Efficacy and Safety of Dabigatran in Patients With Cirrhosis and Portal Vein Thrombosis

Study Overview
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Brief Summary
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A randomized controlled trial to study the efficacy and safety of Dabigatran in Cirrhotic patients who develop PVT.In this study the patients who meet the inclusion criteria will be randomized to either receive Dabigatran or placebo [multivitamin tablet]. Blood samples will be taken &Imaging will be done accordingly to notice progression or recanalization of PVT.The patients are followed up every 2 months up to 18 month .Then statistical analysis will be done to find whether the Dabigatran is efficacious in cirrhotic patients for recanalization of PVT.

Detailed Description
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Study population -All the patients of cirrhosis of liver patients visiting to ILBS and diagnosed to have non tumor portal vein thrombosis will be enrolled in the study. Study Design - A Placebo Controlled Double Blinded RCT In this randomized controlled trial, the patients who satisfy the below inclusion and exclusion criteria will be included and they will be randomized, according to 2 groups (in total 84patients) to receive either Placebo or dabigatran 150 mg BD for 12months. These patients will be admitted to the hospital from OPD or emergency. Study period - 1.5 years from ethics approval Intervention The patients in Group A will receive T. Dabigatran 150 mg twice a day .The patients in Group B will receive placebo [multivitamins] Monitoring and assessment At baseline, a complete history with clinical and physical examination, a record of demographic profile, standard of care biochemical investigations would be done. All included patients will be evaluated with - Etiology of cirrhosis Upper GI endoscopy Haemogram (including reticulocyte count) Coagulogram- PT/INR,APTT,TEG Prothrombotic profile- protein c/protein-s/AT-III/Factor V Leiden mutation/ MTHFR C677T/PROTHROMBIN G20210A/ JAK2 V617F MUTATION / Anticardiolipin Ab. Liver function tests, Renal function tests Alpha fetoprotein/PIVKA II USG abdomen with Doppler study CECT-TP or CEMRI-TP to R/O HCC or angiography when PVT diagnosis doubtful. HVPG+LIVER BIOPSY[optional] Fibro scan Child-Pugh score, MELD Subsequently, patients will be assessed clinically at the baseline and post-treatment every2 months till 18 months Statistical Analysis: The data collected will be analyzed using SPSS ver 22 by standard statistical analysis, were numerical data will be analyzed to find mean, median scores and categorical data will be analyzed using Chi square test and continuous data will be analyzed by student T test and any association will be analyzed by the univariate and multivariate analysis, log regression analysis along with ROC curve will be used and p<0.05 will be considered significant and results will be appropriately tabulated Adverse Effects Hemorrhage - Fatal Major - intracranial, retroperitoneal, intraocular, muscle hematoma Minor TREATMENT IN CASE OF ADVERSE EFFECTS - Withdrawal of drug Stopping rule of study Allergic reactions to drug Severe hemorrhage DIC Progression of PVT after 6 months viral reactivation leading to ACLF, acute hepatitis (viral, drug related, autoimmune flare), sepsis with severe coagulopathy

Official Title
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Efficacy and Safety of Dabigatran in Patients With Cirrhosis and Portal Vein Thrombosis-A Randomized Placebo Controlled Trial

Conditions
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Liver Cirrhosis, Portal Vein Thrombosis

Intervention / Treatment
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* Drug: Dabigatran
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical / radiological /histologic diagnosis of cirrhosis [Childs A&B - CTP<9] Partial / total portal vein thrombosis (chronic) Age- 18-70 years Valid consent Exclusion Criteria: Age > 70 years Presence of active infection (<2 weeks) Use of anticoagulant drugs in the past 10 days Pregnancy HIV positivity Recent (<7 days) transfusion with blood products. History of bleeding in last 42 days HCC / Other malignancy Chronic kidney disease [ CrCl< 30] Drug allergies PVT with cavernoma formation

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DABIGATRAN<br>150mg BD for 12 months | Drug: Dabigatran<br>* T. Dabigatran 150 mg twice a day<br>|
| Placebo Comparator: Placebo<br>Placebo | Other: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with complete recanalization of thrombus in both groups. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with partial recanalization of thrombus in both groups. |  | 1 Year | 
| Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups. |  | 6 months | 
| Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups. |  | 1 year | 
| Improvements in Model for End Stage Liver Disease (MELD) Score in both groups | MELD score ranges from 6 to 40. | 6 months | 
| Improvements in Model for End Stage Liver Disease (MELD) Score in both groups | MELD score ranges from 6 to 40. | 1 Year | 
| Number of participants with prevention of secondary decompensation in both groups |  | 1 Year | 
| Adverse Events in both groups |  | 1 year | 
| To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time). |  | 6 Months | 
| To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time). |  | 12 Months | 
| Number of participants with reduction in clinical complications in patients with PVT in both groups |  | 3 Months | 
| Number of participants with reduction in clinical complications in patients with PVT in both groups |  | 6 Months | 
| Number of participants with reduction in clinical complications in patients with PVT in both groups |  | 12 Months | 
| To study the number of participants developing reoccurrence of PVT after treatment with Dabigatran for 12 months by Ultrasound Doppler of splenoportal venous system. |  | 12 months | 
| To determine predictors for recurrence of PVT in patients with cirrhosis. |  | 1 year | 
| To study the predictors of development of PVT in the population of cirrhosis patients screened who did not have PVT at the initiation of the study, for the development of new PVT over the period of the study |  | 1 year |