Need for Antepartum Thromboprophylaxis in Pregnant Women With One Prior Episode of Venous Thromboembolism (VTE) (ROCITP2)

Prospective Study Assessing the Need for Antepartum Thromboprophylaxis in Pregnant Women With One Prior Episode of Venous Thromboembolism

Pregnant women with a prior history of venous thromboembolism (VTE) are at increased risk of recurrent VTE. Current guidelines assessing the role of prophylaxis in pregnant women with prior VTE are based primarily on expert opinion and the optimal clinical management strategy remains unclear.

This multicentre, prospective cohort study aims to test the following hypotheses:

1. Antepartum prophylaxis with fixed-dose low molecular-weight heparin (LMWH) is safe, convenient and associated with an acceptably low risk of recurrent VTE in women with a single prior episode of VTE that was either unprovoked or associated with a minor transient risk factor. (Moderate risk cohort)
2. Withholding antepartum prophylaxis is safe (recurrence risk <1%) in pregnant women with a single prior episode of VTE provoked by a major transient risk factor. (Low risk cohort)

All study patients will receive 6 weeks of postpartum prophylaxis.

Study Overview

• Status: Unknown
• Conditions: Deep Vein Thrombosis; Venous Thromboembolism; Pulmonary Embolism

• Study Type: Observational
• Enrollment (Anticipated): 203

Contacts and Locations

• Study Contact: Name: Shannon M Bates, MD; Phone Number: 73928 905-521-2100; Email: batesm@mcmaster.ca
• Study Contact Backup: Name: Nancy Lloyd, MSc; Phone Number: 33269 905-522-1155; Email: lloydn@mcmaster.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
      • Contact: James D Douketis, MD; Phone Number: 36178 905-522-1155; Email: jdouket@mcmaster.ca
      • Principal Investigator: James D Douketis, MD
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre
      • Contact: Shannon M Bates, MD; Phone Number: 73928 905-521-2100; Email: batesm@mcmaster.ca
      • Principal Investigator: Shannon M Bates, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Consecutive pregnant women with prior VTE diagnosed with accurate testing.

Description

Inclusion Criteria:

• Confirmed pregnancy (positive serum or urine)
• At least 18 years of age
• History of one prior episode of VTE consisting of DVT (diagnosed by compression ultrasonography [CUS] or venography) and/or PE (diagnosed by ventilation-perfusion [V/Q] lung scintigraphy, computed tomographic pulmonary angiography [CTPA], or traditional pulmonary angiography)

Exclusion Criteria:

• Ongoing need for therapeutic anticoagulation for prevention or treatment of cardioembolic stroke
• Known high-risk thrombophilia (specifically antithrombin deficiency, protein S deficiency, protein C deficiency, homozygosity for the factor V Leiden or prothrombin G20210A mutations, antiphospholipid antibody or compound abnormalities)
• VTE within 3 months of the current pregnancy
• Clinical risk factor for initial episode of VTE, if present, not resolved (excluding pregnancy)
• Known contraindication to anticoagulation (including active, uncontrolled bleeding or major bleed within the previous 4 weeks)
• For patients with prior unprovoked VTE, contraindication to LMWH (including allergy, HIT, impaired renal function, osteoporosis)
• Geographic or social factors precluding follow-up
• Inability or unwillingness to provide informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Prior VTE minor transient risk factor; Pregnant women with a single prior VTE episode that was either unprovoked or associated with a minor transient risk factor - Prophylaxis with fixed-dose LMWH
Prior VTE major transient risk factor; Pregnant women with a single prior VTE episode that was provoked by a major transient risk factor - Surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic venous thromboembolism	Symptomatic objectively confirmed recurrent VTE, including proximal DVT, non-fatal PE, and fatal PE during antepartum period	antepartum period (expected average 7 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic recurrent venous thromboembolism	Symptomatic recurrent VTE antepartum and within first 3 months postpartum	antepartum period (expected average 7 months) and first 3 months postpartum
Symptomatic recurrent pulmonary embolism	Symptomatic objectively confirmed recurrent PE antepartum and within first 3 months postpartum	antepartum period (expected average 7 months) and first 3 months postpartum
Thrombocytopenia or heparin-induced thrombocytopenia (HIT)	Thrombocytopenia or HIT during antepartum period	antepartum period (expected average 7 months)
Symptomatic osteoporosis	Symptomatic osteoporosis antepartum and within first 3 months postpartum	antepartum period (expected average 7 months) and first 3 months postpartum
Other complications	Other complications sufficient to stop treatment (e.g., local and systemic reactions) antepartum and within first 3 months postpartum	antepartum (expected average 7 months) and within first 3 months postpartum
Pregnancy complications and outcomes	Pregnancy complications and outcomes including fetal death, pre-eclampsia, toxemia, intrauterine growth restriction, prematurity during antepartum period	antepartum period (expected average 7 months)
Fetal anomalies	Fetal anomalies	antepartum (expected average 7 months) and during first 3 months postpartum
Major and minor bleeding	Major and minor bleeding	antepartum (expected average 7 months)

Collaborators and Investigators

• Sponsor: Hamilton Health Sciences Corporation
• Collaborators: St. Joseph's Healthcare Hamilton
• Investigators: Principal Investigator: Shannon M Bates, MD, McMaster University Medical Centre

Publications and helpful links

General Publications

• Brill-Edwards P, Ginsberg JS, Gent M, Hirsh J, Burrows R, Kearon C, Geerts W, Kovacs M, Weitz JI, Robinson KS, Whittom R, Couture G; Recurrence of Clot in This Pregnancy Study Group. Safety of withholding heparin in pregnant women with a history of venous thromboembolism. Recurrence of Clot in This Pregnancy Study Group. N Engl J Med. 2000 Nov 16;343(20):1439-44. doi: 10.1056/NEJM200011163432002.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Anticipated): September 1, 2013
• Study Completion (Anticipated): September 1, 2014

Study Registration Dates

• First Submitted: May 19, 2011
• First Submitted That Met QC Criteria: May 20, 2011
• First Posted (Estimate): May 23, 2011

Study Record Updates

• Last Update Posted (Estimate): June 3, 2011
• Last Update Submitted That Met QC Criteria: June 2, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Keywords: thromboembolism; cardiovascular diseases; anticoagulants; venous thrombosis; venous thromboembolism; deep vein thrombosis; pulmonary embolism; thrombosis; enoxaparin; thromboprophylaxis; cardiovascular agents; vascular diseases; tinzaparin; dalteparin; pregnancy complications; embolism and thrombosis; hematologic agents
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism
• Other Study ID Numbers: HHS130511