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

Study Overview
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Brief Summary
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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.

Official Title
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Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism: a Multicenter Randomized Placebo-controlled Non-inferiority Trial

Conditions
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Respiratory Tract Diseases, Pulmonary Embolism, Embolism, Embolism and Thrombosis, Lung Diseases, Cardiovascular Diseases, Venous Thromboembolism, Anticoagulant-induced Bleeding, Bleeding

Intervention / Treatment
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* Drug: Rivaroxaban
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Anticoagulation<br>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. | Drug: Rivaroxaban<br>* Anticoagulation<br>|
| Placebo Comparator: No anticoagulation<br>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. | Drug: Placebo<br>* Study drug without active agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subsegmental pulmonary embolism