziekenhuis Dordrecht

    Dordrecht

    P.E. Westerweel, MD

    P.E. Westerweel, MD

    Recruiting

  • Medisch Spectrum Twente

    Enschede

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

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

    Recruiting

  • Leiden University Medical Center

    Leiden

    F. A. Klok, Prof. MD PhD

    F. A. Klok, Prof., MD, PhD

    Recruiting

  • Erasmus Universitair Medisch Centrum

    Rotterdam

    Withdrawn

  • Haaglanden Medisch Centrum

    The Hague

    Withdrawn

  • Isala Klinieken Zwolle

    Zwolle

    M. F. Boosma, MD

    M. F. Boosma, MD

    Recruiting

Other trials in Netherlands

Belgium2 sites, 2 recruiting

  • Centre hospitalier universitaire de Liege

    Liège

    Raphaelle Lopez Iglesias, MD

    Raphaelle Lopez Iglesias, MD

    Recruiting

  • Cliniques Universitaires Saint-Luc

    Woluwe-Saint-Lambert, Brussels Capital, 1200

    Andrea Penaloza Baeza, Prof., MD

    Andrea Penaloza Baeza, Prof., MD

    Recruiting

Other trials in Belgium

Canada1 site, 1 recruiting

  • The Ottawa Hospital

    Ottawa

    Marc Carrier, Prof. MD MSc

    Marc Carrier, Prof. MD MSc

    Recruiting

Other trials in Canada

About this study

Official title: Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism: a Multicenter Randomized Placebo-controlled Non-inferiority Trial

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.

Being tested
Rivaroxaban, Placebo
Keywords
subsegmental pulmonary embolism
Medical subject headings
Pulmonary Embolism, Embolism, Embolism and Thrombosis, Lung Diseases, Cardiovascular Diseases, Respiratory Tract Diseases, Venous Thromboembolism, Hemorrhage

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RivaroxabanDrug

    Anticoagulation

  • PlaceboDrug

    Study drug without active agent

Study groups in NCT04263038
Study groupRoleWhat they receive
AnticoagulationActive comparatorPatients 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.
Receives: Drug: Rivaroxaban
No anticoagulationPlacebo comparatorPatients 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recurrent venous thromboembolism

    Proportion of recurrent, clinically symptomatic, objectively confirmed venous thromboembolism (defined as recurrent fatal or nonfatal pulmonary embolism or lower limb deep vein thrombosis)

    Measured: Within 90 days of randomization

Secondary outcomes (2)

  1. Clinically significant bleeding

    Proportion of the composite of major and clinically relevant non-major bleeding

    Measured: Within 90 days of randomization

  2. All-cause mortality

    Proportion of deaths (all causes of death will be considered)

    Measured: Within 90 days of randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Feb 2020
  2. Study start15 May 2020
  3. Primary completionMay 2028 (estimated)
  4. Study completionMay 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
276 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04263038
Sponsor's protocol ID
2019-02297
Other IDs
2019
Acronym
SAFE-SSPE
Status last verified
May 2026
First submitted
4 Feb 2020
Last updated
22 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: After publication of the study results, a de-identified patient-level data set relating to the primary publication along with the latest version of the study protocol, the informed consent form, the statistical analysis plan, the code used for the analyses, and the Data Management and Quality Plan describing all data management aspects of the study will be made publicly available for replication of the study results and secondary data analyses in the Bern Open Repository and Information System (BORIS) Research Data, an online non-commercial data repository that meets Swiss National Science Foundation requirements for FAIR Data Principles (www.force11.org/group/fairgroup/fairprinciples)

Publications

  • 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.

    PubMed 33444199

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Rivaroxaban in people with Pulmonary Embolism and Embolism, run by Drahomir Aujesky at 40 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 40 sites in Switzerland, France, Netherlands, Belgium, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Drahomir Aujesky, Prof. MD MSc (+41 31 632 88 84, SAFE-SSPE@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recurrent venous thromboembolism (time frame: Within 90 days of randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04263038, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2026.

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