TIPPS: Thrombophilia in Pregnancy Prophylaxis Study

This study has been completed.
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT00967382
First received: May 29, 2009
Last updated: May 16, 2014
Last verified: May 2014
  Purpose

The TIPPS trial seeks to determine the safety and effectiveness of low-molecular-weight heparin (LMWH), an anticoagulant, in preventing placenta mediated pregnancy complications and venous thromboembolism (VTE) in women with thrombophilia. Thus, the principal research question is: can LMWH prevent thrombosis in the leg veins, pulmonary arteries and placental vessels, thereby reducing the risk of deep vein thrombosis, pulmonary embolism (PE), intrauterine growth restriction (IUGR), preeclampsia, miscarriage and stillbirth?


Condition Intervention Phase
Pregnancy
Thrombophilia
Pregnancy Complications
Drug: dalteparin sodium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: TIPPS - Thrombophilia in Pregnancy Prophylaxis Study: A Multicentre, Multinational, Randomized Control Trial of Prophylaxis Low Molecular Weight Heparin (LMWH) in High-risk Thrombophilic Women.

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • The primary objective of the study is to identify if LMWH prophylaxis in thrombophilic pregnant women results in a greater than 33% relative risk reduction in the composite outcome measure (VTE, pre-eclampsia, IUGR and fetal loss) [ Time Frame: 6 weeks post-partum ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Identify if prophylactic LMWH will reduce rates of pregnancy induced hypertension (PIH), preterm labor and abruptio placenta in pregnant thrombophilic women compared to control [ Time Frame: 6 weeks post-partum ] [ Designated as safety issue: No ]
  • Determine the safety of LMWH use in pregnancy (Specifically rates of bleeding, thrombocytopenia and fractures) [ Time Frame: 6 weeks post-partum ] [ Designated as safety issue: Yes ]
  • Identify whether prolonged use of LMWH in pregnancy results in decreased bone mineral density (BMD) compared to control [ Time Frame: 6 weeks post-partum ] [ Designated as safety issue: Yes ]

Enrollment: 292
Study Start Date: July 2000
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Control

Subjects randomized to control will receive identical obstetrical care and follow-up, but not antenatal dalteparin.

Within 24 hours of delivery, all subject's, regardless of randomization allocation will receive dalteparin sodium 5,000 IU s.c. daily for 6 weeks post-partum

Active Comparator: dalteparin sodium

Subjects randomized to the treatment group will receive daily injections of dalteparin during the antenatal period. They will be taught how to self-administer sub-cutaneous injections of dalteparin 5000 IU once daily (o.d.) until gestational age 20, then twice daily (bid) until 37 weeks gestation or onset of labour.

Within 24 hours of delivery, all subject's, regardless of randomization allocation will receive dalteparin sodium 5,000 IU s.c. daily for 6 weeks post-partum

Drug: dalteparin sodium

Subject's randomize to treatment arm will receive dalteparin sodium 5,000 IU s.c. daily starting on randomization day until 20 weeks gestational age then;

dalteparin sodium 5,000 IU s.c. bid from 20 weeks to onset of labour or 37 weeks gestation (discontinued at the discretion of the investigator/obstetrician)

Within 24 hours of delivery, all subject's, regardless of randomization allocation will receive dalteparin sodium 5,000 IU s.c. daily for 6 weeks post-partum

Other Name: Fragmin

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

One or more of the following:

  • Previous preeclampsia
  • Previous unexplained intra-uterine growth restriction
  • Previous recurrent miscarriage:

    • three(3) or more unexplained miscarriage at less than 10 weeks gestation;
    • two (2) or more unexplained fetal loss between 10 and 16 weeks gestation;
    • one (1) or more unexplained fetal loss at or greater than 16 weeks gestation
  • Previous abruptio placenta
  • Previous personal history of VTE:

    • Previous documented secondary proximal VTE,
    • Previous documented calf-vein thrombosis (idiopathic or secondary),
    • Previous superficial phlebitis
  • First degree relative with symptomatic thrombophilia
  • Pregnancy - > 4weeks gestation and < 20 weeks gestation
  • Thrombophilia:
  • Two abnormal tests, and no normal tests

    • 3.1 Protein S
    • 3.2 Protein C
    • 3.3 Antithrombin
  • Two positive tests

