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

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

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.

Study Overview

• Status: Unknown
• Conditions: Pregnancy; Deep Vein Thrombosis
• Intervention / Treatment: Other: LEFt clinical decision rule

Detailed 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.

• Study Type: Observational
• Enrollment (Anticipated): 366

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • Foothills Medical Centre
      • Contact: Jessica Lee, BA
      • Contact: Alissa Kazakoff, BSc
      • Principal Investigator: Paul Gibson, MD
    • Edmonton, Alberta, Canada
      • Recruiting
      • Royal Alexandra Hospital
      • Contact: Shauna Littlefair, RN
      • Principal Investigator: Rshmi Khurana, MD
  • British Columbia
    • Vancouver, British Columbia, Canada
      • Recruiting
      • Children's and Women's Health Centre of British Columbia
      • Contact: Frannie MacKenzie
      • Principal Investigator: Wee-Shian Chan, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Recruiting
      • Queen Elizabeth II Health Science Centre
      • Contact: Blaine Gallant, RN
  • Ontario
    • Hamilton, Ontario, Canada
      • Recruiting
      • Hamilton Health Sciences Centre
      • Contact: Carolyn Webb, RN
      • Principal Investigator: Shannon Bates, MD
    • London, Ontario, Canada
      • Withdrawn
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Veronica Whitham, BSc
      • Principal Investigator: Marc Rodger, MD
    • Toronto, Ontario, Canada
      • Withdrawn
      • Sunnybrook Medical Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • Recruiting
      • Jewish General Hospital
      • Contact: Carla Strulovitch, RN
      • Principal Investigator: Susam Kahn, MD
• Netherlands
  • Leiden, Netherlands
    • Recruiting
    • Leiden University Medical Center
    • Contact: Erik Klok, MD
    • Principal Investigator: Erik Klok, MD
• Switzerland
  • Geneva, Switzerland
    • Recruiting
    • Hôpitaux Universitaires de Genève
    • Contact: Louise Riberdy, MD
• United States
  • Utah
    • Murray, Utah, United States
      • Not yet recruiting
      • Intermountain Healthcare, Inc.
      • Contact: Scott Stevens, MD
      • Principal Investigator: Scott Stevens, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Unselected pregnant women presenting with suspected deep vein thrombosis

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pregnant women with suspected DVT; Pregnant women presenting with suspected DVT will have the LEFt clinical decision rule applied by the attending physician and will have a clinical D-dimer test done.	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: University Hospital, Geneva; Leiden University Medical Center
• Investigators: Principal Investigator: Marc Rodger, MD, Ottawa Hospital Research Institute; Principal Investigator: Marc Righini, MD, Hôpitaux Universitaires de Genève

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2015
• Primary Completion (ANTICIPATED): September 1, 2021
• Study Completion (ANTICIPATED): January 1, 2022

Study Registration Dates

• First Submitted: July 22, 2015
• First Submitted That Met QC Criteria: July 22, 2015
• First Posted (ESTIMATE): July 23, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 27, 2020
• Last Update Submitted That Met QC Criteria: February 25, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Ultrasound; D-Dimer; Clinical Decision Rule; Suspected Deep Vein Thrombosis; LEFt
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis
• Other Study ID Numbers: 20150546-01H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No