Back to resultsComparison of Low and Intermediate Dose Low-molecular-weight Heparin to Prevent Recurrent Venous Thromboembolism in Pregnancy (Highlow)
Primary Purpose
Deep Venous Thrombosis, Pulmonary Embolism
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Low dose nadroparin
Intermediate dose nadroparin
Low dose enoxaparin
Intermediate dose enoxaparin
Low dose dalteparin
Intermediate dose dalteparin
Fixed low dose tinzaparin
Intermediate dose tinzaparin
Sponsored by
About this trial
This is an interventional prevention trial for Deep Venous Thrombosis focused on measuring Low-molecular-weight heparin, Pregnancy, Venous thrombosis
Eligibility Criteria
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.
Sites / Locations
- Weill Cornell Medicine | NewYork-Presbyterian
- KU Leuven
- The Ottawa Hospital
- Aalborg University Hospital
- Aarhus University Hospital
- CHU de Besancon
- CHU de Bordeaux
- CHU de Brest
- CHU de Caen
- CHU de Clermont - Ferrand
- APHP Louis Mourier
- CHU de Grenoble
- CHU de Limoges
- Hopiteaux de Marseille
- Marseille St Joseph
- CHU de Nancy
- CHU de Nice
- CHU de Nîmes
- APHP Antoine Béclère
- APHP Port Royal
- CHU de Poitiers
- Centra Hospitalier de Roanne
- Hopital Nord, CHU de Saint Etienne
- La Réunion - Saint-Denis
- La Réunion deSt Pierre
- Polyclinique de Sète
- CHIC de Toulon
- CHU de Tours
- Corke University Hospital
- Coombe Women's Hospital
- Rotunda Hospital
- The National Maternity Hospital
- Letterkenny University Hospital
- University Hospital Limerick
- Academic Medical Center
- Jeroen Bosch Ziekenhuis
- Flevoziekenhuis
- OLVG oost
- SLAZ
- VU medical center
- Gelre Ziekenhuizen
- Rijnstate hospital
- Wilhelmina Ziekenhuis
- Rode Kruis Ziekenhuis
- Amphia ziekenhuis
- Reinier de Graaf Groep
- Bronovo ziekenhuis
- HAGA ziekenhuis
- Deventer Ziekenhuis
- Slingeland
- Albert Schweitzer
- Gelderse Vallei
- Admiraal de Ruijter Ziekenhuis
- Groene Hart Ziekenhuis
- Martini Ziekenhuis
- UMCG
- Spaarne Gasthuis
- St Jansdal
- Atrium MC
- MC Leeuwarden
- LUMC
- MUMC
- Canisius-Wilhelmina Ziekenhuis
- St. Radboud UMC
- Erasmus MC
- TweeSteden
- Diakonessen Utrecht
- UMCU
- Máxima MC
- Oslo University Hospital
- Federal State Institution "Research Center for Obstetrics, Gynecology and Perinatology"
- Vall d'Hebron Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Low dose LMWH
Intermediate dose LMWH
Arm Description
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 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.
Outcomes
Primary Outcome Measures
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.
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)
Secondary Outcome Measures
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.
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)
Full Information
NCT ID
NCT01828697
First Posted
April 5, 2013
Last Updated
May 21, 2022
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Netherlands Organisation for Scientific Research, Aspen Pharma, CHU of Saint Etienne: French Ministry of Health Grant (sponsor of the French part of the study), Rotunda Hospital: Definitive Interventions and Feasibility Awards (DIFA) 2017 (sponsor of the Irish part of the study))
1. Study Identification
Unique Protocol Identification Number
NCT01828697
Brief Title
Comparison of Low and Intermediate Dose Low-molecular-weight Heparin to Prevent Recurrent Venous Thromboembolism in Pregnancy
Acronym
Highlow
Official Title
Low-molecular-weight Heparin to Prevent Recurrent VTE in Pregnancy: a Randomized Controlled Trial of Two Doses
Study Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Completed
Study Start Date
April 24, 2013 (Actual)
Primary Completion Date
October 31, 2021 (Actual)
Study Completion Date
October 31, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Netherlands Organisation for Scientific Research, Aspen Pharma, CHU of Saint Etienne: French Ministry of Health Grant (sponsor of the French part of the study), Rotunda Hospital: Definitive Interventions and Feasibility Awards (DIFA) 2017 (sponsor of the Irish part of the study))
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Deep Venous Thrombosis, Pulmonary Embolism
Keywords
Low-molecular-weight heparin, Pregnancy, Venous thrombosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
1110 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low dose LMWH
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Intermediate dose LMWH
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Low dose nadroparin
Other Intervention Name(s)
nadroparin, Fraxiparin
