Clinical trial NCT04153760: Pilot PARTUM Trial: Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity
Official title: A Pilot Study Assessing the Feasibility of a Randomized Controlled Trial Evaluating Aspirin in Postpartum Women at Risk of Developing Venous Thromboembolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Venous Thromboembolism
Postpartum Period
Aspirin
Keywords: deep vein thrombosis
pulmonary embolism
postpartum
pregnancy
thrombophilia
cesarean delivery
pre-eclampsia
postpartum hemorrhage
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Canadian Venous Thromboembolism Clinical Trials and Outcomes Research (CanVECTOR) Network
First posted: 2019-11-06
Enrollment: 257
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 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.

Eligibility criteria: 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

Primary outcomes:
measure: Recruitment Rate
timeFrame: 6 months
Secondary outcomes:
measure: Consent Rate
timeFrame: 6 months
measure: Withdrawals/Loss to Follow-up
timeFrame: 9 months
measure: Study Drug Compliance
timeFrame: 6 months
measure: Time Required to Obtain Site Institutional Approvals
timeFrame: 24 months
measure: VTE Event Rate
timeFrame: 6 months
measure: Bleeding Event Rate
timeFrame: 6 months
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Foothills Medical Centre
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Women's Hospital & Health Centre
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Saint-Étienne
country: France
facility: Centre Hospitalier Universitaire de Saint-Etienne
state: Loire
city: Dublin
country: Ireland
facility: Rotunda Hospital
city: Amsterdam
country: Netherlands
facility: The Amsterdam Medical Centre
state: North Holland
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:
citation: Middleton P, Shepherd E, Gomersall JC. Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period. Cochrane Database Syst Rev. 2021 Mar 29;3(3):CD001689. doi: 10.1002/14651858.CD001689.pub4.