The PARTUM Trial: Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity

The PARTUM (Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity) Trial

The goal of the PARTUM trial is to determine if taking low-dose aspirin daily for 6 weeks after delivery is similar (non-inferior) to usual care low-molecular-weight heparin injections to prevent venous thromboembolism (VTE: blood clots in the legs or lungs) for postpartum individuals with VTE risk factors.

Study Overview

• Status: Not yet recruiting
• Conditions: Aspirin; Venous Thromboembolism; Postpartum Period; Low Molecular Weight Heparin
• Intervention / Treatment: Drug: Aspirin; Drug: Low-molecular-weight heparin

Detailed Description

The PARTUM trial design is a Prospective Randomized Open Blinded End-point (PROBE) non-inferiority trial. Participants with risk factors for venous thromboembolism (VTE) as defined by the inclusion criteria will be identified during pregnancy, labor and delivery, and up to 48 hours after delivery.

Eligible and consenting participants will be randomly assigned to one of two study arms: Low-dose aspirin (75-100mg according to country availability) daily for 42 days post-randomization, or a usual care site-specific low-molecular-weight-heparin (LMWH) regimen with the dose and duration of LMWH determined by the participant's healthcare provider.

Follow-up will occur at 6 weeks and 90 days post-randomization.

• Study Type: Interventional
• Enrollment (Estimated): 8805
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Leslie Skeith, MD; Phone Number: 403-944-5246; Email: laskeith@ucalgary.ca
• Study Contact Backup: Name: Jill Baxter, BSc; Phone Number: 403-220-7103; Email: jbaxter@ucalgary.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
      • Contact: Leslie Skeith, MD; Phone Number: 403-944-5246; Email: laskeith@ucalgary.ca
      • Contact: Jill Baxter, BSc Kin; Phone Number: 403-220-7103; Email: jbaxter@ucalgary.ca
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
      • Contact: Darine El-Chaar, MD; Phone Number: 613-737-8797; Email: delchaar@toh.ca
    • Toronto, Ontario, Canada, M5G 1Z5
      • Mount Sinai Hospital
      • Contact: A. Kinga Malinowski, MD; Phone Number: 5309 416-586-4800; Email: Ann.Malinowski@sinaihealth.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ONE (or more) First Order Criterion:

  1. Known inherited thrombophilia diagnosed prior to enrolment, regardless of family history of VTE:

     i. Heterozygous factor V Leiden, or ii. Heterozygous prothrombin gene variant, or iii. Protein C deficiency, or iv. Protein S deficiency, and/or

  2. Antepartum immobilization for ≥7 days. Immobilization is defined as bed rest with 90% of waking hours spent in bed at any time during the antepartum period AND/OR

TWO (or more) Second Order Criteria:

1. Pre-pregnancy BMI ≥30 kg/m²
2. Smoking in the current pregnancy or within 3 months prior to pregnancy
3. Previous clinical history of superficial vein thrombosis
4. Preeclampsia
5. Current pregnancy ending in stillbirth (pregnancy loss >20 weeks gestation)
6. Unplanned cesarean delivery (unplanned = not a scheduled cesarean delivery)
7. Small-for-gestational-age infant at time of delivery (<3rd percentile adjusted for gestational age and sex)
8. Peripartum or postpartum infection (symptoms/signs of infection and documented fever and laboratory evidence of infection with positive blood cultures or an elevated white blood cell count based on local laboratory cutoffs)
9. Postpartum hemorrhage (≥1000 mL of blood loss, regardless of delivery mode)

Exclusion Criteria:

1. More than 48 hours since delivery at the time of randomization
2. Received more than 1 dose of LMWH since delivery

3. Need for postpartum LMWH prophylaxis or systemic anticoagulation as judged by their physician and/or local investigator. May include but is not limited to:

   1. Documented history of provoked or unprovoked VTE
   2. Mechanical heart valve(s)
   3. Known antiphospholipid syndrome (APS)
   4. Known high-risk inherited thrombophilia i) Antithrombin deficiency, or ii) Homozygous factor V Leiden, or iii) Homozygous prothrombin gene mutation, or iv) More than 1 thrombophilia: any combination of 2 or more: factor V Leiden, prothrombin gene mutation, protein C deficiency, protein S deficiency

4. Need for postpartum ASA as judged by their physician and/or local investigator. May include but is not limited to:

   1. Documented history of myocardial infarction
   2. Documented history of ischemic stroke or transient ischemic attack (TIA)
5. Active bleeding, excluding normal vaginal bleeding, at the time of randomization
6. Known medical condition as judged by their physician and/or local investigator to be a contraindication to ASA or LMWH including known ASA or LMWH allergy
7. <18 years of age
8. Unable or declined consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aspirin; Low-dose aspirin (75-100 mg) once daily for 6 weeks.	Drug: Aspirin; 75-100 mg taken once daily by mouth.
Active Comparator: Low-molecular-weight heparin; Site-specific low-molecular-weight heparin regimen as prescribed by the treating physician.	Drug: Low-molecular-weight heparin; Low-molecular-weight heparin injections daily as prescribed by the treating physician.; Other Names: Dalteparin, Enoxaparin, Nadroparin, Tinzaparin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Symptomatic VTE	Proximal lower or upper extremity DVT, PE involving segmental or higher arteries or multiple subsegmental arteries, and unusual site [non-limb] venous thromboembolism	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late symptomatic VTE	Proximal lower or upper extremity DVT, PE involving segmental or higher arteries or multiple subsegmental arteries, and unusual site [non-limb] venous thromboembolism	90 days
Superficial vein thrombosis	A non-compressible vein segment on ultrasound that involves the superficial veins in the lower or upper extremity	At 6 weeks and at 90 days
Distal deep vein thrombosis	A non-compressible vein segment on ultrasound involving the deep veins that is distal to the popliteal vein in the lower extremity, or distal to the axillary vein in the upper extremity	At 6 weeks and at 90 days
Single subsegmental pulmonary embolism (SSPE)	Intraluminal filling defect that involves one subsegmental artery only	At 6 weeks and at 90 days
Major bleeding	Based on the ISTH definition	At 6 weeks and at 90 days
Clinically relevant non-major bleeding	Based on the ISTH definition	At 6 weeks and at 90 days
Wound hematoma requiring intervention	Requiring intervention such as hematoma evacuation or wound packing	At 6 weeks and at 90 days
Symptomatic arterial thromboembolism	Ischemic stroke/transient ischemic attack, myocardial infarction, or peripheral arterial embolism	At 6 weeks and at 90 days
Postpartum preeclampsia	New preeclampsia presenting in the postpartum period	At 6 weeks and at 90 days
Heparin-induced thrombocytopenia	According to a priori categories of definite or possible HIT.	At 6 weeks and at 90 days
All-cause mortality		At 6 weeks and at 90 days

Collaborators and Investigators

• Sponsor: University of Calgary
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Marc Rodger, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre; Principal Investigator: Leslie Skeith, MD, University of Calgary

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: June 12, 2024
• First Submitted That Met QC Criteria: July 2, 2024
• First Posted (Actual): July 10, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 26, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: pregnancy; postpartum; postpartum hemorrhage; deep vein thrombosis; pulmonary embolism; preeclampsia; cesarean delivery; thrombophilia; small-for-gestational age infant; postpartum infection
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Anticoagulants; Tinzaparin; Aspirin; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Dalteparin; Nadroparin
• Other Study ID Numbers: REB24-0317

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No