Intervention Description
Fixed low dose nadroparin:
< 100 kg: 2850 IU subcutaneously once-daily
100 kg and above: 3800 IU subcutaneously once-daily
Intervention Type
Drug
Intervention Name(s)
Intermediate dose nadroparin
Other Intervention Name(s)
nadroparin, Fraxiparin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Low dose enoxaparin
Other Intervention Name(s)
enoxaparin, Clexane
Intervention Description
Fixed low dose enoxaparin:
< 100 kg: 40 mg subcutaneously once-daily
100 kg and above: 60 mg subcutaneously once-daily
Intervention Type
Drug
Intervention Name(s)
Intermediate dose enoxaparin
Other Intervention Name(s)
enoxaparin, Clexane
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Low dose dalteparin
Other Intervention Name(s)
dalteparin, Fragmin
Intervention Description
Fixed low dose dalteparin:
< 100 kg: 5000 IU subcutaneously once-daily
100 kg and above: 7500 IU subcutaneously once-daily
Intervention Type
Drug
Intervention Name(s)
Intermediate dose dalteparin
Other Intervention Name(s)
dalteparin, Fragmin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fixed low dose tinzaparin
Other Intervention Name(s)
tinzaparin, Innohep
Intervention Description
Fixed low dose tinzaparin:
< 100 kg: 3500 IU subcutaneously once-daily
100 kg and above: 4500 IU subcutaneously once-daily
Intervention Type
Drug
Intervention Name(s)
Intermediate dose tinzaparin
Other Intervention Name(s)
tinzaparin, Innohep
Intervention Description
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.
Primary Outcome Measure Information:
Title
Symptomatic confirmed deep venous thrombosis
Description
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
Title
Symptomatic confirmed pulmonary embolism
Description
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
Secondary Outcome Measure Information:
Title
Symptomatic confirmed deep venous thrombosis
Description
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
Title
Symptomatic confirmed pulmonary embolism
Description
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
Other Pre-specified Outcome Measures:
Title
Major bleeding
Description
Major bleeding is defined as overt bleeding and:
Associated with a fall in hemoglobin of 2 g/dL or more, or
Leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or
Occurring in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retro-peritoneal, or
Contributing to death
Time Frame
During pregnancy until 3 months postpartum
Title
Composite of major bleeding and clinically relevant non-major bleeding
Description
See 'Major bleeding' for the definition.
Clinically relevant non-major bleeding is defined as overt bleeding not meeting the criteria for major bleeding but associated with medical intervention, unscheduled contact (visit or telephone call) with a physician, (temporary) cessation of study treatment, or associated with discomfort such as pain, or impairment of activities of daily life.
Hematuria if it is macroscopic, and either spontaneous or lasts for more than 24 hours after instrumentation (e.g. catheter placement or surgery) of the urogenital tract, or
Macroscopic gastro-intestinal haemorrhage: at least one episode of melena/hematemesis, if clinically apparent, or
Rectal blood loss, if more than a few spots, or
Hemoptysis, if more than a few speckles in the sputum, or
Intramuscular hematoma, or
Subcutaneous hematoma if the size is larger than 25 cm2, or larger than 100 cm2 if provoked, or
Multiple source bleeding
Time Frame
During pregnancy until 3 months postpartum
Title
Early postpartum hemorrhage
Description
Postpartum haemorrhage is defined as blood loss of more than 500 mL within 24 hours of delivery (WHO-criteria). Severe postpartum haemorrhage is defined as blood loss of more than 1000 mL within 24 hours of delivery.
Time Frame
Within 24 hours of delivery
Title
Blood transfusion < 6 weeks after delivery
Time Frame
Within 6 weeks of delivery
Title
Blood transfusion < 24 hours postpartum
Time Frame
Within 24 hours of delivery
Title
Late postpartum hemorrhage
Description
Postpartum haemorrhage is defined as blood loss of more than 500 mL within 24 hours of delivery (WHO-criteria). Severe postpartum haemorrhage is defined as blood loss of more than 1000 mL within 24 hours of delivery.
Time Frame
From 24 hours postpartum to 6 weeks postpartum
Title
Mortality
Time Frame
During pregnancy until 3 months postpartum
Title
Minor bleeding
Description
Minor bleeding is defined as all other overt bleeding episodes not meeting the criteria for major or clinically relevant bleeding or postpartum haemorrhage.
