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

• Sponsor: Drahomir Aujesky (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04263038
• Collaborator: University of Bern (Other), Schweizerischer Nationalfonds (Other), Leiden University Medical Center (Other), The Ottawa Hospital (Other), Bayer (Industry)
• Enrollment: 276
• Locations: 30
• Arms: 2
• Anticipated Duration (Months): 46.6
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• Anticipated 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
• Anticipated Primary Completion Date: Feb 1, 2024
• Anticipated Study Completion Date: Apr 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Clinically significant bleeding [Within 90 days of randomization]

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

2. All-cause mortality [Within 90 days of randomization]

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

Other Outcome Measures

1. Health-related quality of life [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 [Within 90 days of randomization]

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

3. Initial length of stay (LOS) [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 [Within 90 days of randomization]

   Number of overall hospitalizations

5. Emergency departments and physician outpatient visits [Within 90 days of randomization]

   Number of emergency department and physician outpatient visits

6. Return to work or usual activities [Within 90 days of randomization]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Ottawa Hospital	Ottawa		Canada
2	Haaglanden Medisch Centrum	Den Haag		Netherlands
3	Albert Schweitzer Ziekenhuis Dordrecht	Dordrecht		Netherlands
4	Medisch Spectrum Twente	Enschede		Netherlands
5	Leiden University Medical Center	Leiden		Netherlands
6	Erasmus Universitair Medisch Centrum	Rotterdam		Netherlands
7	Isala Klinieken Zwolle	Zwolle		Netherlands
8	Cantonal Hospital of Aarau	Aarau	Aargau	Switzerland
9	Cantonal Hospital of Liestal	Liestal	Basel	Switzerland
10	Hospital of Bienne	Bienne	Bern	Switzerland
11	Cantonal Hospital of St. Gallen	St. Gallen	Saint Gallen	Switzerland
12	Cantonal Hospital of Olten	Olten	Solothurn	Switzerland
13	Cantonal Hospital of Frauenfeld	Frauenfeld	Thurgau	Switzerland
14	Cantonal Hospital of Uri	Altdorf	Uri	Switzerland
15	Hospital of Sion	Sion	Valais	Switzerland
16	University Hospital of Lausanne	Lausanne	Vaud	Switzerland
17	Hospital of Nyon	Nyon	Vaud	Switzerland
18	Cantonal Hospital of Winterthur	Winterthur	Zurich	Switzerland
19	Cantonal Hospital of Baden	Baden		Switzerland
20	University Hospital of Basel	Basel		Switzerland
21	University Hospital Inselspital	Bern		Switzerland	3010
22	Tiefenau Hospital	Bern		Switzerland
23	Regional Hospital of Emmental	Burgdorf		Switzerland
24	Hospital of Delémont	Delémont		Switzerland
25	Cantonal Hospital of Fribourg	Fribourg		Switzerland
26	Geneva University Hospital	Geneva		Switzerland
27	Cantonal Hospital of Lucerne	Lucerne		Switzerland
28	Hospital of Neuchâtel	Neuchâtel		Switzerland
29	Triemli Hospital	Zürich		Switzerland
30	University Hospital Zürich	Zürich		Switzerland

Sponsors and Collaborators

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

Investigators

• Study Director: Drahomir Aujesky, Prof. MD MSc, Inselspital, Bern University Hospital, University of Bern

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Drahomir Aujesky, Prof. Dr., MD, MSc, University Hospital Inselspital, Berne
• ClinicalTrials.gov Identifier: NCT04263038
• Other Study ID Numbers: 2019-02297
• First Posted: Feb 10, 2020
• Last Update Posted: Jun 10, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Drahomir Aujesky, Prof. Dr., MD, MSc, University Hospital Inselspital, Berne: subsegmental pulmonary embolism
• Additional relevant MeSH terms: Lung Diseases; Pulmonary Embolism; Respiratory Tract Diseases; Cardiovascular Diseases; Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Embolism and Thrombosis; Hemorrhage; Rivaroxaban

Study Results

No Results Posted as of Jun 10, 2022