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NCT Number: NCT04263038

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

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.

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Key information

Conditions

Pulmonary Embolism Anticoagulant-induced Bleeding Bleeding Cardiovascular Diseases Embolism Embolism and Thrombosis Hemorrhage Lung Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Respiratory Tract Diseases Thromboembolism Vascular Diseases Venous Thromboembolism

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Cliniques Universitaires Saint-Luc, Woluwe-Saint-Lambert, Brussels Capital, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Rivaroxaban

Drug

Anticoagulation

Placebo

Drug

Study drug without active agent

Primary outcomes

  1. Recurrent venous thromboembolism

    Time frame: 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 outcomes

  1. Clinically significant bleeding

    Time frame: Within 90 days of randomization

    Proportion of the composite of major and clinically relevant non-major bleeding

  2. All-cause mortality

    Time frame: Within 90 days of randomization

    Proportion of deaths (all causes of death will be considered)

Other outcomes

  1. Health-related quality of life

    Time frame: Within 90 days of randomization

    Pulmonary embolism related quality of life as assessed by the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire

  2. Functional status

    Time frame: Within 90 days of randomization

    Functional status as assessed by the post-venous thromboembolism functional status scale

  3. Initial length of stay (LOS)

    Time frame: Within 90 days of randomization

    Defined as the time/date of discharge minus time/date of admission at the emergency department

  4. Subsequent overall hospitalizations

    Time frame: Within 90 days of randomization

    Number of overall hospitalizations

  5. Emergency departments and physician outpatient visits

    Time frame: Within 90 days of randomization

    Number of emergency department and physician outpatient visits

  6. Return to work or usual activities

    Time frame: Within 90 days of randomization

    Time (days) to return to work in workers and usual activities (household) in non-workers

Study contacts

Contact information is provided by the study sponsor or research team.

Drahomir Aujesky, Prof. MD MSc

CONTACT

[email protected]

+41 31 632 88 84

Tobias Tritschler, Dr. MD MSc

CONTACT

[email protected]

+41 31 63 2 01 46

Sponsors and collaborators

Lead sponsor

Drahomir Aujesky

Other

Collaborators

  • Bayer
  • Leiden University Medical Center
  • Schweizerischer Nationalfonds
  • The Ottawa Hospital
  • University of Bern

Registry information

Official study title

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

Acronym: SAFE-SSPE

Important dates

Study start
2020
Primary completion
2028
Study completion
2028
First posted
Feb 10, 2020
Registry last updated
May 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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