Clinical trial NCT04263038: Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism
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
Overall status: RECRUITING
Phase: PHASE4
Conditions: Pulmonary Embolism
Embolism
Embolism and Thrombosis
Lung Diseases
Cardiovascular Diseases
Respiratory Tract Diseases
Venous Thromboembolism
Anticoagulant-induced Bleeding
Bleeding
Keywords: subsegmental pulmonary embolism
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University of Bern
name: Schweizerischer Nationalfonds
name: Leiden University Medical Center
name: The Ottawa Hospital
name: Bayer
First posted: 2020-02-10
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Recurrent venous thromboembolism
timeFrame: Within 90 days of randomization
Secondary outcomes:
measure: Clinically significant bleeding
timeFrame: Within 90 days of randomization
measure: All-cause mortality
timeFrame: Within 90 days of randomization
Other outcomes:
measure: Health-related quality of life
timeFrame: Within 90 days of randomization
measure: Functional status
timeFrame: Within 90 days of randomization
measure: Initial length of stay (LOS)
timeFrame: Within 90 days of randomization
measure: Subsequent overall hospitalizations
timeFrame: Within 90 days of randomization
measure: Emergency departments and physician outpatient visits
timeFrame: Within 90 days of randomization
measure: Return to work or usual activities
timeFrame: Within 90 days of randomization
Locations:
city: Liège
country: Belgium
facility: Centre hospitalier universitaire de Liege
city: Sint-Lambrechts-Woluwe
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Ottawa
country: Canada
facility: The Ottawa Hospital
city: Brest
country: France
facility: Centre Hospitalier Regional Et Universitaire De Brest
city: Clermont-Ferrand
country: France
facility: CHU Gabriel-Montpied
city: Dijon
country: France
facility: Centre Hospitalier Universitaire De Dijon
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre - APHP
city: Lyon
country: France
facility: Hospital Edouard Herriot
city: Rouen
country: France
facility: CHU De Rouen
city: Saint-Priest-en-Jarez
country: France
facility: CHU ST Etienne - Hôpital Nord
city: Den Haag
country: Netherlands
facility: Haaglanden Medisch Centrum
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis Dordrecht
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Universitair Medisch Centrum
city: Zwolle
country: Netherlands
facility: Isala Klinieken Zwolle
city: Aarau
country: Switzerland
facility: Cantonal Hospital of Aarau
state: Aargau
city: Liestal
country: Switzerland
facility: Cantonal Hospital of Liestal
state: Basel
city: Bienne
country: Switzerland
facility: Hospital of Bienne
state: Bern
city: Olten
country: Switzerland
facility: Cantonal Hospital of Olten
state: Solothurn
city: Frauenfeld
country: Switzerland
facility: Cantonal Hospital of Frauenfeld
state: Thurgau
city: Sion
country: Switzerland
facility: Hospital of Sion
state: Valais
city: Lausanne
country: Switzerland
facility: University Hospital of Lausanne
state: Vaud
city: Nyon
country: Switzerland
facility: Hospital of Nyon
state: Vaud
city: Winterthur
country: Switzerland
facility: Cantonal Hospital of Winterthur
state: Zurich
city: Altdorf
country: Switzerland
facility: Cantonal Hospital of Uri
city: Baden
country: Switzerland
facility: Cantonal Hospital of Baden
city: Basel
country: Switzerland
facility: University Hospital of Basel
city: Bern
country: Switzerland
facility: University Hospital Inselspital
city: Bern
country: Switzerland
facility: Tiefenau Hospital
city: Burgdorf
country: Switzerland
facility: Regional Hospital of Emmental
city: Delémont
country: Switzerland
facility: Hospital of Delémont
city: Fribourg
country: Switzerland
facility: Cantonal Hospital of Fribourg
city: Geneva
country: Switzerland
facility: Geneva University Hospital
city: Lucerne
country: Switzerland
facility: Cantonal Hospital of Lucerne
city: Neuchâtel
country: Switzerland
facility: Hospital of Neuchâtel
city: St. Gallen
country: Switzerland
facility: Cantonal Hospital of St. Gallen
city: Zürich
country: Switzerland
facility: Triemli Hospital
city: Zürich
country: Switzerland
facility: University Hospital Zürich
Study officials:
affiliation: Inselspital, Bern University Hospital, University of Bern
name: Drahomir Aujesky, Prof. MD MSc
role: STUDY_DIRECTOR
References:
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.