Pilot PARTUM Trial: Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Pilot Study Assessing the Feasibility of a Randomized Controlled Trial Evaluating Aspirin in Postpartum Women at Risk of Developing Venous Thromboembolism

Conditions
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Aspirin, Venous Thromboembolism, Postpartum Period

Intervention / Treatment
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* Drug: Aspirin 81 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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 Immobilization (90% of waking hours spent in bed) for ≥7 days anytime during the antepartum period TWO (or more) Second Order Criteria: Postpartum infection Postpartum hemorrhage (>1000 mL of blood loss, regardless of delivery mode) Pre-pregnancy BMI ≥30 kg/m2 Emergency or unplanned cesarean delivery Smoking ≥5 cigarettes/day before pregnancy Pre-eclampsia Current pregnancy ending in stillbirth (pregnancy loss >20 weeks gestation) Small-for-gestational-age infant (<3rd percentile adjusted for gestational age and sex). Previous history of superficial vein thrombosis Exclusion Criteria: More than 48 hours since delivery Received more than 2 doses of low-molecular-weight heparin (LMWH) since delivery Need for postpartum LMWH prophylaxis or systemic anticoagulation as judged by the local investigator. May include but is not limited to: Documented history of provoked or unprovoked VTE Mechanical heart valve(s) Known antiphospholipid syndrome 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 Need for postpartum aspirin as judged by the local investigator. May include but is not limited to: Documented history of myocardial infarction Documented history of ischemic stroke or transient ischemic attack (TIA) Contraindication to aspirin including: History of known aspirin allergy Documented history of a gastrointestinal ulcer Known platelet count <50 x 109/L at any time during the current pregnancy or postpartum Active bleeding at any site, excluding normal vaginal bleeding, at the time of randomization Most recent known hemoglobin ≤70 g/L documented during the current pregnancy or postpartum Known severe hypertension (SBP >200mm/hg and/or DBP >120mm/hg) during the current pregnancy or postpartum <18 years of age Unable or refused consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Aspirin<br>Aspirin 81 mg daily for six weeks post-randomization (postpartum) | Drug: Aspirin 81 mg<br>* Aspirin 81 mg p.o. daily<br>* Other names: ASA;|
| Placebo Comparator: Placebo<br>Placebo daily for six weeks post-randomization (postpartum) | Drug: Placebo<br>* Placebo p.o. daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment Rate | Mean recruitment rate per center per month | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consent Rate | Proportion of eligible subjects who provide consent | 6 months | 
| Withdrawals/Loss to Follow-up | Proportion of withdrawals/loss to follow-up among participants | 9 months | 
| Study Drug Compliance | Level of compliance with study drug through participant recall and medication diary | 6 months | 
| Time Required to Obtain Site Institutional Approvals | Proportion of sites requiring >18 months to obtain all required approvals/contracts from time of delivery of all study documents. | 24 months | 
| VTE Event Rate | A more precise estimate of the VTE event rate | 6 months | 
| Bleeding Event Rate | A more precise estimate of the major and clinically relevant non-major bleeding event rate | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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deep vein thrombosis, pulmonary embolism, postpartum, pregnancy, thrombophilia, cesarean delivery, pre-eclampsia, postpartum hemorrhage