Apixaban, Warfarin and Aspirin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy（ESAWAAPT）

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

Detailed Description
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After successful screening the cases of cirrhosis of liver irrespective of the etiology who have no portal vein thrombosis will be enrolled. The baseline Doppler parameter will be recorded and the patient will be randomized into apixaban, warfarin or aspirin group. From postoperative day three, patients in apixaban group will receive oral Apixaban 2.5mg bid for six months, patients in warfarin group will receive oral Warfarin 2.5mg qd with titration of dose to maintain a target INR of 2-3 for six months, patients in aspirin group will receive oral Aspirin Enterie Ccoated Tablets 100mg qd for six months. All groups will be along with five days of subcutaneous injection of Low Molecular Weight Heparin and three months of oral Dipyridamole. Every three months the Doppler screening for the occurrence of portal vein thrombus (PVT) or spleno-mesenteric thrombosis will be done for all patients. All groups will receive the therapy for six months irrespective of the Doppler findings in relation to portal vein thrombus occurrence. Then six months monitoring will be done in the three groups as per the primary or secondary outcome.

Official Title
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Efficacy and Safety of Apixaban, Warfarin and Aspirin Anticoagulation for Prevention of Portal Vein Thrombosis in Liver Cirrhotic Patients After Laparoscopic Splenectomy

Conditions
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Cirrhosis, Splenectomy; Status, Venous Thrombosis, Hypertension, Portal

Intervention / Treatment
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* Drug: Apixaban
* Drug: Warfarin
* Drug: Aspirin
* Drug: Dipyridamole
* 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 No 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 Human immunodeficiency virus (HIV) infection

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban 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 Apixaban 2.5mg bid for six months. | Drug: Apixaban<br>* From postoperative day 3, patients will receive oral Apixaban 2.5mg bid for six months.<br>* Other names: ELIQUIS;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;|
| 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 six months 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 six months.<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;|
| Experimental: 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 six months. | Drug: Aspirin<br>* From postoperative day 3, patients will receive oral Aspirin Enterie Ccoated Tablets 100mg qd for six months.<br>* Other names: Acetophen;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;|

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 among oral anticoagulant Apixaban with dipyridamole group, oral Warfarin with dipyridamole group and oral Aspirin with dipyridamole group during the study period |  | Two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportions of patients who will show improvement in Child Pugh (>2 points) in three groups |  | Two years | 
| Proportions of patients who will show improvement in Model for End Stage Liver Disease (MELD)(>4 points) in three groups |  | Two 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 |  | Two years | 
| Proportions of patients who will suffer from hepatocellular carcinoma in three groups. |  | Two years | 
| Overall survival in three groups. |  | Two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cirrhosis, Venous thrombosis, Portal Hypertension, Apixaban, Warfarin, Aspirin, Splenectomy, Laparoscopy