Back to resultsClinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism (SAFE-SSPE)
Primary Purpose
Pulmonary Embolism, Embolism, Embolism and Thrombosis
Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Rivaroxaban
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Embolism focused on measuring subsegmental pulmonary embolism
Eligibility Criteria
Inclusion Criteria:
- Informed Consent as documented by signature
- Age ≥18 years
- Objective diagnosis of symptomatic or asymptomatic isolated SSPE
Exclusion Criteria:
- 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
- Prior enrolment in this trial
Sites / Locations
- The Ottawa HospitalRecruiting
- Centre Hospitalier Regional Et Universitaire De BrestRecruiting
- Haaglanden Medisch CentrumRecruiting
- Albert Schweitzer Ziekenhuis DordrechtRecruiting
- Medisch Spectrum TwenteRecruiting
- Leiden University Medical CenterRecruiting
- Erasmus Universitair Medisch CentrumRecruiting
- Isala Klinieken ZwolleRecruiting
- Cantonal Hospital of AarauRecruiting
- Cantonal Hospital of LiestalRecruiting
- Hospital of BienneRecruiting
- Cantonal Hospital of St. GallenRecruiting
- Cantonal Hospital of OltenRecruiting
- Cantonal Hospital of FrauenfeldRecruiting
- Hospital of SionRecruiting
- University Hospital of LausanneRecruiting
- Hospital of NyonRecruiting
- Cantonal Hospital of WinterthurRecruiting
- Cantonal Hospital of BadenRecruiting
- University Hospital of BaselRecruiting
- University Hospital InselspitalRecruiting
- Tiefenau HospitalRecruiting
- Regional Hospital of EmmentalRecruiting
- Hospital of DelémontRecruiting
- Cantonal Hospital of FribourgRecruiting
- Geneva University HospitalRecruiting
- Cantonal Hospital of LucerneRecruiting
- Hospital of NeuchâtelRecruiting
- Triemli HospitalRecruiting
- University Hospital ZürichRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Anticoagulation
No anticoagulation
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Clinically significant bleeding
Proportion of the composite of major and clinically relevant non-major bleeding
All-cause mortality
Proportion of deaths (all causes of death will be considered)
Full Information
NCT ID
NCT04263038
First Posted
February 4, 2020
Last Updated
September 27, 2023
Sponsor
Drahomir Aujesky
Collaborators
University of Bern, Schweizerischer Nationalfonds, Leiden University Medical Center, The Ottawa Hospital, Bayer
1. Study Identification
Unique Protocol Identification Number
NCT04263038
Brief Title
Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
Acronym
SAFE-SSPE
Official Title
Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism: a Multicenter Randomized Placebo-controlled Non-inferiority Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 15, 2020 (Actual)
Primary Completion Date
February 2024 (Anticipated)
Study Completion Date
April 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Drahomir Aujesky
Collaborators
University of Bern, Schweizerischer Nationalfonds, Leiden University Medical Center, The Ottawa Hospital, Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Embolism, Embolism, Embolism and Thrombosis, Lung Diseases, Cardiovascular Diseases, Respiratory Tract Diseases, Venous Thromboembolism, Anticoagulant-induced Bleeding, Bleeding
Keywords
subsegmental pulmonary embolism
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
276 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Anticoagulation
Arm Type
Active Comparator
Arm Description
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.