    • 3.4 Anticardiolipin immunoglobulin M (IgM) (>30 U/ml)
    • 3.5 Anticardiolipin immunoglobulin G (IgG) (>30 U/ml)
    • 3.6 Anti-b2 glycoprotein IgG (>20 U/ml)
    • 3.7 Anti-b2 glycoprotein IgM (>20 U/ml)
    • 3.8 Lupus anticoagulant
  • One positive test

    • 3.9 Factor V Leiden (heterozygous or homozygous)
    • 3.10Prothrombin gene defect (heterozygous or homozygous)

Exclusion Criteria:

  • Less than 4 weeks gestation or greater than 20 weeks gestation
  • No confirmed thrombophilia
  • Contraindication to heparin therapy

    • History of heparin induced thrombocytopenia
    • Platelet count less than 100,000 109/L
    • History of osteoporosis or steroid use
    • Actively bleeding
    • Documented peptic ulcer within 6 weeks
    • Heparin, bisulfite or fish allergy
    • Severe hypertension (Systolic Blood Pressure >200mmhg and/or Diastolic Blood Pressure >120mmHg)
    • Serum creatinine greater than 80 umol/L (1.3mg/dl) and an abnormal 24 hour urine creatine clearance (<30ml/min)
    • Severe hepatic failure (INR >1.8)
  • Geographic inaccessibility
  • Need for anticoagulants, discretion of the investigator such as but not limited to:

    • Recurrent fetal loss and phospholipid antibody syndrome
    • Prior idiopathic proximal VTE:
    • History of idiopathic deep venous thrombosis (DVT) or pulmonary embolism (PE) treated with anticoagulants (> 1 month of heparin or warfarin) or inferior vena cava (IVC) interruption;
    • Idiopathic is a VTE occurring outside all of the following periods: antepartum, postpartum, oral contraceptive use, surgery, immobilization, cast, and malignancy
    • Mechanical heart valve
  • Legal lower age limitations (country specific)
  • Prior participation in TIPPS
  • Unable/unwilling to provide informed consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00967382

Locations
United States, Missouri
Saint Louis University
Saint Louis, Missouri, United States, 63117
United States, Utah
University of Utah Health Sciences Centre
Salt Lake City, Utah, United States, 84132
Canada, Alberta
Royal Alexandra Hospital
Edmonton, Alberta, Canada
Canada, Nova Scotia
QEII Health Sciences Centre
Halifax, Nova Scotia, Canada
Canada, Ontario
Hamilton Health Sciences Centre
Hamilton, Ontario, Canada
The Ottawa Hospital, Civic Campus
Ottawa, Ontario, Canada
Women's College Health Sciences Centre
Toronto, Ontario, Canada
Mount Sinai Hospital
Toronto, Ontario, Canada
Canada, Quebec
SMBD Jewish General Hospital
Montreal, Quebec, Canada
St Mary's Hospital Centre
Montreal, Quebec, Canada
Canada, Saskatchewan
Royal University Hospital
Saskatoon, Saskatchewan, Canada
Canada
CHA, Hopital Enfant Jesus
Quebec, Canada
Sponsors and Collaborators
Ottawa Hospital Research Institute
Canadian Institutes of Health Research (CIHR)
Investigators
Principal Investigator: Marc A Rodger, MD Ottawa Hospital Research Institute, Ottawa, Canada
Principal Investigator: William Hague, MD Women's and Children's Hospital, Adelaide, Australia
  More Information

Additional Information:
No publications provided by Ottawa Hospital Research Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT00967382     History of Changes
Other Study ID Numbers: 1999210-01H, IND 72,350, ISRCTN 87441504, CIHR 200602MCT-157533-RFA, Trial number 2004/244, 2007-000284-21
Study First Received: May 29, 2009
Last Updated: May 16, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada

Keywords provided by Ottawa Hospital Research Institute:
Pregnancy
Thrombophilia
High-risk pregnancy
LMWH prophylaxis
Placenta mediated pregnancy complications

Additional relevant MeSH terms:
Pregnancy Complications
Thrombophilia
Hematologic Diseases
Dalteparin
Heparin, Low-Molecular-Weight
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on October 19, 2014