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

Liver Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04433481
• Other study ID #: ILBS-Cirrhosis-30
• Status: Recruiting
• Phase: N/A
• Start date: June 20, 2020
• Est. completion date: May 31, 2022

Study information

• Verified date: August 2021
• Source: Institute of Liver and Biliary Sciences, India
• Contact: Dr G. Srinivasa Reddy, MD
• Phone: 01146300000
• Email: srinivasareddygolamari[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 84
• Est. completion date: May 31, 2022
• Est. primary completion date: May 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Portal Vein Thrombosis
• Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Dabigatran
T. Dabigatran 150 mg twice a day

Other:
• Placebo
placebo

Locations

Country	Name	City	State
India	Institute of Liver & Biliary Sciences	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Liver and Biliary Sciences, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with complete recanalization of thrombus in both groups.		1 year
Secondary	Number of participants with partial recanalization of thrombus in both groups.		1 Year
Secondary	Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups.		6 months
Secondary	Number of participants with improvements in Child-Turcotte-Pugh (CTP) in both groups.		1 year
Secondary	Improvements in Model for End Stage Liver Disease (MELD) Score in both groups	MELD score ranges from 6 to 40.	6 months
Secondary	Improvements in Model for End Stage Liver Disease (MELD) Score in both groups	MELD score ranges from 6 to 40.	1 Year
Secondary	Number of participants with prevention of secondary decompensation in both groups		1 Year
Secondary	Adverse Events in both groups		1 year
Secondary	To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time).		6 Months
Secondary	To study the changes in coagulation parameters by ROTEM(Rotational Thrombo Elastometry) analysis which includes CFT(clot formation time).		12 Months
Secondary	Number of participants with reduction in clinical complications in patients with PVT in both groups		3 Months
Secondary	Number of participants with reduction in clinical complications in patients with PVT in both groups		6 Months
Secondary	Number of participants with reduction in clinical complications in patients with PVT in both groups		12 Months
Secondary	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
Secondary	To determine predictors for recurrence of PVT in patients with cirrhosis.		1 year
Secondary	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