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

Cardiovascular Diseases Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04263038
• Other study ID #: 2019-02297
• Status: Recruiting
• Phase: Phase 4
• Start date: May 15, 2020
• Est. completion date: April 2024

Study information

• Verified date: September 2023
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Drahomir Aujesky, Prof. MD MSc
• Phone: +41 31 632 88 84
• Email: SAFE-SSPE[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 276
• Est. completion date: April 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Rivaroxaban
Anticoagulation
• Placebo
Study drug without active agent

Locations

Country	Name	City	State
Canada	The Ottawa Hospital	Ottawa
France	Centre Hospitalier Regional Et Universitaire De Brest	Brest
Netherlands	Haaglanden Medisch Centrum	Den Haag
Netherlands	Albert Schweitzer Ziekenhuis Dordrecht	Dordrecht
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Erasmus Universitair Medisch Centrum	Rotterdam
Netherlands	Isala Klinieken Zwolle	Zwolle
Switzerland	Cantonal Hospital of Aarau	Aarau	Aargau
Switzerland	Cantonal Hospital of Baden	Baden
Switzerland	University Hospital of Basel	Basel
Switzerland	Tiefenau Hospital	Bern
Switzerland	University Hospital Inselspital	Bern
Switzerland	Hospital of Bienne	Bienne	Bern
Switzerland	Regional Hospital of Emmental	Burgdorf
Switzerland	Hospital of Delémont	Delémont
Switzerland	Cantonal Hospital of Frauenfeld	Frauenfeld	Thurgau
Switzerland	Cantonal Hospital of Fribourg	Fribourg
Switzerland	Geneva University Hospital	Geneva
Switzerland	University Hospital of Lausanne	Lausanne	Vaud
Switzerland	Cantonal Hospital of Liestal	Liestal	Basel
Switzerland	Cantonal Hospital of Lucerne	Lucerne
Switzerland	Hospital of Neuchâtel	Neuchâtel
Switzerland	Hospital of Nyon	Nyon	Vaud
Switzerland	Cantonal Hospital of Olten	Olten	Solothurn
Switzerland	Hospital of Sion	Sion	Valais
Switzerland	Cantonal Hospital of St. Gallen	St. Gallen	Saint Gallen
Switzerland	Cantonal Hospital of Winterthur	Winterthur	Zurich
Switzerland	Triemli Hospital	Zürich
Switzerland	University Hospital Zürich	Zürich

Sponsors (6)

Lead Sponsor	Collaborator
Drahomir Aujesky	Bayer, Leiden University Medical Center, Schweizerischer Nationalfonds, The Ottawa Hospital, University of Bern

Countries where clinical trial is conducted

Canada,  France,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Health-related quality of life	Pulmonary embolism related quality of life as assessed by the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire	Within 90 days of randomization
Other	Functional status	Functional status as assessed by the post-venous thromboembolism functional status scale	Within 90 days of randomization
Other	Initial length of stay (LOS)	Defined as the time/date of discharge minus time/date of admission at the emergency department	Within 90 days of randomization
Other	Subsequent overall hospitalizations	Number of overall hospitalizations	Within 90 days of randomization
Other	Emergency departments and physician outpatient visits	Number of emergency department and physician outpatient visits	Within 90 days of randomization
Other	Return to work or usual activities	Time (days) to return to work in workers and usual activities (household) in non-workers	Within 90 days of randomization
Primary	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	Clinically significant bleeding	Proportion of the composite of major and clinically relevant non-major bleeding	Within 90 days of randomization
Secondary	All-cause mortality	Proportion of deaths (all causes of death will be considered)	Within 90 days of randomization