Post Partum Women, Venous Thromboembolism (VTE)
Conditions
Brief summary
Venous thromboembolism (VTE) is currently the second cause of death in women of reproductive age worldwide. The incidence of VTE during pregnancy is 1.2 to 1.4/1000 women, half of VTE occurring during postpartum and as PE in majority of cases, accounting for 8.8% of maternal deaths. Majority of postpartum VTE occurs in women with one or more moderate risk factors (obesity, caesarean section, postpartum hemorrhage). For these women at intermediate risk, the efficacy and safety of thromboprophylaxis have not been assessed yet during postpartum and international guidelines for pharmacological thromboprophylaxis, based on data extrapolated from other populations, observational studies and small clinical trials are inconsistent across countries. We designed an open-label, randomized, controlled trial, aiming to demonstrate the superiority of a pharmacological thromboprophylaxis strategy with LMWH (LMWH type chosen according to physician / patient's preference) during 6 weeks after delivery (the 6-weeks follow-up visit being matched with usual care) in women at intermediate risk, over no pharmacological thromboprophylaxis.
Interventions
DRUGLow molecular weight heparin
Pharmacological thromboprophylaxis using LMWH at preventive dosage. The choice of subcutaneous LMWH depends on the practice of each center: * Enoxaparine 4000 UI (weight \> 90 kg 6000 UI) * Tinzaparine 3500 UI (weight \> 90 kg 4500 UI) * Dalteparine 5000 UI (weight \> 90 kg 7500 UI) * Nadroparine 2850 UI (weight \> 90 kg 3800 UI).
Sponsors
University Hospital, Brest
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
All critical events (VTE, bleeding and mortality) will be validated by a central, independent clinical events committee (ICEC) which will adjudicate outcomes blinded for treatment allocation (PROBE study).
Intervention model description
This is a multicenter PROBE study (prospective randomized open with blinded evaluation of the endpoints by an independent adjudication committee) with two parallel groups
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women at intermediate risk of VTE during post-partum= with a 3% or more risk of VTE based on a validated prediction model\* or International guidelines (ACCP 2012). * Age over 18 years * Delivery between 6 hours and \< 36 hours * Written informed consent * Definition: Intermediate risk is defined as ≥ 3%, based on risk prediction model developed by Sultan et al taking in account: smoking, varicose veins, obesity, comorbidities, diabetes, pre-eclampsia, post-partum hemorrhage, postpartum infection, emergency or elective section or following ACCP guidelines: one major risk factor or two minor risk factors.
Exclusion criteria
* Previous personal history of VTE * LMWH started during antenatal period * Need for anticoagulation at curative dose * Contraindication to LMWH (previous heparin induced thrombopenia, hemostatic impairment, known severe renal insufficiency) * Women who received more than two doses of LMWH since delivery * Unable or refusal to give informed consent * Aspirin at a daily dose 100 mg or dual antiplatelet therapy * Previous inclusion in Mum-VTE study * Concomitant participation in another therapeutic study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptomatic VTE (DVT or non-fatal or fatal PE) | 6 weeks | Blindly adjudicated objectively confirmed symptomatic VTE (DVT or non-fatal or fatal PE) ) during the first 6-week postpartum period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptomatic VTE (DVT or non-fatal or fatal PE) | 3 months | blindly adjudicated objectively confirmed symptomatic VTE (DVT or non-fatal or fatal PE) during 3-month follow-up period after delivery (entire study period). |
| Major bleeding (as defined by the criteria of the International Society of Thrombosis and Haemostasis) | 6 weeks | Blindly adjudicated major bleeding (as defined by the criteria of the International Society of Thrombosis and Haemostasis) during 6-week study treatment period |
| Clinically relevant non-major bleeding | 6 weeks | Blindly adjudicated clinically relevant non-major bleeding during 6-week study treatment period |
| Net Clinical benefit | 6 weeks | The net clinical benefit of study treatment (composite of symptomatic VTE and major or clinically relevant non major bleeding) during 6-week postpartum period |
| Number of Thrombocytopenia | 6 weeks | Cases of heparin induced thrombocytopenia associated with LMWH during 6-week study treatment period. |
| Mortality | 6 weeks | Blindly adjudicated mortality of all causes during 6-week study treatment period |
| VTE suspicion | 6 weeks | Number of VTE suspicion in interventional and control arm during 6-week study treatment period |
| Treatment compliance | 6 weeks | Treatment compliance during 6-week study treatment period based on Girerd questionnaire |
| Objectively confirmed symptomatic VTE (DVT or non-fatal or fatal PE) | 6 weeks | \- Blindly adjudicated objectively confirmed symptomatic VTE (DVT or non-fatal or fatal PE) during the first 6-week postpartum period (i.e., study treatment period) in clinically relevant prespecified subgroups (caesarean section, obesity, age 35 y, smoker during pregnancy, pre-term birth \< 37, pre-eclampsia, postpartum infection, postpartum hemorrhage, VTE family history). |
Countries
France
Contacts
CONTACTEmmanuelle LE MOIGNE, MD, PhD
CONTACTSarah ROBIN, MD
PRINCIPAL_INVESTIGATOREmmanuelle LE MOIGNE, MD, PhD
CHU de Brest
Outcome results
None listed