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

• ClinicalTrials.gov Identifier: NCT01455818
• Recruitment Status: Completed
• First Posted: October 20, 2011
• Last Update Posted: May 28, 2021
• Sponsor: Ottawa Hospital Research Institute
• Collaborator: University Hospital, Brest
• Information provided by (Responsible Party): Ottawa Hospital Research Institute

Tracking Information

• First Submitted Date: October 18, 2011
• First Posted Date: October 20, 2011
• Last Update Posted Date: May 28, 2021
• Study Start Date: March 2011
• Actual Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2012)

Recurrent VTE [ Time Frame: 90 day follow-up ]

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: December 7, 2012)

• Interobserver agreement for SSPE diagnosis on CTPA (local Vs. central interpretation) [ Time Frame: 90 day follow-up ]
• Death due to PE [ Time Frame: 90 day follow-up ]
  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
• Death probably due to PE [ Time Frame: 90 day follow-up ]
  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
• Major bleeding [ Time Frame: 90 day follow-up ]
  Major bleeding will be defined according to previously published criteria (51):

  1. Fatal bleeding; OR
  2. Symptomatic bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome; OR
  3. 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
• Minor bleeding [ Time Frame: 90 day follow-up ]
  Minor bleeding will be defined as any bleeding not meeting the requirements of a major bleeding event.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Safety of Withholding Anticoagulation in Patients With Subsegmental PE Who Have a Negative Serial Bilateral Lower Extremity Ultrasound
• Official Title: 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

Brief Summary

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.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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.
• Condition: Subsegmental (Single or Multiple) Pulmonary Embolism
• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 27, 2021): 292
• Original Estimated Enrollment (submitted: October 19, 2011): 300
• Actual Study Completion Date: May 2021
• Actual Primary Completion Date: March 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, France, Switzerland

Administrative Information

• NCT Number: NCT01455818
• Other Study ID Numbers: 2009600-01H
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ottawa Hospital Research Institute
• Original Responsible Party: Dr. Marc Carrier, Ottawa Hospital Research Institute, Scientist
• Current Study Sponsor: Ottawa Hospital Research Institute
• Original Study Sponsor: Same as current
• Collaborators: University Hospital, Brest
• Investigators: Not Provided
• PRS Account: Ottawa Hospital Research Institute
• Verification Date: May 2021