The PARTUM Trial: Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity

Phase 3

Not yet recruiting

• Conditions: Venous Thromboembolism; Low Molecular Weight Heparin; Postpartum Period; Aspirin
• Interventions: Drug: Aspirin; Drug: Low-molecular-weight heparin

• Registration Number: NCT06494878
• Lead Sponsor: University of Calgary

Brief Summary

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.

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 Timeline

• Study First Submitted: 2024-06-12
• Study First Submitted QC: 2024-07-02
• Study First Posted: 2024-07-10
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-03-03
• Study Start: 2025-04
• Primary Completion: 2030-08
• Study Completion: 2030-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 8805

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Aspirin	Aspirin	Low-dose aspirin (75-100 mg) once daily for 6 weeks.
Low-molecular-weight heparin	Low-molecular-weight heparin	Site-specific low-molecular-weight heparin regimen as prescribed by the treating physician.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

Foothills Medical Centre; 🇨🇦 Calgary, Alberta, Canada

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

The Ottawa Hospital - General Campus; 🇨🇦 Ottawa, Ontario, Canada