Clinical Surveillance Vs. Anticoagulation for Low-risk Patients with Isolated Subsegmental Pulmonary Embolism

Phase 4

Recruiting

• Conditions: Pulmonary Embolism; Embolism; Embolism and Thrombosis; Lung Diseases; Respiratory Tract Diseases; Venous Thromboembolism; Bleeding; Cardiovascular Diseases; Anticoagulant-induced Bleeding
• Interventions: Drug: Rivaroxaban; Drug: Placebo

• Registration Number: NCT04263038
• Lead Sponsor: Drahomir Aujesky

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-02-04
• Study First Submitted QC: 2020-02-06
• Study First Posted: 2020-02-10
• Study Start: 2020-05-15
• Status Verified: 2024-11
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-28
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 276

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anticoagulation	Rivaroxaban	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.
No anticoagulation	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Recurrent venous thromboembolism	Within 90 days of randomization	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

Name	Time	Method
Clinically significant bleeding	Within 90 days of randomization	Proportion of the composite of major and clinically relevant non-major bleeding
All-cause mortality	Within 90 days of randomization	Proportion of deaths (all causes of death will be considered)

Trial Locations

Locations (38)

Centre hospitalier universitaire de Liege; 🇧🇪 Liège, Belgium

Cliniques Universitaires Saint-Luc; 🇧🇪 Sint-Lambrechts-Woluwe, Belgium

The Ottawa Hospital; 🇨🇦 Ottawa, Canada

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

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, Netherlands

Cantonal Hospital of Aarau; 🇨🇭 Aarau, Aargau, Switzerland

Cantonal Hospital of Liestal; 🇨🇭 Liestal, Basel, Switzerland

Hospital of Bienne; 🇨🇭 Bienne, Bern, Switzerland

Cantonal Hospital of Olten; 🇨🇭 Olten, Solothurn, Switzerland

Cantonal Hospital of Frauenfeld; 🇨🇭 Frauenfeld, Thurgau, Switzerland

Hospital of Sion; 🇨🇭 Sion, Valais, Switzerland

University Hospital of Lausanne; 🇨🇭 Lausanne, Vaud, Switzerland

Hospital of Nyon; 🇨🇭 Nyon, Vaud, Switzerland

Cantonal Hospital of Winterthur; 🇨🇭 Winterthur, Zurich, Switzerland

Cantonal Hospital of Uri; 🇨🇭 Altdorf, Switzerland

Cantonal Hospital of Baden; 🇨🇭 Baden, Switzerland

University Hospital of Basel; 🇨🇭 Basel, Switzerland

University Hospital Inselspital; 🇨🇭 Bern, Switzerland

Tiefenau Hospital; 🇨🇭 Bern, Switzerland

Cantonal Hospital of St. Gallen; 🇨🇭 St. Gallen, Switzerland

Triemli Hospital; 🇨🇭 Zürich, Switzerland

University Hospital Zürich; 🇨🇭 Zürich, Switzerland

Regional Hospital of Emmental; 🇨🇭 Burgdorf, Switzerland

Hospital of Delémont; 🇨🇭 Delémont, Switzerland

Hospital of Neuchâtel; 🇨🇭 Neuchâtel, Switzerland

Cantonal Hospital of Fribourg; 🇨🇭 Fribourg, Switzerland

Geneva University Hospital; 🇨🇭 Geneva, Switzerland

Cantonal Hospital of Lucerne; 🇨🇭 Lucerne, Switzerland