Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism (SAFE-SSPE)

Drahomir Aujesky

Status and phase: Enrolling; Phase 4

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

Treatments: Drug: Placebo; Drug: Rivaroxaban

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04263038

2019-02297

Details and patient eligibility

About

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.

Enrollment: 276 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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276 participants in 2 patient groups, including a placebo group

Anticoagulation

Active Comparator group

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.

Treatment:

Drug: Rivaroxaban

No anticoagulation

Placebo Comparator group

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.

Treatment:

Drug: Placebo