Safety and Efficacy of Therapeutic Anticoagulation With Tinzaparin During Pregnancy Via Weight-based Dosing

Study Overview
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Brief Summary
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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
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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.

Official Title
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Weight-Adjusted Dosing of Tinzaparin in Pregnancy

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Tinzaparin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Women requiring therapeutic anticoagulation, singleton pregnancy,<30weeks | Drug: Tinzaparin<br>* LMWH (tinzaparin-Innohep, Leo Pharma A/S) 175 anti-factor Xa units per kilogram of body weight sub-cutaneously once daily. Treatment will be done for the duration of the pregnancy.<br>* Other names: innohep;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of anti-Xa levels falling outside the target range of 0.4-1.2IU/mL |  | anti-Xa level Day 1,28, then q4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean dosage requirement in each trimester |  | 1 year | 
| rate of clinical outcomes (PE/DVT) - objective testing of DVT/PE from radiology |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticoagulation, pregnancy