The PARTUM Trial: Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity

Official title

The PARTUM (Postpartum Aspirin to Reduce Thromboembolism Undue Morbidity) Trial

Overview

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.

Interventions

• Drug Aspirin
  75-100 mg taken once daily by mouth.
• Drug Low-molecular-weight heparin
  Low-molecular-weight heparin injections daily as prescribed by the treating physician.

Primary outcome measures

• Symptomatic VTE [Time frame: 6 weeks]

Secondary outcome measures (11)

• Late symptomatic VTE [Time frame: 90 days]
• Superficial vein thrombosis [Time frame: At 6 weeks and at 90 days]
• Distal deep vein thrombosis [Time frame: At 6 weeks and at 90 days]
• Single subsegmental pulmonary embolism (SSPE) [Time frame: At 6 weeks and at 90 days]
• Major bleeding [Time frame: At 6 weeks and at 90 days]
• Clinically relevant non-major bleeding [Time frame: At 6 weeks and at 90 days]
• Wound hematoma requiring intervention [Time frame: At 6 weeks and at 90 days]
• Symptomatic arterial thromboembolism [Time frame: At 6 weeks and at 90 days]
• Postpartum preeclampsia [Time frame: At 6 weeks and at 90 days]
• Heparin-induced thrombocytopenia [Time frame: At 6 weeks and at 90 days]
• All-cause mortality [Time frame: At 6 weeks and at 90 days]

Eligibility criteria

Inclusion criteria

• ONE (or more) First Order Criterion:

• 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

• 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:

• Pre-pregnancy BMI ≥30 kg/m²
• Smoking in the current pregnancy or within 3 months prior to pregnancy
• Previous clinical history of superficial vein thrombosis
• Preeclampsia
• Current pregnancy ending in stillbirth (pregnancy loss >20 weeks gestation)
• Unplanned cesarean delivery (unplanned = not a scheduled cesarean delivery)
• Small-for-gestational-age infant at time of delivery (<3rd percentile adjusted for gestational age and sex)
• 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)
• Postpartum hemorrhage (≥1000 mL of blood loss, regardless of delivery mode)

Exclusion criteria

• More than 48 hours since delivery at the time of randomization
• Received more than 1 dose of LMWH since delivery
• Need for postpartum LMWH prophylaxis or systemic anticoagulation as judged by their physician and/or local investigator. May include but is not limited to:

• Documented history of provoked or unprovoked VTE
• Mechanical heart valve(s)
• Known antiphospholipid syndrome (APS)
• 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
• Need for postpartum ASA as judged by their physician and/or local investigator. May include but is not limited to:

• Documented history of myocardial infarction
• Documented history of ischemic stroke or transient ischemic attack (TIA)
• Active bleeding, excluding normal vaginal bleeding, at the time of randomization
• 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
• <18 years of age
• Unable or declined consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

France · 4 centers

• CHU de Nancy — Nancy
• APHP - Hôpital Port Royal — Paris
• CHU de Saint-Etienne — Saint-Etienne
• CHU de Toulouse — Toulouse

Canada · 2 centers

• Foothills Medical Centre — Calgary
• The Ottawa Hospital - General Campus — Ottawa

Ireland · 2 centers

• Rotunda Hospital, RCSI Department of Obstetrics and Gynaecology — Dublin
• UCD Centre for Human Reproduction, The Coombe Hospital — Dublin

Belgium · 1 center

• Association Hospitalière De Bruxelles Et De Schaerbeek - Centre Hospitalier Universitaire — Brussels

Denmark · 1 center

• Hvidovre Hospital — Hvidovre

Netherlands · 1 center

• Amsterdam UMC — Amsterdam

Poland · 1 center

• Medical University of Warsaw — Warsaw

Identifiers

NCT: NCT06494878 · REB24-0317

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