Comparison of Low and Intermediate Dose Low-molecular-weight Heparin to Prevent Recurrent Venous Thromboembolism in Pregnancy
- Conditions
- Pulmonary EmbolismDeep Venous Thrombosis
- Interventions
- Registration Number
- NCT01828697
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 1110
- Age: 18 years or older, and;
- Pregnancy confirmed by urinary pregnancy test, and;
- Gestational age < 14 weeks, and;
- Previous objectively confirmed VTE, either unprovoked, in the presence of use of oral contraceptives or estrogen/progestagen use, or related to pregnancy or the postpartum period, or minor risk factors (e.g. long distance travel, minor trauma).
- Previous VTE related to a major provoking risk factor (e.g. surgery, major trauma or plaster cast immobilisation in the 3 months prior to VTE) as the sole risk factor, or;
- Indication for treatment with therapeutic dose anticoagulant therapy (e.g. treatment of acute VTE; permanent use of therapeutic anticoagulants outside of pregnancy), or;
- Inability to provide informed consent, or;
- Any contraindication listed in the local labelling of LMWH.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low dose LMWH Fixed low dose tinzaparin Fixed low dose low-molecular-weight heparin: * Fixed low dose nadroparin, or; * Fixed low dose enoxaparin, or; * Fixed low dose dalteparin, or; * Fixed low dose tinzaparin. Low dose LMWH Low dose nadroparin Fixed low dose low-molecular-weight heparin: * Fixed low dose nadroparin, or; * Fixed low dose enoxaparin, or; * Fixed low dose dalteparin, or; * Fixed low dose tinzaparin. Low dose LMWH Low dose enoxaparin Fixed low dose low-molecular-weight heparin: * Fixed low dose nadroparin, or; * Fixed low dose enoxaparin, or; * Fixed low dose dalteparin, or; * Fixed low dose tinzaparin. Low dose LMWH Low dose dalteparin Fixed low dose low-molecular-weight heparin: * Fixed low dose nadroparin, or; * Fixed low dose enoxaparin, or; * Fixed low dose dalteparin, or; * Fixed low dose tinzaparin. Intermediate dose LMWH Intermediate dose nadroparin Intermediate dose low-molecular-weight heparin. Dosing is weight-adjusted according to the protocol. * Intermediate dose nadroparin, or; * Intermediate dose enoxaparin, or; * Intermediate dose dalteparin, or; * Intermediate dose tinzaparin. Intermediate dose LMWH Intermediate dose enoxaparin Intermediate dose low-molecular-weight heparin. Dosing is weight-adjusted according to the protocol. * Intermediate dose nadroparin, or; * Intermediate dose enoxaparin, or; * Intermediate dose dalteparin, or; * Intermediate dose tinzaparin. Intermediate dose LMWH Intermediate dose dalteparin Intermediate dose low-molecular-weight heparin. Dosing is weight-adjusted according to the protocol. * Intermediate dose nadroparin, or; * Intermediate dose enoxaparin, or; * Intermediate dose dalteparin, or; * Intermediate dose tinzaparin. Intermediate dose LMWH Intermediate dose tinzaparin Intermediate dose low-molecular-weight heparin. Dosing is weight-adjusted according to the protocol. * Intermediate dose nadroparin, or; * Intermediate dose enoxaparin, or; * Intermediate dose dalteparin, or; * Intermediate dose tinzaparin.