Time Frame
During pregnancy until 3 months postpartum
Title
Skin complications
Description
e.g. itching, swelling, pain
Time Frame
During pregnancy until 3 months postpartum
Title
Easy bruising
Time Frame
During pregnancy until 3 months postpartum
Title
Necessity to switch to other LMWH
Time Frame
During pregnancy until 6 weeks postpartum
Title
Heparin-induced thrombocytopenia
Description
Heparin-induced thrombocytopenia is defined according to the criteria of the ACCP guidelines.
Time Frame
During pregnancy until 3 months postpartum
Title
Congenital anomalies or birth defects
Time Frame
During pregnancy until 3 months postpartum
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saskia Middeldorp, MD PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medicine | NewYork-Presbyterian
City
New York
State/Province
New York
Country
United States
Facility Name
KU Leuven
City
Leuven
Country
Belgium
Facility Name
The Ottawa Hospital
City
Ottawa
Country
Canada
Facility Name
Aalborg University Hospital
City
Aalborg
Country
Denmark
Facility Name
Aarhus University Hospital
City
Aarhus
Country
Denmark
Facility Name
CHU de Besancon
City
Besançon
Country
France
Facility Name
CHU de Bordeaux
City
Bordeaux
Country
France
Facility Name
CHU de Brest
City
Brest
Country
France
Facility Name
CHU de Caen
City
Caen
Country
France
Facility Name
CHU de Clermont - Ferrand
City
Clermont-Ferrand
Country
France
Facility Name
APHP Louis Mourier
City
Colombes
Country
France
Facility Name
CHU de Grenoble
City
Grenoble
Country
France
Facility Name
CHU de Limoges
City
Limoges
Country
France
Facility Name
Hopiteaux de Marseille
City
Marseille
Country
France
Facility Name
Marseille St Joseph
City
Marseille
Country
France
Facility Name
CHU de Nancy
City
Nancy
Country
France
Facility Name
CHU de Nice
City
Nice
Country
France
Facility Name
CHU de Nîmes
City
Nîmes
Country
France
Facility Name
APHP Antoine Béclère
City
Paris
Country
France
Facility Name
APHP Port Royal
City
Paris
Country
France
Facility Name
CHU de Poitiers
City
Paris
Country
France
Facility Name
Centra Hospitalier de Roanne
City
Roanne
Country
France
Facility Name
Hopital Nord, CHU de Saint Etienne
City
Saint Etienne
Country
France
Facility Name
La Réunion - Saint-Denis
City
Saint-Denis
Country
France
Facility Name
La Réunion deSt Pierre
City
Saint-Pierre
Country
France
Facility Name
Polyclinique de Sète
City
Sète
Country
France
Facility Name
CHIC de Toulon
City
Toulon
Country
France
Facility Name
CHU de Tours
City
Tours
Country
France
Facility Name
Corke University Hospital
City
Cork
Country
Ireland
Facility Name
Coombe Women's Hospital
City
Dublin
Country
Ireland
Facility Name
Rotunda Hospital
City
Dublin
Country
Ireland
Facility Name
The National Maternity Hospital
City
Dublin
Country
Ireland
Facility Name
Letterkenny University Hospital
City
Letterkenny
Country
Ireland
Facility Name
University Hospital Limerick
City
Limerick
Country
Ireland
Facility Name
Academic Medical Center
City
Amsterdam
State/Province
Noord-Holland
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Jeroen Bosch Ziekenhuis
City
's-Hertogenbosch
Country
Netherlands
Facility Name
Flevoziekenhuis
City
Almere
Country
Netherlands
Facility Name
OLVG oost
City
Amsterdam
Country
Netherlands
Facility Name
SLAZ
City
Amsterdam
Country
Netherlands
Facility Name
VU medical center
City
Amsterdam
Country
Netherlands
Facility Name
Gelre Ziekenhuizen
City
Apeldoorn
Country
Netherlands
Facility Name
Rijnstate hospital
City
Arnhem
Country
Netherlands
Facility Name
Wilhelmina Ziekenhuis
City
Assen
Country
Netherlands
Facility Name
Rode Kruis Ziekenhuis
City
Beverwijk
Country
Netherlands
Facility Name
Amphia ziekenhuis
