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

Sponsor

Air Force Military Medical University, China (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02526303

Collaborator

(none)

Enrollment

Arms

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Cirrhosis Portal Vein Thrombosis Anticoagulation	Drug: Nadroparin Calcium and Warfarin	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Primary Completion Date :

Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Anticoagulation 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 Warfarin (with nadroparin calcium at the first 5 days at least) until recanalization or 1 year
No Intervention: Non-anticoaglated No anticoagulatoin or other treatment for PVT will be used in this group of patients.

Arm

Intervention/Treatment

Experimental: Anticoagulation

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

Warfarin (with nadroparin calcium at the first 5 days at least) until recanalization or 1 year

No Intervention: Non-anticoaglated

No anticoagulatoin or other treatment for PVT will be used in this group of patients.

Outcome Measures

Primary Outcome Measures

Number of Participants With Portal Vein Recanalization as Assessed by Cummulative Rate [2 year]

Secondary Outcome Measures

Number of Participants With Liver Decompensation as Assessed by Cummulative Rate [2]
Number of Participants Who Show Improvement in Child-Pugh score > 2 Points [2 years]
Child-Pugh Scores range from 5 to 15
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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