Safely Ruling Out Deep Vein Thrombosis in Pregnancy With the LEFt Clinical Decision Rule and D-Dimer

Pregnancy Clinical Trial

— LEaD  

Official title:

Safely Ruling Out Deep Vein Thrombosis in Pregnancy With the LEFt Clinical Decision Rule and D-Dimer: the LEaD Study. A Prospective Cohort Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02507180
• Other study ID #: 20150546-01H
• Status: Recruiting
• Start date: September 2015
• Est. completion date: January 2022

Study information

• Verified date: February 2020
• Source: Ottawa Hospital Research Institute
• Contact: Marc A Rodger, MD
• Phone: 514-843-1578
• Email: marc.rodger[@]mcgill.ca
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is prospective cohort study in pregnant women who present with signs and symptoms of possible deep vein thrombosis (DVT). All patients will have the same method of assessment of their DVT symptoms (the LEFt clinical decision rule will be applied and D-dimer test will be done) to determine if a compression ultrasound is required. All patients will be followed for a period of 3 months.

Description:

VTE is a leading cause of maternal death in the developed world. Suspected DVT in pregnancy is a common clinical problem faced by clinicians daily. The only validated method to exclude DVT in pregnancy requires leg vein CUS imaging. This imaging modality is costly and has limited availability (only available in radiology departments and, usually, only during weekday daytime hours) often necessitating referral to the emergency room for initiation of heparin injections until leg vein CUS can be obtained. A simple and seemingly powerful clinical decision rule (LEFt) and a simple blood test (D-dimer) may be promising to exclude DVT in pregnancy without the need for diagnostic imaging. Validating the safety of a simple, non-invasive, widely available approach to suspected DVT in pregnancy would be an important advance in maternal health.

A prospective cohort diagnostic management study in pregnant women with suspected DVT, with three-month follow-up for symptomatic VTE will take place in multiple centres throughout Canada and Europe.

After obtaining informed consent, all patient will have the LEFt clinical decision rule applied by the attending physician and will have D-Dimer testing (D-Dimer results of test performed within 24 hours will be accepted and do not need to be repeated).

Patients with an "unlikely" LEFt score of 0 or 1 point and a negative D-dimer will not undergo diagnostic imaging.

Patients with either a "likely" LEFt score of 2 or 3 points or a positive D-dimer will undergo either a single complete leg vein compression ultrasound (CCUS) (Day 1) or a serial proximal leg vein (CUS) (Day 1 and Day 7).

All patients will be followed for 3 months for symptomatic VTE.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 366
• Est. completion date: January 2022
• Est. primary completion date: September 2021
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

1. Unselected pregnant women (as self-reported by patient and/or previously documented positive beta hCG on urine or serum pregnancy tests) with

2. Suspected acute symptomatic deep vein thrombosis, defined as:

1. New leg swelling or edema with onset in the last month or,

2. New leg pain (buttock, groin, thigh or calf) with onset in the last month.

Exclusion Criteria:

1. Below the age of legal consent in jurisdiction of residence (18 years old for Quebec and 16 years old for rest of Canada)

2. Baseline imaging (imaging done after a minimum of 3 months of treatment for prior proximal DVT) not available if suspected recurrence in the same leg as prior

3. Unable or unwilling to provide informed consent

4. Concomitant symptoms of suspected pulmonary embolism (chest pain or shortness of breath or syncope/pre-syncope or unexplained tachycardia)

5. Therapeutic anticoagulant more than 48 hours.

Related Conditions & MeSH terms

• Deep Vein Thrombosis
• Pregnancy
• Thrombosis
• Venous Thrombosis

Intervention

Other:
• LEFt clinical decision rule
The LEFt rule Predictor Points Left leg symptoms +1 Extremity swelling (= 2 cm difference in calf circumference +1 First trimester symptom onset +1 Clinical probability Unlikely: 0 or 1 point Likely: > 1 point

Locations

Country	Name	City	State
Canada	Foothills Medical Centre	Calgary	Alberta
Canada	Royal Alexandra Hospital	Edmonton	Alberta
Canada	Queen Elizabeth II Health Science Centre	Halifax	Nova Scotia
Canada	Hamilton Health Sciences Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Sunnybrook Medical Hospital	Toronto	Ontario
Canada	Children's and Women's Health Centre of British Columbia	Vancouver	British Columbia
Netherlands	Leiden University Medical Center	Leiden
Switzerland	Hopitaux Universitaires de Geneve	Geneva
United States	Intermountain Healthcare, Inc.	Murray	Utah

Sponsors (3)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Leiden University Medical Center, University Hospital, Geneva

Countries where clinical trial is conducted

United States,  Canada,  Netherlands,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of VTE diagnosed in patients deemed DVT "unlikely"	The primary outcome will be the number of VTE (distal or proximal DVT, sub-segmental or greater pulmonary embolism (PE), death attributable to VTE) documented during the three-month follow-up in those patients left untreated for DVT on the basis of the study's initial diagnostic management (see Figure 2) i.e. not doing CUS on patients with an "unlikely" LEFt score (0 or 1 points) and a negative D-dimer	3 months after presentation
Secondary	Number of VTE diagnosed in all patients	The number of major VTE events (any proximal DVT, segmental or greater PE, death attributable to VTE) documented during the 3-month follow-up in all patients. Some clinicians may not treat distal DVT or sub-segmental PE in pregnancy, instead following these patients with serial US imaging, and hence may prefer to focus on this outcome that excludes distal DVT and sub-segmental PE.	3 months after presentation
Secondary	Proportion of women requiring CUS	The proportion of women requiring CUS using the study's diagnostic strategy (i.e. no imaging in patients with an "unlikely" LEFt score (0 or 1 points) and a negative D-dimer). We anticipate that an important proportion (>40%) of women will be able to avoid the need for CUS imaging based on safely excluding DVT on the basis of an "unlikely" LEFt (0 or 1) and a negative D-dimer. However, if this proportion is very low (<5%) this may argue against the widespread adoption of our proposed diagnostic management strategy even if it proves to be safe.	Baseline
Secondary	Average number of CUS in pregnant women with suspected DVT	The mean number of ultrasounds per patient with suspected DVT. In the study by Chan, validating serial CUS in pregnancy, the mean number of US per patient was 2.8630. We anticipate that we will be able to reduce this by >40% with our diagnostic approach.	7 days from initial presentation