Clinical trial NCT00851864: Safety and Efficacy of Therapeutic Anticoagulation With Tinzaparin During Pregnancy Via Weight-based Dosing
Official title: Weight-Adjusted Dosing of Tinzaparin in Pregnancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Venous Thromboembolism
Keywords: anticoagulation
pregnancy
Lead sponsor: University of Calgary
Sponsor class: OTHER
Collaborators: name: LEO Pharma
First posted: 2009-02-26
Enrollment: 13
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: The purpose of this study is to evaluate the safety and efficacy of therapeutic anticoagulation with tinzaparin during pregnancy via weight-based dosing.

Detailed description: Physicians in the Calgary Health Region are using tinzaparin (predominantly) and other low molecular weight heparins (LMWHs) for the treatment venous thromboembolism (VTE) in pregnancy. The most recent anticoagulation guidelines from American College of Chest Physicians (ACCP) suggest that heparin levels (anti-Factor-Xa activity levels) may be done periodically through pregnancy to determine the need to adjust the dose of LMWH as pregnancy progresses. This monitoring is widely practiced. There is no clear consensus in the literature, however, with some experts suggesting that initial and subsequent dosing may be done based on weight alone (as is done in the non-pregnant population). Given the multiple physiologic changes which occur to drug metabolism during pregnancy, this bears further evaluation. To date, there is very limited data on weight-adjusted dosing of LMWH in pregnancy. This study is therefore designed to determine if dosing of tinzaparin during pregnancy based on weight, with periodic weight-based adjustments, will result in adequate therapeutic anticoagulation.

Eligibility criteria: Inclusion Criteria:

* Singleton pregnancies in women over the age of 18 requiring anticoagulation for acute VTE (DVT/PE), or high-risk prophylaxis at a tinzaparin dose of 175 IU/kg.
* High-risk patients include those with multiple (two or more) episodes of VTE and/or women receiving long-term anticoagulants (e.g. single event with known thrombophilia; APLAs and history of venous thrombosis)

Exclusion Criteria:

* Multiple gestation\\
* Prosthetic valves
* Active bleeding or other contraindication to anticoagulation therapy
* Allergy to heparin, bisulfites, or fish, history of HIT (heparin induced thrombocytopenia), severe hypertension (diastolic \>130)
* Severe hepatic or renal failure
* Patients over 100kg.

Primary outcomes:
measure: Rate of anti-Xa levels falling outside the target range of 0.4-1.2IU/mL
timeFrame: anti-Xa level Day 1,28, then q4 weeks
Secondary outcomes:
measure: mean dosage requirement in each trimester
timeFrame: 1 year
measure: rate of clinical outcomes (PE/DVT) - objective testing of DVT/PE from radiology
timeFrame: 1 year
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Calgary Health Region
state: Alberta
Study officials:
affiliation: University of Calgary
name: Paul Gibson, M.D. FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Calgary
name: Kendra Newell, M.D.
role: STUDY_CHAIR
affiliation: University of Calgary
name: David Sam, M.D. FRCPC
role: STUDY_CHAIR
References:
citation: Gibson PS, Newell K, Sam DX, Mansoor A, Jiang X, Tang S, Ross S. Weight-adjusted dosing of tinzaparin in pregnancy. Thromb Res. 2013 Feb;131(2):e71-5. doi: 10.1016/j.thromres.2012.11.018. Epub 2012 Dec 13.