Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
SAFE-SSPE
1 other identifier
interventional
276
5 countries
39
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started May 2020
Longer than P75 for phase_4
39 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 4, 2020
CompletedFirst Posted
Study publicly available on registry
February 10, 2020
CompletedStudy Start
First participant enrolled
May 15, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2026
CompletedMay 30, 2025
May 1, 2025
6 years
February 4, 2020
May 23, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (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)
Within 90 days of randomization
Secondary Outcomes (2)
Clinically significant bleeding
Within 90 days of randomization
All-cause mortality
Within 90 days of randomization
Other Outcomes (6)
Health-related quality of life
Within 90 days of randomization
Functional status
Within 90 days of randomization
Initial length of stay (LOS)
Within 90 days of randomization
- +3 more other outcomes
Study Arms (2)
Anticoagulation
ACTIVE 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.
No anticoagulation
PLACEBO 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.
Interventions
Eligibility Criteria
You may qualify if:
- Informed Consent as documented by signature
- Age ≥18 years
- Objective diagnosis of symptomatic or asymptomatic isolated SSPE
You may not qualify if:
- 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)
- 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
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Drahomir Aujeskylead
- University of Berncollaborator
- Schweizerischer Nationalfondscollaborator
- Leiden University Medical Centercollaborator
- The Ottawa Hospitalcollaborator
- Bayercollaborator
Study Sites (39)
Centre hospitalier universitaire de Liege
Liège, Belgium
Cliniques Universitaires Saint-Luc
Woluwe-Saint-Lambert, Belgium
The Ottawa Hospital
Ottawa, Canada
Hôpital Bicêtre - APHP
Le Kremlin-Bicêtre, Le Kremlin-Bicêtre, 94270, France
Centre Hospitalier Regional Et Universitaire De Brest
Brest, France
CHU Gabriel-Montpied
Clermont-Ferrand, France
Centre Hospitalier Universitaire De Dijon
Dijon, France
Hospital Edouard Herriot
Lyon, France
CHU De Rouen
Rouen, France
CHU ST Etienne - Hôpital Nord
Saint-Priest-en-Jarez, France
Albert Schweitzer Ziekenhuis Dordrecht
Dordrecht, Netherlands
Medisch Spectrum Twente
Enschede, Netherlands
Leiden University Medical Center
Leiden, Netherlands
Erasmus Universitair Medisch Centrum
Rotterdam, Netherlands
Haaglanden Medisch Centrum
The Hague, Netherlands
Isala Klinieken Zwolle
Zwolle, Netherlands
Cantonal Hospital of Liestal
Liestal, Basel, Switzerland
Cantonal Hospital of Aarau
Aarau, Canton of Aargau, Switzerland
University Hospital Inselspital
Bern, Canton of Bern, 3010, Switzerland
Hospital of Bienne
Biel/Bienne, Canton of Bern, Switzerland
Cantonal Hospital of Fribourg
Fribourg, Canton of Fribourg, Switzerland
Cantonal Hospital of Lucerne
Lucerne, Canton of Lucerne, Switzerland
Cantonal Hospital of Olten
Olten, Canton of Solothurn, Switzerland
Cantonal Hospital of St. Gallen
Sankt Gallen, Canton of St. Gallen, Switzerland
University Hospital of Lausanne
Lausanne, Canton of Vaud, Switzerland
Hospital of Nyon
Nyon, Canton of Vaud, Switzerland
Cantonal Hospital of Winterthur
Winterthur, Canton of Zurich, Switzerland
Triemli Hospital
Zurich, Canton of Zurich, Switzerland
University Hospital Zürich
Zurich, Canton of Zurich, Switzerland
Cantonal Hospital of Frauenfeld
Frauenfeld, Thurgau, Switzerland
Hospital of Sion
Sion, Valais, Switzerland
Cantonal Hospital of Uri
Altdorf, Switzerland
Cantonal Hospital of Baden
Baden, Switzerland
University Hospital of Basel
Basel, Switzerland
Tiefenau Hospital
Bern, Switzerland
Regional Hospital of Emmental
Burgdorf, Switzerland
Hospital of Delémont
Delémont, Switzerland
Geneva University Hospital
Geneva, Switzerland
Hospital of Neuchâtel
Neuchâtel, Switzerland
Related Publications (1)
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.
PMID: 33444199DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Drahomir Aujesky, Prof. MD MSc
Inselspital, Bern University Hospital, University of Bern
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Prof. Dr., MD, MSc
Study Record Dates
First Submitted
February 4, 2020
First Posted
February 10, 2020
Study Start
May 15, 2020
Primary Completion
May 1, 2026
Study Completion
May 1, 2026
Last Updated
May 30, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
- Time Frame
- After publication of the study results
- Access Criteria
- Data will be publicly available for replication of the study results and secondary data analyses in the Bern Open Repository and Information System (BORIS) Research Data
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)