Anticoagulation for Non-occlusive Portal Vein Thrombosis in Patients With Liver Cirrhosis

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and efficacy of anticoagulation in the treatment of non-occlusive portal vein thrombosis in patients with liver cirrhosis.

Detailed Description
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Portal vein thrombosis is a common complication of liver cirrhosis, especially at the decompensated or advanced stage. The reported prevalence was 10-25% by ultrasound. The effect of PVT on the natural history of liver cirrhosis is not clear, especially the non-occlusive PVT. According to a recent large prospective study (n=1243), the development of PVT and the progression of liver disease are two separate consequences of a common mechanism. It was hypothesized that the activation of coagulation factors in the cirrhotic liver or the portal venous system is the common mechanism for the progression of liver disease, on the one hand, and the development of PVT on the other. A recent randomized clinical trial has shown that enoxaparin therapy for 48 weeks can prevent disease progression and PVT in patients with Child class B-C cirrhosis. Besides, emerging evidences have shown that 30-50% of patients with cirrhosis and partial PVT can achieve this spontaneous recanalization. So what the role of anticoagulation played in the management of PVT in liver cirrhosis is still contraversal. Anticoagulation therapy was also shown very effective with a high recanalization rate of 42-100%. But this data was mostly derived from retrospective, non-randomized study and no well-designed randomized controlled trial has been conducted to evaluate the safety and efficacy of anticoagulation for non-occlusive PVT.

Official Title
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Anticoagulation for Non-occlusive Portal Vein Thrombosis in Patients With Liver Cirrhosis: a Single Center Prospective Randomized Controlled Trial

Conditions
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Liver Cirrhosis, Portal Vein Thrombosis, Anticoagulation

Intervention / Treatment
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* Drug: Nadroparin Calcium and Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent was obtained liver cirrhosis Non-occlusive portal vein thrombosis No history of variceal bleeding or receive endoscopy or β-blocker for the prevention of patients with G3 or G2 with red marks within 3 months before enrollment No plan for liver transplantation Age between 18 and 70 Child-Pugh score ≤ 11 Exclusion Criteria: Acute PVT Fibrotic cord of PV Isolated splenic vein thrombosis or isolated superior mesenteric vein thrombosis Extensive superior mesenteric vein thrombosis involving the distal part Known coagulation disorder besides liver cirrhosis HCC or other malignant tumor Patients with G2 varices with red mark or G3 but did not underwent any preventive endoscopy or β-blockers Platelet count < 10×109/L Receive contraceptive, anticoagulation or antiplatelet drug Receiving thrombolysis treatment Receiving TIPS or shunting surgery Bleeding tendency Recent gastrointestinal bleeding like digestive ulcer or hemorrhagic stroke Severe portal hypertension，for example, refractory ascite or acute variceal bleeidng Spontaneous bacterial peritonitis Severe cardiovascular disorder, endocrine disorder, or mental disease Major surgery within 6 months History of organ transplantation Pregnancy or breast-feeding History of HIV Poor compliance

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Anticoagulation<br>Drug: Nadroparin Calcium and Warfarin Patients will take warfarin started at a dose of 2.5mg/d and with titration of dose to maintain a target INR of 2-3,along with Nadroparin Calcium 85IU／kg，subcutaneous, q12h,for the first 5 days at least. | Drug: Nadroparin Calcium and Warfarin<br>* Warfarin (with nadroparin calcium at the first 5 days at least) until recanalization or 1 year<br>|
| No Intervention: Non-anticoaglated<br>No anticoagulatoin or other treatment for PVT will be used in this group of patients. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Portal Vein Recanalization as Assessed by Cummulative Rate |  | 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Liver Decompensation as Assessed by Cummulative Rate |  | 2 | 
| Number of Participants Who Show Improvement in Child-Pugh score > 2 Points | Child-Pugh Scores range from 5 to 15 | 2 years | 
| Number of Participants Who Show Improvement in MELD Score > 5 points |  | 2 year | 
| Number of Participants with Improved Stiffness of liver and Spleen as Assessed by Transient Elastography |  | 2 years | 
| Number of Participants with Recurrence of Thrombotic Events as Assessed by Cummulative Rate |  | 2 years | 
| Number of Participants Who still Alive at the end of trial as Assessed by Cummulative Rate |  | 2 years | 
| Relationship between Portal Vein Recanalization and Survival Assessed by Cox's Regression Proportional Hazard Model |  | 2 years | 
| Number of Participants With Major Bleeding as Assessed by Cummulative Rate |  | 2 years |