This is a randomized-controlled open-label trial comparing two different doses of low-molecular-weight heparin (LMWH) in pregnant patients with a history of previous venous thromboembolism (VTE). Both doses are recommended doses in the 2012 guidelines of the American College of Chest Physicians (ACCP), but it is not known which dose is more efficacious in preventing recurrent venous thromboembolism in pregnancy. Patients enter the study and will be randomized as soon as a home test confirms pregnancy. LMWH will be administered until 6 weeks postpartum. Follow-up will continue until 3 months postpartum. Patients will be recruited by their treating physician, either an obstetrician or internist.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
1,110
Fixed low dose nadroparin: * \< 100 kg: 2850 IU subcutaneously once-daily * 100 kg and above: 3800 IU subcutaneously once-daily
Intermediate weight-adjusted dose nadroparin: * \< 50 kg: 3800 IU subcutaneously once-daily; * 50 to \< 70 kg: 5700 IU subcutaneously once-daily; * 70 to \< 100 kg: 7600 IU subcutaneously once-daily; * 100 kg or above: 9500 IU subcutaneously once-daily.
Fixed low dose enoxaparin: * \< 100 kg: 40 mg subcutaneously once-daily * 100 kg and above: 60 mg subcutaneously once-daily
Intermediate weight-adjusted dose enoxaparin: * \< 50 kg: 60 mg subcutaneously once-daily, or; * 50 kg to \< 70 kg: 80 mg subcutaneously once-daily, or; * 70 kg to \< 100 kg: 100 mg subcutaneously once-daily, or; * 100 kg or above: 120 mg subcutaneously once-daily.
Fixed low dose dalteparin: * \< 100 kg: 5000 IU subcutaneously once-daily * 100 kg and above: 7500 IU subcutaneously once-daily
Intermediate weight-adjusted dose dalteparin: * \< 50 kg: 7500 IU subcutaneously once-daily, or; * 50 kg to \< 70 kg: 10000 IU subcutaneously once-daily, or; * 70 kg to \< 100 kg: 12500 IU subcutaneously once-daily, or; * 100 kg or above: 15000 IU subcutaneously once-daily.
Fixed low dose tinzaparin: * \< 100 kg: 3500 IU subcutaneously once-daily * 100 kg and above: 4500 IU subcutaneously once-daily
Intermediate weight-adjusted dose tinzaparin: * \< 50 kg: 4500 IU subcutaneously once-daily, or; * 50 kg to \< 70 kg: 7000 IU subcutaneously once-daily, or; * 70 kg to \< 100 kg: 10000 IU subcutaneously once-daily, or; * 100 kg or above: 12000 IU subcutaneously once-daily.
Weill Cornell Medicine | NewYork-Presbyterian
New York, New York, United States
KU Leuven
Leuven, Belgium
The Ottawa Hospital
Ottawa, Canada
Aalborg University Hospital
Aalborg, Denmark
Aarhus University Hospital
Aarhus, Denmark
CHU de Besancon
Symptomatic confirmed deep venous thrombosis
All events of symptomatic deep venous thrombosis in subjects will be recorded from the the date of randomization up to 6 weeks postpartum. Definition of symptomatic deep venous thrombosis (DVT): Suspected (recurrent) DVT with one of the following findings: If there were no previous DVT investigations: * Abnormal compression ultrasound (CUS), * An intraluminal filling defect on venography. If there was a previous DVT investigation: * Abnormal CUS where compression had been normal or, if non-compressible during screening, a substantial increase (4 mm or more) in diameter of the thrombus during full compression, * An extension of an intraluminal filling defect, or a new intraluminal filling defect or an extension of non-visualization of veins in the presence of a sudden cut-off on venography.
Time frame: From date of randomization up to 6 weeks postpartum
Symptomatic confirmed pulmonary embolism
All events of symptomatic pulmonary embolism in subjects will be recorded from the the date of randomization up to 6 weeks postpartum. Definition of symptomatic pulmonary embolism (PE): Suspected PE with one of the following findings: * A (new) intraluminal filling defect in subsegmental or more proximal branches on spiral CT scan * A (new) intraluminal filling defect or an extension of an existing defect or a new sudden cut-off of vessels more than 2.5 mm in diameter on the pulmonary angiogram * A (new) perfusion defect of at least 75% of a segment with a local normal ventilation result (high-probability) on ventilation/perfusion lung scan (VPLS)
Time frame: From date of randomization up to 6 weeks postpartum
Symptomatic confirmed deep venous thrombosis
All events of symptomatic deep venous thrombosis in subjects will be recorded from the the date of randomization up to 3 months postpartum. Definition of symptomatic deep venous thrombosis (DVT): Suspected (recurrent) DVT with one of the following findings: If there were no previous DVT investigations: * Abnormal compression ultrasound (CUS), * An intraluminal filling defect on venography. If there was a previous DVT investigation: * Abnormal CUS where compression had been normal or, if non-compressible during screening, a substantial increase (4 mm or more) in diameter of the thrombus during full compression, * An extension of an intraluminal filling defect, or a new intraluminal filling defect or an extension of non-visualization of veins in the presence of a sudden cut-off on venography.
Time frame: From date of randomization up to 3 months postpartum
Symptomatic confirmed pulmonary embolism
All events of symptomatic pulmonary embolism in subjects will be recorded from the the date of randomization up to 3 months postpartum. Definition of symptomatic pulmonary embolism (PE): Suspected PE with one of the following findings: * A (new) intraluminal filling defect in subsegmental or more proximal branches on spiral CT scan * A (new) intraluminal filling defect or an extension of an existing defect or a new sudden cut-off of vessels more than 2.5 mm in diameter on the pulmonary angiogram * A (new) perfusion defect of at least 75% of a segment with a local normal ventilation result (high-probability) on ventilation/perfusion lung scan (VPLS)
Time frame: From date of randomization up to 3 months postpartum
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Besançon, France
CHU de Bordeaux
Bordeaux, France
CHU de Brest
Brest, France
CHU de Caen
Caen, France
CHU de Clermont - Ferrand
Clermont-Ferrand, France
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