A Study to Evaluate the Safety of Withholding Anticoagulation in Patients With Subsegmental PE Who Have a Negative Serial Bilateral Lower Extremity Ultrasound (SSPE)

A Multicenter Prospective Cohort Management Study to Evaluate the Safety of Withholding Anticoagulation in Patients With Subsegmental PE Who Have a Negative Serial Bilateral Lower Extremity Ultrasound

Blood clots in lung arteries (pulmonary embolism) are usually detected using a radiological test called computed tomography (CT scan). As technology advances, the CT scans are able to detect smaller and smaller blood clots. Over time, the frequency of blood clots in the pulmonary arteries has increased significantly (CT scan are now detecting very small blood clots that the investigators could not see before). As a result, more and more people are on blood thinners to treat these small blood clots but their true clinical significance is unknown.

The management of blood thinners is costly and also utilizes scarce healthcare resources. These blood thinners need to be monitored with frequent blood work. Furthermore, every year, approximately 3 percent of patients on blood thinners will have a major bleeding event requiring medical attention.

The investigators don't think that treating these small blood clots in the pulmonary arteries detected on CT scan is worth the risk of bleeding from the blood thinners.

The main goal of this study is to find out if it is safe to not treat very small blood clots in the pulmonary arteries.

The investigators plan to follow 300 patients with small blood clots in their lungs for 90 days. These patients will not be treated with blood thinners but will be followed closely with other non-invasive tests to avoid progression or recurrence of blood clots.

Study Overview

• Status: Completed
• Conditions: Subsegmental (Single or Multiple) Pulmonary Embolism

• Study Type: Observational
• Enrollment (Actual): 292

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Capital District Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • London, Ontario, Canada
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Sir Mortimer B. Davis Jewish General Hospital
    • Montreal, Quebec, Canada, H3T 1MS
      • St. Mary's Hospital Centre
• France
  • Brest, France
    • Centre Hospitalier Universitaire de Brest
• Switzerland
  • Geneva, Switzerland
    • Geneva Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients with symptomatic, isolated SSPE* (any number), that are newly diagnosed by computed tomographic pulmonary angiography will be eligible to participate in the study.

Description

Inclusion Criteria:

1. Age greater or equal to 18 years old.

2. Patients with newly diagnosed isolated SSPE* (any number).

   • Isolated SSPE is defined as CTPA demonstrating an intraluminal filling defect in a subsegmental artery with no filling defects visualized at more proximal pulmonary artery levels.

Exclusion Criteria:

1. Proximal lower extremity (popliteal vein or above) or upper extremity (subclavian vein or above) DVT.
2. Need for long term oral anticoagulant therapy for reasons other than VTE.
3. SSPE diagnosed in a hospitalized patient (> 48 hours after hospital admission).
4. Requiring oxygen therapy to maintain an O2 saturation over 92%
5. Previous history of DVT (proximal or distal) of upper or lower extremities, PE, or unusual site thrombosis (e.g. splanchnic or cerebral vein thrombosis).
6. Geographically inaccessible for follow-up
7. Active Malignancy (defined as other than basal-cell or squamous cell carcinoma of the skin; cancer within the past 6 months; any treatment for cancer in the past 6 months; or recurrent or metastatic cancer)
8. Pregnancy

9. Have received more than 48 hours of therapeutic anticoagulation.

   • Prophylactic dose allowed if required for separate indication and acceptable by the investigator.
10. Unable/refuse to sign informed consent
11. Asymptomatic SSPE (e.g. SSPE is an incidental finding on a CT scan conducted for reasons other than suspected PE)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent VTE	Recurrent VTE will be diagnosed according to previously published criteria: 1)Lower extremity US revealing non-compressibility at the trifurcation of the popliteal vein or above; OR 2) Venography demonstrating a constant intraluminal filling defect above the trifurcation of the popliteal vein; OR 3) Pulmonary angiography demonstrating a new constant intraluminal filling defect or a cut off of a vessel; OR 4) Ventilation/perfusion scanning with a high probability of PE; OR 5) CTPA demonstrating new intraluminal filling defect in a subsegmental or greater sized pulmonary artery; OR 6) PE discovered at autopsy.	90 day follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interobserver agreement for SSPE diagnosis on CTPA (local Vs. central interpretation)		90 day follow-up
Death due to PE	Definition of death due to PE Certain: hypotension, hypoxia, cardiac arrest with no other explanation other than PE and autopsy or radiographic confirmation Highly probable: criteria for certain but another disease could have caused the death Probable: other cause suspected based on clinical evidence but 100% certainty not available Unlikely: all other cases	90 day follow-up
Death probably due to PE	Certain: hypotension, hypoxia, cardiac arrest with no other explanation other than PE and autopsy or radiographic confirmation Highly probable: criteria for certain but another disease could have caused the death Probable: other cause suspected based on clinical evidence but 100% certainty not available Unlikely: all other cases	90 day follow-up
Major bleeding	Major bleeding will be defined according to previously published criteria (51): Fatal bleeding; OR; Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome; OR; Bleeding causing a fall in hemoglobin level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells	90 day follow-up
Minor bleeding	Minor bleeding will be defined as any bleeding not meeting the requirements of a major bleeding event.	90 day follow-up

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: University Hospital, Brest

Publications and helpful links

General Publications

• Le Gal G, Kovacs MJ, Bertoletti L, Couturaud F, Dennie C, Hirsch AM, Huisman MV, Klok FA, Kraaijpoel N, Mallick R, Pecarskie A, Pena E, Phillips P, Pichon I, Ramsay T, Righini M, Rodger MA, Roy PM, Sanchez O, Schmidt J, Schulman S, Shivakumar S, Trinh-Duc A, Verdet R, Vinsonneau U, Wells P, Wu C, Yeo E, Carrier M; SSPE Investigators. Risk for Recurrent Venous Thromboembolism in Patients With Subsegmental Pulmonary Embolism Managed Without Anticoagulation : A Multicenter Prospective Cohort Study. Ann Intern Med. 2022 Jan;175(1):29-35. doi: 10.7326/M21-2981. Epub 2021 Nov 23.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): May 1, 2021

Study Registration Dates

• First Submitted: October 18, 2011
• First Submitted That Met QC Criteria: October 19, 2011
• First Posted (Estimate): October 20, 2011

Study Record Updates

• Last Update Posted (Actual): May 28, 2021
• Last Update Submitted That Met QC Criteria: May 27, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Pulmonary Embolism
• Other Study ID Numbers: 2009600-01H