City
Breda
Country
Netherlands
Facility Name
Reinier de Graaf Groep
City
Delft
Country
Netherlands
Facility Name
Bronovo ziekenhuis
City
Den Haag
Country
Netherlands
Facility Name
HAGA ziekenhuis
City
Den Haag
Country
Netherlands
Facility Name
Deventer Ziekenhuis
City
Deventer
Country
Netherlands
Facility Name
Slingeland
City
Doetinchem
Country
Netherlands
Facility Name
Albert Schweitzer
City
Dordrecht
Country
Netherlands
Facility Name
Gelderse Vallei
City
Ede
Country
Netherlands
Facility Name
Admiraal de Ruijter Ziekenhuis
City
Goes
Country
Netherlands
Facility Name
Groene Hart Ziekenhuis
City
Gouda
Country
Netherlands
Facility Name
Martini Ziekenhuis
City
Groningen
Country
Netherlands
Facility Name
UMCG
City
Groningen
Country
Netherlands
Facility Name
Spaarne Gasthuis
City
Haarlem
Country
Netherlands
Facility Name
St Jansdal
City
Harderwijk
Country
Netherlands
Facility Name
Atrium MC
City
Heerlen
Country
Netherlands
Facility Name
MC Leeuwarden
City
Leeuwarden
Country
Netherlands
Facility Name
LUMC
City
Leiden
Country
Netherlands
Facility Name
MUMC
City
Maastricht
Country
Netherlands
Facility Name
Canisius-Wilhelmina Ziekenhuis
City
Nijmegen
Country
Netherlands
Facility Name
St. Radboud UMC
City
Nijmegen
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
Country
Netherlands
Facility Name
TweeSteden
City
Tilburg
Country
Netherlands
Facility Name
Diakonessen Utrecht
City
Utrecht
Country
Netherlands
Facility Name
UMCU
City
Utrecht
Country
Netherlands
Facility Name
Máxima MC
City
Veldhoven
Country
Netherlands
Facility Name
Oslo University Hospital
City
Oslo
Country
Norway
Facility Name
Federal State Institution "Research Center for Obstetrics, Gynecology and Perinatology"
City
Moscow
Country
Russian Federation
Facility Name
Vall d'Hebron Hospital
City
Barcelona
Country
Spain
12. IPD Sharing Statement
Citations:
PubMed Identifier
10217099
Citation
Greer IA. Thrombosis in pregnancy: maternal and fetal issues. Lancet. 1999 Apr 10;353(9160):1258-65. doi: 10.1016/S0140-6736(98)10265-9.
Results Reference
background
PubMed Identifier
12130523
Citation
Pabinger I, Grafenhofer H, Kyrle PA, Quehenberger P, Mannhalter C, Lechner K, Kaider A. Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism. Blood. 2002 Aug 1;100(3):1060-2. doi: 10.1182/blood-2002-01-0149.
Results Reference
background
PubMed Identifier
18690344
Citation
White RH, Chan WS, Zhou H, Ginsberg JS. Recurrent venous thromboembolism after pregnancy-associated versus unprovoked thromboembolism. Thromb Haemost. 2008 Aug;100(2):246-52.
Results Reference
background
PubMed Identifier
22315276
Citation
Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e691S-e736S. doi: 10.1378/chest.11-2300.
Results Reference
background
PubMed Identifier
15811953
Citation
Greer IA, Nelson-Piercy C. Low-molecular-weight heparins for thromboprophylaxis and treatment of venous thromboembolism in pregnancy: a systematic review of safety and efficacy. Blood. 2005 Jul 15;106(2):401-7. doi: 10.1182/blood-2005-02-0626. Epub 2005 Apr 5.
Results Reference
background
PubMed Identifier
20464719
Citation
Tooher R, Gates S, Dowswell T, Davis LJ. Prophylaxis for venous thromboembolic disease in pregnancy and the early postnatal period. Cochrane Database Syst Rev. 2010 May 12;(5):CD001689. doi: 10.1002/14651858.CD001689.pub2.
Results Reference
background
PubMed Identifier
10365733
Citation
Sanson BJ, Lensing AW, Prins MH, Ginsberg JS, Barkagan ZS, Lavenne-Pardonge E, Brenner B, Dulitzky M, Nielsen JD, Boda Z, Turi S, Mac Gillavry MR, Hamulyak K, Theunissen IM, Hunt BJ, Buller HR. Safety of low-molecular-weight heparin in pregnancy: a systematic review. Thromb Haemost. 1999 May;81(5):668-72.