Arm Title
No anticoagulation
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Intervention Description
Anticoagulation
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Study drug without active agent
Primary Outcome Measure Information:
Title
Recurrent venous thromboembolism
Description
Proportion of recurrent, clinically symptomatic, objectively confirmed venous thromboembolism (defined as recurrent fatal or nonfatal pulmonary embolism or lower limb deep vein thrombosis)
Time Frame
Within 90 days of randomization
Secondary Outcome Measure Information:
Title
Clinically significant bleeding
Description
Proportion of the composite of major and clinically relevant non-major bleeding
Time Frame
Within 90 days of randomization
Title
All-cause mortality
Description
Proportion of deaths (all causes of death will be considered)
Time Frame
Within 90 days of randomization
Other Pre-specified Outcome Measures:
Title
Health-related quality of life
Description
Pulmonary embolism related quality of life as assessed by the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire
Time Frame
Within 90 days of randomization
Title
Functional status
Description
Functional status as assessed by the post-venous thromboembolism functional status scale
Time Frame
Within 90 days of randomization
Title
Initial length of stay (LOS)
Description
Defined as the time/date of discharge minus time/date of admission at the emergency department
Time Frame
Within 90 days of randomization
Title
Subsequent overall hospitalizations
Description
Number of overall hospitalizations
Time Frame
Within 90 days of randomization
Title
Emergency departments and physician outpatient visits
Description
Number of emergency department and physician outpatient visits
Time Frame
Within 90 days of randomization
Title
Return to work or usual activities
Description
Time (days) to return to work in workers and usual activities (household) in non-workers
Time Frame
Within 90 days of randomization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Informed Consent as documented by signature
Age ≥18 years
Objective diagnosis of symptomatic or asymptomatic isolated SSPE
Exclusion Criteria:
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
Prior enrolment in this trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Drahomir Aujesky, Prof. MD MSc
Phone
+41 31 632 88 84
Email
SAFE-SSPE@insel.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Tobias Tritschler, Dr. MD MSc
Phone
+41 31 63 2 01 46
Email
SAFE-SSPE@insel.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Drahomir Aujesky, Prof. MD MSc
Organizational Affiliation
Inselspital, Bern University Hospital, University of Bern
Official's Role
Study Director
Facility Information:
Facility Name
The Ottawa Hospital
City
Ottawa
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc Carrier, Prof. MD MSc
Facility Name
Centre Hospitalier Regional Et Universitaire De Brest
City
Brest
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francis Couturaud, Prof. MD
Facility Name
Haaglanden Medisch Centrum
City
Den Haag
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
H.M. A. Hofstee, MD
Facility Name
Albert Schweitzer Ziekenhuis Dordrecht
City
Dordrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
P.E. Westerweel, MD
Facility Name
Medisch Spectrum Twente
City
Enschede
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
H.P.A.A. van Veen, MD
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
F. A. Klok, Prof. MD PhD
Facility Name
Erasmus Universitair Medisch Centrum
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M. Kruip, MD
Facility Name
Isala Klinieken Zwolle
City
Zwolle
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M. F. Boosma, MD
Facility Name
Cantonal Hospital of Aarau
City
Aarau
State/Province
Aargau
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe Schütz, Prof. MD MPH
Facility Name
Cantonal Hospital of Liestal
City
Liestal
State/Province
Basel
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jörg Leuppi, Prof. MD PhD
Facility Name
Hospital of Bienne
City
Bienne
State/Province
Bern
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Daniel Genné, Prof. MD
Facility Name
Cantonal Hospital of St. Gallen
City
St. Gallen
State/Province
Saint Gallen
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Claudio S. Rüegg, MD
Facility Name
Cantonal Hospital of Olten
City
Olten
State/Province
Solothurn
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lukas Zimmerli, PD MD EMBA
Facility Name
Cantonal Hospital of Frauenfeld
City
Frauenfeld
State/Province
Thurgau
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andreas Kistler, PD MD
Facility Name
Hospital of Sion
City
Sion
State/Province
Valais
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre-Auguste Petignat, Prof. MD
Facility Name
University Hospital of Lausanne
City
Lausanne
State/Province
Vaud
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Méan, MD MER
Facility Name
Hospital of Nyon
City
Nyon
State/Province
Vaud
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mallory Moret Bochatay, MD
Facility Name
Cantonal Hospital of Winterthur
City
Winterthur
State/Province
Zurich
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reinhard Imoberdorf, MD
Facility Name
Cantonal Hospital of Baden
City
Baden
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maria Wertli, Prof. MD
Facility Name
University Hospital of Basel
City
Basel
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Roland Bingisser, Prof. MD
Facility Name
University Hospital Inselspital
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Drahomir Aujesky, Prof. MD MSc
Facility Name
Tiefenau Hospital
City
Bern
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Manfred Essig, Prof. MD
Facility Name
Regional Hospital of Emmental
City
Burgdorf
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Escher, PD Dr. MD
Facility Name
Hospital of Delémont
City
Delémont
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hervé Duplain, PD Dr. MD
Facility Name
Cantonal Hospital of Fribourg
City
Fribourg
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julien Vaucher, Prof. MD
Facility Name
Geneva University Hospital
City
Geneva
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marc Righini, Prof. MD
Facility Name
Cantonal Hospital of Lucerne
City
Lucerne
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christoph Henzen, Prof. MD
Facility Name
Hospital of Neuchâtel
City
Neuchâtel
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jacques Donzé, Prof. MD MSc
Facility Name
Triemli Hospital
City
Zürich
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lars Huber, PD MD
Facility Name
University Hospital Zürich
City
Zürich
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ksenija Slankamenac, PD, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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)
IPD Sharing Time Frame
After publication of the study results
IPD Sharing 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
IPD Sharing URL
https://www.boris.unibe.ch/
Citations:
PubMed Identifier
33444199
Citation
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.
Results Reference
derived
Learn more about this trial
Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
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