- Primary Outcome Measures
Name Time Method Symptomatic confirmed deep venous thrombosis From date of randomization up to 6 weeks postpartum 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.Symptomatic confirmed pulmonary embolism From date of randomization up to 6 weeks postpartum 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)
- Secondary Outcome Measures
Name Time Method Symptomatic confirmed deep venous thrombosis From date of randomization up to 3 months postpartum 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.Symptomatic confirmed pulmonary embolism From date of randomization up to 3 months postpartum 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)
Trial Locations
- Locations (72)
CHU de Besancon
🇫🇷Besançon, France
CHU de Brest
🇫🇷Brest, France
Marseille St Joseph
🇫🇷Marseille, France
CHU de Bordeaux
🇫🇷Bordeaux, France
KU Leuven
🇧🇪Leuven, Belgium
CHU de Nancy
🇫🇷Nancy, France
CHU de Grenoble
🇫🇷Grenoble, France
CHU de Limoges
🇫🇷Limoges, France
Coombe Women's Hospital
🇮🇪Dublin, Ireland
CHU de Caen
🇫🇷Caen, France
Polyclinique de Sète
🇫🇷Sète, France
University Hospital Limerick
🇮🇪Limerick, Ireland
Spaarne Gasthuis
🇳🇱Haarlem, Netherlands
MUMC
🇳🇱Maastricht, Netherlands
St. Radboud UMC
🇳🇱Nijmegen, Netherlands
Erasmus MC
🇳🇱Rotterdam, Netherlands
Aarhus University Hospital
🇩🇰Aarhus, Denmark
Letterkenny University Hospital
🇮🇪Letterkenny, Ireland
Corke University Hospital
🇮🇪Cork, Ireland
APHP Louis Mourier
🇫🇷Colombes, France
Hopital Nord, CHU de Saint Etienne
🇫🇷Saint Etienne, France
The Ottawa Hospital
🇨🇦Ottawa, Canada
Weill Cornell Medicine | NewYork-Presbyterian
🇺🇸New York, New York, United States
Aalborg University Hospital
🇩🇰Aalborg, Denmark
CHU de Clermont - Ferrand
🇫🇷Clermont-Ferrand, France
Hopiteaux de Marseille
🇫🇷Marseille, France
CHU de Nice
🇫🇷Nice, France
APHP Antoine Béclère
🇫🇷Paris, France
CHU de Nîmes
🇫🇷Nîmes, France
APHP Port Royal
🇫🇷Paris, France
CHU de Poitiers
🇫🇷Paris, France
Centra Hospitalier de Roanne
🇫🇷Roanne, France
Flevoziekenhuis
🇳🇱Almere, Netherlands
La Réunion - Saint-Denis
🇫🇷Saint-Denis, France
CHIC de Toulon
🇫🇷Toulon, France
Rotunda Hospital
🇮🇪Dublin, Ireland
CHU de Tours
🇫🇷Tours, France
La Réunion deSt Pierre
🇫🇷Saint-Pierre, France
OLVG oost
🇳🇱Amsterdam, Netherlands
The National Maternity Hospital
🇮🇪Dublin, Ireland
Academic Medical Center
🇳🇱Amsterdam, Noord-Holland, Netherlands
SLAZ
🇳🇱Amsterdam, Netherlands
Jeroen Bosch Ziekenhuis
🇳🇱's-Hertogenbosch, Netherlands
Gelre Ziekenhuizen
🇳🇱Apeldoorn, Netherlands
VU medical center
🇳🇱Amsterdam, Netherlands
Wilhelmina Ziekenhuis
🇳🇱Assen, Netherlands
Amphia ziekenhuis
🇳🇱Breda, Netherlands
Rijnstate hospital
🇳🇱Arnhem, Netherlands
Rode Kruis Ziekenhuis
🇳🇱Beverwijk, Netherlands
Reinier de Graaf Groep
🇳🇱Delft, Netherlands
Bronovo ziekenhuis
🇳🇱Den Haag, Netherlands
HAGA ziekenhuis
🇳🇱Den Haag, Netherlands
Deventer Ziekenhuis
🇳🇱Deventer, Netherlands
Slingeland
🇳🇱Doetinchem, Netherlands
Albert Schweitzer
🇳🇱Dordrecht, Netherlands
Gelderse Vallei
🇳🇱Ede, Netherlands
Admiraal de Ruijter Ziekenhuis
🇳🇱Goes, Netherlands
UMCG
🇳🇱Groningen, Netherlands
Martini Ziekenhuis
🇳🇱Groningen, Netherlands
Groene Hart Ziekenhuis
🇳🇱Gouda, Netherlands
St Jansdal
🇳🇱Harderwijk, Netherlands
Atrium MC
🇳🇱Heerlen, Netherlands
MC Leeuwarden
🇳🇱Leeuwarden, Netherlands
LUMC
🇳🇱Leiden, Netherlands
Canisius-Wilhelmina Ziekenhuis
🇳🇱Nijmegen, Netherlands
TweeSteden
🇳🇱Tilburg, Netherlands
Diakonessen Utrecht
🇳🇱Utrecht, Netherlands
UMCU
🇳🇱Utrecht, Netherlands
Oslo University Hospital
🇳🇴Oslo, Norway
Máxima MC
🇳🇱Veldhoven, Netherlands
Vall d'Hebron Hospital
🇪🇸Barcelona, Spain
Federal State Institution "Research Center for Obstetrics, Gynecology and Perinatology"
🇷🇺Moscow, Russian Federation