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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04263038
Recruitment Status : Recruiting
First Posted : February 10, 2020
Last Update Posted : October 20, 2020
Sponsor:
Collaborators:
University of Bern
Schweizerischer Nationalfonds
Leiden University Medical Center
The Ottawa Hospital
Bayer
Information provided by (Responsible Party):
Drahomir Aujesky, University Hospital Inselspital, Berne

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.

Condition or disease Intervention/treatment Phase
Pulmonary Embolism Embolism Embolism and Thrombosis Lung Diseases Cardiovascular Diseases Respiratory Tract Diseases Venous Thromboembolism Anticoagulant-induced Bleeding Bleeding Drug: Rivaroxaban Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 276 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical Surveillance vs. Anticoagulation for Low-risk Patients With Isolated Subsegmental Pulmonary Embolism: a Multicenter Randomized Placebo-controlled Non-inferiority Trial
Actual Study Start Date : May 15, 2020
Estimated Primary Completion Date : February 2024
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Rivaroxaban

Arm Intervention/treatment
Active Comparator: Anticoagulation
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
Anticoagulation

Placebo Comparator: No anticoagulation
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
Study drug without active agent




Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04263038


Contacts
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Contact: Drahomir Aujesky, Prof. MD MSc +41 31 632 88 84 SAFE-SSPE@insel.ch
Contact: Christine Baumgartner, Dr. MD MAS +41 31 632 57 69 SAFE-SSPE@insel.ch

Locations
Show Show 31 study locations
Sponsors and Collaborators
Drahomir Aujesky
University of Bern
Schweizerischer Nationalfonds
Leiden University Medical Center
The Ottawa Hospital
Bayer
Investigators
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Study Director: Drahomir Aujesky, Prof. MD MSc Inselspital, Bern University Hospital, University of Bern
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Responsible Party: Drahomir Aujesky, Prof. Dr., MD, MSc, University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT04263038    
Other Study ID Numbers: 2019-02297
First Posted: February 10, 2020    Key Record Dates
Last Update Posted: October 20, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After publication of the study results, a de-identified patient-level data set relating to the primary publication along with the latest version of the study protocol, the informed consent form, the statistical analysis plan, the code used for the analyses, and the Data Management and Quality Plan describing all data management aspects of the study will be made publicly available for replication of the study results and secondary data analyses in the Bern Open Repository and Information System (BORIS) Research Data, an online non-commercial data repository that meets Swiss National Science Foundation requirements for FAIR Data Principles (www.force11.org/group/fairgroup/fairprinciples)
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Analytic Code
Time Frame: After publication of the study results
Access Criteria: Data will be publicly available for replication of the study results and secondary data analyses in the Bern Open Repository and Information System (BORIS) Research Data
URL: https://www.boris.unibe.ch/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Drahomir Aujesky, University Hospital Inselspital, Berne:
subsegmental pulmonary embolism
Additional relevant MeSH terms:
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Lung Diseases
Pulmonary Embolism
Respiratory Tract Diseases
Cardiovascular Diseases
Thrombosis
Thromboembolism
Embolism
Venous Thromboembolism
Embolism and Thrombosis
Hemorrhage
Pathologic Processes
Vascular Diseases
Rivaroxaban
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants