Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Warfarin Anticoagulation are effective and safe in Prevention of Portal Vein Thrombosis in Liver Cirrhotic Patients after Laparoscopic Splenectomy and Azygoportal Disconnection for Portal Hypertension

Detailed Description
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After successful screening the cases of cirrhosis of liver irrespective of the etiology who have non tumor portal vein thrombosis will be enrolled. The baseline Doppler parameter will be recorded and the patient will be randomized into either interventional (warfarin) or control (aspirin) group. From postoperative day 3, patients in interventional (warfarin) group will receive oral Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3 for 1 year, patients in control (aspirin) group will receive oral Aspirin Enterie Ccoated Tablets 100mg qd for 1 year, and both groups will be along with five days of subcutaneous injection of Low Molecular Weight Heparin and three months of oral Dipyridamole. Every 3 months the Doppler screening for the occurrence of portal vein thrombus (PVT) or spleno-mesenteric thrombosis will be done for all patients. Both groups will receive the therapy for one year irrespective of the Doppler findings in relation to portal vein thrombus occurrence. Then one year monitoring will be done in the both groups as per the primary or secondary outcome.

Official Title
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Efficacy and Safety of Warfarin Anticoagulation for Prevention of Portal Vein Thrombosis in Liver Cirrhotic Patients After Laparoscopic Splenectomy and Azygoportal Disconnection for Portal Hypertension

Conditions
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Cirrhosis, Hypertension, Status;Splenectomy, Venous Thrombosis

Intervention / Treatment
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* Drug: Warfarin
* Drug: Dipyridamole
* Drug: Aspirin
* Drug: Low Molecular Weight Heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A clinical, radiological or histologic diagnosis of cirrhosis of any etiology Splenomegaly with secondary hypersplenism Bleeding portal hypertension INo evidence of PVT or spleno-mesenteric thrombosis by ultrasound evaluation and angio-CT Informed consent to participate in the study Exclusion Criteria: Hepatocellular carcinoma or any other malignancy Hypercoagulable state other than the liver disease related DRUGS- oral contraceptives, anticoagulation or anti-platelet drugs Base line INR >2 Child-Pugh grade C Recent peptic ulcer disease History of Hemorrhagic stroke Pregnancy Uncontrolled Hypertension Age>75 yrs Human immunodeficiency virus (HIV) infection

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: Warfarin with dipyridamole<br>From postoperative day 3, patients will receive dipyridamole 25mg tid for three months along with subcutaneous Low Molecular Weight Heparin Calcium injection for first five days and Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3. Intially the INR will be monitored twice weekly with gradual escalation of dose to achieve target INR. After achieving the target INR, this is to be repeated every 4 weeks. The Doppler Ultra Sonography screening will be done every 3 months to assess the occurrence of portal vein thrombus, but the medications will be continue for one year irrespective of the occurrence of portal vein thrombus. | Drug: Warfarin<br>* From postoperative day 3, patients will receive oral Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3 for 1 year.<br>* Other names: PANAWARFIN;Drug: Dipyridamole<br>* From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months.<br>* Other names: Dilaplus;Drug: Low Molecular Weight Heparin<br>* From postoperative day 3, patients will receive subcutaneous injection of Low Molecular Weight Heparin (4100 IU) once daily for first five days.<br>* Other names: Fraxiparine;|
| Active Comparator: Aspirin with dipyridamole<br>From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months along with subcutaneous injection of Low Molecular Weight Heparin (4100 IU) for first five days and Aspirin Enterie Ccoated Tablets 100mg qd for one year. | Drug: Dipyridamole<br>* From postoperative day 3, patients will receive oral dipyridamole 25mg tid for three months.<br>* Other names: Dilaplus;Drug: Aspirin<br>* From postoperative day 3, patients will receive oral Aspirin Enterie Ccoated Tablets 100mg qd for 1 year.<br>* Other names: Acetophen;Drug: Low Molecular Weight Heparin<br>* From postoperative day 3, patients will receive subcutaneous injection of Low Molecular Weight Heparin (4100 IU) once daily for first five days.<br>* Other names: Fraxiparine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of patients who will suffer PVT or spleno-mesenteric thrombosis between oral anticoagulant Warfarin with dipyridamole group and oral Aspirin with dipyridamole group during the study period of 3 year from randomization |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of patients who will show improvement in Child Pugh (>2 points)in both groups |  | 3 years | 
| Proportions of patients who will show improvement in Model for End Stage Liver Disease (MELD)(>4 points)in both groups |  | 3 years | 
| Proportions of patients who will show decrease in hepatic decompensation defined as development of ascites, PSE, portal hypertensive bleeding, jaundice, spontaneous bacterial peritonitis, or systemic infection |  | 3 years | 
| Proportions of patients who will suffer from hepatocellular carcinoma in both groups |  | 3 years | 
| Overall survival in both groups |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, Hypertension, venous thrombosis, Warfarin, Splenectomy, Azygoportal Disconnection, Laparoscopy