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Comparison of Low and Intermediate Dose Low-molecular-weight Heparin to Prevent Recurrent Venous Thromboembolism in Pregnancy

Registration Number
NCT01828697
Lead Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
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
Inclusion Criteria
  • 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).
Exclusion Criteria
  • 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
GroupInterventionDescription
Low dose LMWHFixed low dose tinzaparinFixed 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 LMWHLow dose nadroparinFixed 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 LMWHLow dose enoxaparinFixed 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 LMWHLow dose dalteparinFixed 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 LMWHIntermediate dose nadroparinIntermediate 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 LMWHIntermediate dose enoxaparinIntermediate 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 LMWHIntermediate dose dalteparinIntermediate 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 LMWHIntermediate dose tinzaparinIntermediate 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
NameTimeMethod
Symptomatic confirmed deep venous thrombosisFrom 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 embolismFrom 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
NameTimeMethod
Symptomatic confirmed deep venous thrombosisFrom 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 embolismFrom 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)

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

🇫🇷

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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Weill Cornell Medicine | NewYork-Presbyterian
🇺🇸New York, New York, United States

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