Results Reference
background
PubMed Identifier
11762651
Citation
Lepercq J, Conard J, Borel-Derlon A, Darmon JY, Boudignat O, Francoual C, Priollet P, Cohen C, Yvelin N, Schved JF, Tournaire M, Borg JY. Venous thromboembolism during pregnancy: a retrospective study of enoxaparin safety in 624 pregnancies. BJOG. 2001 Nov;108(11):1134-40. doi: 10.1111/j.1471-0528.2003.00272.x.
Results Reference
background
PubMed Identifier
15869590
Citation
Pabinger I, Grafenhofer H, Kaider A, Kyrle PA, Quehenberger P, Mannhalter C, Lechner K. Risk of pregnancy-associated recurrent venous thromboembolism in women with a history of venous thrombosis. J Thromb Haemost. 2005 May;3(5):949-54. doi: 10.1111/j.1538-7836.2005.01307.x.
Results Reference
background
PubMed Identifier
21232006
Citation
Roeters van Lennep JE, Meijer E, Klumper FJ, Middeldorp JM, Bloemenkamp KW, Middeldorp S. Prophylaxis with low-dose low-molecular-weight heparin during pregnancy and postpartum: is it effective? J Thromb Haemost. 2011 Mar;9(3):473-80. doi: 10.1111/j.1538-7836.2011.04186.x.
Results Reference
background
PubMed Identifier
21314819
Citation
Lindqvist PG, Bremme K, Hellgren M; Working Group on Hemostatic Disorders (Hem-ARG), Swedish Society of Obstetrics and Gynecology. Efficacy of obstetric thromboprophylaxis and long-term risk of recurrence of venous thromboembolism. Acta Obstet Gynecol Scand. 2011 Jun;90(6):648-53. doi: 10.1111/j.1600-0412.2011.01098.x. Epub 2011 Apr 15.
Results Reference
background
PubMed Identifier
22102641
Citation
Roshani S, Cohn DM, Stehouwer AC, Wolf H, van der Post JA, Buller HR, Kamphuisen PW, Middeldorp S. Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin: results of a retrospective cohort study. BMJ Open. 2011 Nov 14;1(2):e000257. doi: 10.1136/bmjopen-2011-000257. Print 2011.
Results Reference
background
PubMed Identifier
20335572
Citation
Kaandorp SP, Goddijn M, van der Post JA, Hutten BA, Verhoeve HR, Hamulyak K, Mol BW, Folkeringa N, Nahuis M, Papatsonis DN, Buller HR, van der Veen F, Middeldorp S. Aspirin plus heparin or aspirin alone in women with recurrent miscarriage. N Engl J Med. 2010 Apr 29;362(17):1586-96. doi: 10.1056/NEJMoa1000641. Epub 2010 Mar 24.
Results Reference
background
PubMed Identifier
36354038
Citation
Bistervels IM, Buchmuller A, Wiegers HMG, Ni Ainle F, Tardy B, Donnelly J, Verhamme P, Jacobsen AF, Hansen AT, Rodger MA, DeSancho MT, Shmakov RG, van Es N, Prins MH, Chauleur C, Middeldorp S; Highlow Block writing committee; Highlow Investigators. Intermediate-dose versus low-dose low-molecular-weight heparin in pregnant and post-partum women with a history of venous thromboembolism (Highlow study): an open-label, multicentre, randomised, controlled trial. Lancet. 2022 Nov 19;400(10365):1777-1787. doi: 10.1016/S0140-6736(22)02128-6. Epub 2022 Oct 28.
Results Reference
derived
PubMed Identifier
33779986
Citation
Middleton P, Shepherd E, Gomersall JC. Venous thromboembolism prophylaxis for women at risk during pregnancy and the early postnatal period. Cochrane Database Syst Rev. 2021 Mar 29;3(3):CD001689. doi: 10.1002/14651858.CD001689.pub4.
Results Reference
derived
PubMed Identifier
25903529
Citation
Middeldorp S. New studies of low-molecular-weight heparin in pregnancy. Thromb Res. 2015 Feb;135 Suppl 1:S26-9. doi: 10.1016/S0049-3848(15)50436-2. Epub 2015 Feb 9.
Results Reference
derived
PubMed Identifier
24768093
Citation
Bleker SM, Coppens M, Middeldorp S. Sex, thrombosis and inherited thrombophilia. Blood Rev. 2014 May;28(3):123-33. doi: 10.1016/j.blre.2014.03.005. Epub 2014 Apr 1.
Results Reference
derived
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Comparison of Low and Intermediate Dose Low-molecular-weight Heparin to Prevent Recurrent Venous Thromboembolism in Pregnancy
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