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

Venous Thromboembolism Clinical Trial

Official title:

Weight-Adjusted Dosing of Tinzaparin in Pregnancy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00851864
• Other study ID #: 05161977
• Status: Completed
• Phase: Phase 4
• First received: November 18, 2008
• Last updated: August 14, 2013
• Start date: October 2007
• Est. completion date: May 2011

Study information

• Verified date: August 2013
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health CanadaCanada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: May 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Tinzaparin
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.

Locations

Country	Name	City	State
Canada	Calgary Health Region	Calgary	Alberta

Sponsors (2)

Lead Sponsor	Collaborator
University of Calgary	LEO Pharma

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	mean dosage requirement in each trimester		1 year	No
Secondary	rate of clinical outcomes (PE/DVT) - objective testing of DVT/PE from radiology		1 year	Yes