TIPPS: Thrombophilia in Pregnancy Prophylaxis Study

NCT00967382 | Completed Phase 3 DMC

• 6 other identifiers: 1999210-01HIND 72,350ISRCTN 87441504CIHR 200602MCT-157533-RFATrial number 2004/2442007-000284-21
• Study Type: interventional
• Target: 292
• Locations: 2 countries
• Sites: 12

Brief Summary

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?

Conditions

Pregnancy; Thrombophilia; Pregnancy Complications

Keywords

Pregnancy; Thrombophilia; High-risk pregnancy; LMWH prophylaxis; Placenta mediated pregnancy complications

Outcome Measures

Primary Outcomes (1)

• 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)

  6 weeks post-partum

Secondary Outcomes (3)

• Identify if prophylactic LMWH will reduce rates of pregnancy induced hypertension (PIH), preterm labor and abruptio placenta in pregnant thrombophilic women compared to control

  6 weeks post-partum

• Determine the safety of LMWH use in pregnancy (Specifically rates of bleeding, thrombocytopenia and fractures)

  6 weeks post-partum

• Identify whether prolonged use of LMWH in pregnancy results in decreased bone mineral density (BMD) compared to control

  6 weeks post-partum

Study Arms (2)

Control

NO INTERVENTION

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

dalteparin sodium

ACTIVE COMPARATOR

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

Interventions

dalteparin sodium DRUG

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

Also known as: Fragmin

dalteparin sodium

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (12)

Saint Louis University

St Louis, Missouri, 63117, United States

Location

University of Utah Health Sciences Centre

Salt Lake City, Utah, 84132, United States

Location

Royal Alexandra Hospital

Edmonton, Alberta, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Location

Hamilton Health Sciences Centre

Hamilton, Ontario, Canada

Location

The Ottawa Hospital, Civic Campus

Ottawa, Ontario, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, Canada

Location

Women's College Health Sciences Centre

Toronto, Ontario, Canada

Location

SMBD Jewish General Hospital

Montreal, Quebec, Canada

Location

St Mary's Hospital Centre

Montreal, Quebec, Canada

Location

CHA, Hopital Enfant Jesus

Québec, Quebec, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, Canada

Location

Related Publications (3)

• 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.

  PMID: 33779986 DERIVED

• Rodger MA, Hague WM, Kingdom J, Kahn SR, Karovitch A, Sermer M, Clement AM, Coat S, Chan WS, Said J, Rey E, Robinson S, Khurana R, Demers C, Kovacs MJ, Solymoss S, Hinshaw K, Dwyer J, Smith G, McDonald S, Newstead-Angel J, McLeod A, Khandelwal M, Silver RM, Le Gal G, Greer IA, Keely E, Rosene-Montella K, Walker M, Wells PS; TIPPS Investigators. Antepartum dalteparin versus no antepartum dalteparin for the prevention of pregnancy complications in pregnant women with thrombophilia (TIPPS): a multinational open-label randomised trial. Lancet. 2014 Nov 8;384(9955):1673-83. doi: 10.1016/S0140-6736(14)60793-5. Epub 2014 Jul 24.

  PMID: 25066248 DERIVED

• Bennett SA, Bagot CN, Arya R. Pregnancy loss and thrombophilia: the elusive link. Br J Haematol. 2012 Jun;157(5):529-42. doi: 10.1111/j.1365-2141.2012.09112.x. Epub 2012 Mar 26.

  PMID: 22449204 DERIVED

Related Links

• The Ottawa Hospital Research Institute is the sponsor for TIPPS. This site provides information about the lead institution and provides a link the to coordinating centre located within the thrombosis program.
• Site of the Canadian Institutes of Health Research - information regarding the terms of reference related to the TIPPS grant can be found herein.

MeSH Terms

Conditions

Thrombophilia; Pregnancy Complications

Interventions

Dalteparin

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Marc A Rodger, MD

  Ottawa Hospital Research Institute, Ottawa, Canada

  PRINCIPAL INVESTIGATOR

• William Hague, MD

  Women's and Children's Hospital, Adelaide, Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2009
• First Posted: August 27, 2009
• Study Start: July 1, 2000
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 19, 2014

Record last verified: 2014-05

Locations

CA (10); US (2)