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

• Sponsor: Institute of Liver and Biliary Sciences, India (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04433481
• Collaborator: (none)
• Enrollment: 84
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 23.3
• Patients Per Site Per Month: 3.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Liver Cirrhosis; Portal Vein Thrombosis	Drug: Dabigatran; Other: Placebo	N/A

Detailed Description

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 -

1. Etiology of cirrhosis

2. Upper GI endoscopy

3. Haemogram (including reticulocyte count)

4. Coagulogram- PT/INR,APTT,TEG

5. Prothrombotic profile- protein c/protein-s/AT-III/Factor V Leiden mutation/ MTHFR C677T/PROTHROMBIN G20210A/ JAK2 V617F MUTATION / Anticardiolipin Ab.

6. Liver function tests, Renal function tests

7. Alpha fetoprotein/PIVKA II

8. USG abdomen with Doppler study

9. CECT-TP or CEMRI-TP to R/O HCC or angiography when PVT diagnosis doubtful.

10. HVPG+LIVER BIOPSY[optional]

11. Fibro scan

12. 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

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 84 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Dabigatran in Patients With Cirrhosis and Portal Vein Thrombosis-A Randomized Placebo Controlled Trial
• Actual Study Start Date: Jun 20, 2020
• Anticipated Primary Completion Date: May 31, 2022
• Anticipated Study Completion Date: May 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DABIGATRAN 150mg BD for 12 months	Drug: Dabigatran; T. Dabigatran 150 mg twice a day
Placebo Comparator: Placebo Placebo	Other: Placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Number of participants with complete recanalization of thrombus in both groups. [1 year]

Secondary Outcome Measures

1. Number of participants with partial recanalization of thrombus in both groups. [1 Year]

2. Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups. [6 months]

3. Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups. [1 year]

4. Improvements in Model for End Stage Liver Disease (MELD) Score in both groups [6 months]

   MELD score ranges from 6 to 40.

5. Improvements in Model for End Stage Liver Disease (MELD) Score in both groups [1 Year]

   MELD score ranges from 6 to 40.

6. Number of participants with prevention of secondary decompensation in both groups [1 Year]

7. Adverse Events in both groups [1 year]

8. To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time). [6 Months]

9. To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time). [12 Months]

10. Number of participants with reduction in clinical complications in patients with PVT in both groups [3 Months]

11. Number of participants with reduction in clinical complications in patients with PVT in both groups [6 Months]

12. Number of participants with reduction in clinical complications in patients with PVT in both groups [12 Months]

13. 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]

14. To determine predictors for recurrence of PVT in patients with cirrhosis. [1 year]

15. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Clinical / radiological /histologic diagnosis of cirrhosis [Childs A&B - CTP<9]

2. Partial / total portal vein thrombosis (chronic)

3. Age- 18-70 years

4. Valid consent

Exclusion Criteria:

1. Age > 70 years

2. Presence of active infection (<2 weeks)

3. Use of anticoagulant drugs in the past 10 days

4. Pregnancy

5. HIV positivity

6. Recent (<7 days) transfusion with blood products.

7. History of bleeding in last 42 days

8. HCC / Other malignancy

9. Chronic kidney disease [ CrCl< 30]

10. Drug allergies

11. PVT with cavernoma formation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Institute of Liver & Biliary Sciences	New Delhi	Delhi	India	110070

Sponsors and Collaborators

• Institute of Liver and Biliary Sciences, India

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Institute of Liver and Biliary Sciences, India
• ClinicalTrials.gov Identifier: NCT04433481
• Other Study ID Numbers: ILBS-Cirrhosis-30
• First Posted: Jun 16, 2020
• Last Update Posted: Aug 25, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Liver Cirrhosis; Thrombosis; Venous Thrombosis; Fibrosis; Dabigatran

Study Results

No Results Posted as of Aug 25, 2021