Clinical trial NCT06494878: The PARTUM Trial: Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity
Official title: The PARTUM (Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity) Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Venous Thromboembolism
Postpartum Period
Aspirin
Low Molecular Weight Heparin
Keywords: deep vein thrombosis
pulmonary embolism
postpartum
pregnancy
thrombophilia
cesarean delivery
preeclampsia
small-for-gestational age infant
postpartum hemorrhage
postpartum infection
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2024-07-10
Enrollment: 8805
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Symptomatic VTE
timeFrame: 6 weeks
Secondary outcomes:
measure: Late symptomatic VTE
timeFrame: 90 days
measure: Superficial vein thrombosis
timeFrame: At 6 weeks and at 90 days
measure: Distal deep vein thrombosis
timeFrame: At 6 weeks and at 90 days
measure: Single subsegmental pulmonary embolism (SSPE)
timeFrame: At 6 weeks and at 90 days
measure: Major bleeding
timeFrame: At 6 weeks and at 90 days
measure: Clinically relevant non-major bleeding
timeFrame: At 6 weeks and at 90 days
measure: Wound hematoma requiring intervention
timeFrame: At 6 weeks and at 90 days
measure: Symptomatic arterial thromboembolism
timeFrame: At 6 weeks and at 90 days
measure: Postpartum preeclampsia
timeFrame: At 6 weeks and at 90 days
measure: Heparin-induced thrombocytopenia
timeFrame: At 6 weeks and at 90 days
measure: All-cause mortality
timeFrame: At 6 weeks and at 90 days
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: University of Calgary
name: Leslie Skeith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: Marc Rodger, MD
role: PRINCIPAL_INVESTIGATOR
References: