Aspirin, Postpartum Period, Venous Thromboembolism
Conditions
Keywords
deep vein thrombosis, pulmonary embolism, postpartum, pregnancy, thrombophilia, cesarean delivery, pre-eclampsia, postpartum hemorrhage
Brief summary
The pilot PARTUM trial is a randomized, multicenter, placebo-controlled trial. Women who are at modest risk of VTE (as defined by the inclusion criteria) will be identified during pregnancy, labor and delivery and up to 48 hours postpartum. Eligible and consenting participants will be randomly assigned to one of two study arms: aspirin 81 mg daily or placebo daily for 6 weeks.
Detailed description
The purpose of the pilot PARTUM trial is to determine whether it is feasible to conduct a larger randomized controlled trial to determine whether low-dose aspirin is efficacious and safe at preventing postpartum venous thromboembolism (VTE) in women at increased risk of VTE, compared to placebo. Given the large sample size needed to adequately power a large multicenter trial that assesses the efficacy of aspirin 81 mg versus placebo, the investigators first need to determine if it is possible to recruit enough women. If the pilot trial is successful and there are no major changes to the study design, then the secondary clinical outcomes collected in the pilot trial will be used in the analysis of the full multicenter trial.
Interventions
DRUGAspirin 81 mg
Aspirin 81 mg p.o. daily
DRUGPlacebo
Placebo p.o. daily
Sponsors
Canadian Institutes of Health Research (CIHR)
Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
University of Calgary
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Study inclusion criteria includes one (or more) first order criterion or two (or more) second order criteria. A patient is still eligible if they have multiple criteria met, at the discretion of the local investigator. ONE (or more) First Order Criteria: 1. Known inherited thrombophilia diagnosed prior to enrolment: i) Heterozygous factor V Leiden, OR ii) Heterozygous prothrombin gene variant, OR iii) Protein C deficiency, OR iv) Protein S deficiency 2. Immobilization (90% of waking hours spent in bed) for ≥7 days anytime during the antepartum period TWO (or more) Second Order Criteria: 1. Postpartum infection 2. Postpartum hemorrhage (\>1000 mL of blood loss, regardless of delivery mode) 3. Pre-pregnancy BMI ≥30 kg/m2 4. Emergency or unplanned cesarean delivery 5. Smoking ≥5 cigarettes/day before pregnancy 6. Pre-eclampsia 7. Current pregnancy ending in stillbirth (pregnancy loss \>20 weeks gestation) 8. Small-for-gestational-age infant (\<3rd percentile adjusted for gestational age and sex). 9. Previous history of superficial vein thrombosis
Exclusion criteria
1. More than 48 hours since delivery 2. Received more than 2 doses of low-molecular-weight heparin (LMWH) since delivery 3. Need for postpartum LMWH prophylaxis or systemic anticoagulation as judged by the 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 4. Known high-risk inherited thrombophilia i) Antithrombin deficiency; ii) Homozygous factor V Leiden; iii) Homozygous prothrombin gene mutation; iv) Compound heterozygosity factor V Leiden and prothrombin gene mutation; v) More than one inherited thrombophilia 4. Need for postpartum aspirin as judged by the 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. Contraindication to aspirin including: 1. History of known aspirin allergy 2. Documented history of a gastrointestinal ulcer 3. Known platelet count \<50 x 109/L at any time during the current pregnancy or postpartum 4. Active bleeding at any site, excluding normal vaginal bleeding, at the time of randomization 5. Most recent known hemoglobin ≤70 g/L documented during the current pregnancy or postpartum 6. Known severe hypertension (SBP \>200mm/hg and/or DBP \>120mm/hg) during the current pregnancy or postpartum 6. \<18 years of age 7. Unable or refused consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recruitment Rate | 6 months | Mean recruitment rate per center per month |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Withdrawals/Loss to Follow-up | 9 months | Proportion of withdrawals/loss to follow-up among participants |
| Study Drug Compliance | 6 months | Level of compliance with study drug through participant recall and medication diary |
| Consent Rate | 6 months | Proportion of eligible subjects who provide consent |
| VTE Event Rate | 6 months | A more precise estimate of the VTE event rate |
| Bleeding Event Rate | 6 months | A more precise estimate of the major and clinically relevant non-major bleeding event rate |
| Time Required to Obtain Site Institutional Approvals | 24 months | Proportion of sites requiring \>18 months to obtain all required approvals/contracts from time of delivery of all study documents. |
Countries
Canada, France, Ireland, Netherlands
Outcome results
None listed