Anticoagulation Regimens in Pregnant Patients With Prosthetic Heart Valves

Study Overview
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Brief Summary
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Pregnancy is associated with increased risk of thrombosis among women with mechanical prosthetic heart valves.However, the best anticoagulant treatment strategies for pregnant patients with prosthetic heart valves have been controversial. In this study the investigators wanted to identify the most effective and safe regimen among different anticoagulant regimens.

Detailed Description
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Four different anticoagulant treatment regimens for pregnant patients with prosthetic heart valves have been described. In the first arm warfarin is stopped and enoxaparine is started in 1mg/kg dose twice a day which is monitored by weekly anti-Xa levels (between 0.7-1.2) during the first trimester and followed by only warfarin after first trimester. In the second arm, if the patient's warfarin consumption is more than 5 mg before pregnancy, warfarin dose is decreased to 2.5 mg during the first trimester combined with enoxaparine in 1mg/kg dose twice a day; adjusted by measurements of anti-Xa levels (between 0.5-1) weekly until the end of 12th week of pregnancy . In the third arm warfarin dose is decreased to 4 mg during the first trimester combined with enoxaparine given in a similar manner. If the patient's therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the same dose during all the pregnancy in the 4th arm. All patients are followed by serial transesophageal echocardiography performed at 0,3,6 and 9. months of pregnancy. Informed consent is taken from all patients. After delivery the babies are examined by a experinced pediatrician and pediatric cardiologist for any congenital anomalies.

Official Title
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Comparison of Different Anticoagulation Regimens in Pregnant Patients With Prosthetic Heart Valves: A Randomized Clinical Trial

Conditions
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Pregnancy, Heart; Complications, Valve, Prosthesis

Intervention / Treatment
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* Drug: Low Molecular Weight Heparine : Enoxaparine
* Drug: Enoxaparine and 2.5 mg Warfarin
* Drug: Enoxaparine and 4mg Warfarin
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant patients with prosthetic heart valves Exclusion Criteria:

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enoxaparine<br>During first trimester, warfarin is stopped and enoxaparine is started in 1mg/kg dose twice a day. Dose is adjusted according to Anti Factor Xa levels (between 0.7-1.2). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4). | Drug: Low Molecular Weight Heparine : Enoxaparine<br>* During first trimester, warfarin is stopped and enoxaparine is started in 1mg/kg dose twice a day. Dose is adjusted according to Anti Factor Xa levels (between 0.7-1.2). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).<br>* Other names: Clexane;|
| Active Comparator: Enoxaparine and 2.5 mg warfarin<br>If the patient's therapeutic warfarin dose is more than 5 mg before pregnancy, warfarin dose is decreased to 2.5 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1.0). Full dose warfarin is continued after first trimester and dose is regulated according to INR (between 2.5-4) | Drug: Enoxaparine and 2.5 mg Warfarin<br>* If the patient's therapeutic warfarin dose is more than 5 mg before pregnancy, warfarin dose is decreased to 2.5 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4)<br>* Other names: Clexane and 2.5 mg Warfarin;|
| Active Comparator: Enoxaparine and 4 mg warfarin<br>If the patient's warfarin consumption dose is more than 5 mg before pregnancy, warfarin dose is decreased to 4 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4). | Drug: Enoxaparine and 4mg Warfarin<br>* If the patient's warfarin consumption dose is more than 5 mg before pregnancy, warfarin dose is decreased to 4 mg during the first trimester and combined with enoxaparine in 1mg/kg dose twice a day. Enoxaparine dose is adjusted according to anti-factor Xa levels (between 0.5-1). Full dose warfarin is continued after first trimester and dose is regulated according to INR level (between 2.5-4).<br>* Other names: Clexane and 4 mg Warfarin;|
| Active Comparator: Warfarin<br>If the patient's therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the same dose during all the pregnancy and the dose is adjusted according to INR level (between 2.5-4). | Drug: Warfarin<br>* If the patient's therapeutic warfarin dose is less than 5 mg before pregnancy, warfarin is continued in the same dose during all the pregnancy and the dose is adjusted according to INR level (between 2.5-4).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Successful pregnancy | In the absence of fetal and maternal fatal or nonfatal major complications successful pregnancy | 12 month | 
| Maternal Complications | Nonfatal major complication: Ischemic stroke, intracranial hemorrhage, embolism (coronary or peripheral), bleeding requiring transfusion, abortus, placental hemorrhage, Assessment of an increase in thrombus burden more than 50% and/or progression of PVT obstruction by transesophageal echocardiography. Nonfatal minor complication: Bleeding without need for transfusion, TIA. | Participants will be followed during pregnancy and postpartum period, an expected average of 12 months | 
| Fetal Complications | Any congenital anomalia which may be attributed to warfarin or enoxaparine usage during pregnancy | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anticoagulation, Prosthetic Heart Valves, Pregnancy, Warfarin, Thrombosis