Efficacy and Safety of Rivaroxaban in Acute Non-neoplastic Portal Vein Thrombosis in HCV

Efficacy and Safety of Rivaroxaban in the Management of Acute Non-neoplastic Portal Vein Thrombosis in HCV Related Compensated Cirrhosis

Portal vein thrombosis (PVT) in patients with liver cirrhosis may be due to neoplastic growth or non-neoplastic causes.

• Treating PVT with anticoagulation in liver cirrhosis is difficult to be established but may be of great benefit in acute symptomatic PVT.
• The ultimate goal is complete recanalization of the portal vein without inducing major bleeding, abnormal liver function tests or increased mortality.

Study Overview

• Status: Completed
• Conditions: Portal Vein Thrombosis
• Intervention / Treatment: Drug: Rivaroxaban; Other: symptomatic therapy for ascites, abdominal pain

Detailed Description

Out of 220 patients with chronic HCV who had undergone splenectomy due to hypersplenism in the period extending from May 2014 until August 2016; 36 participants (16.4%) were selected. They were presented with acute PVT. Also, the investigators enrolled 4 patients who were presented with PVT due to portal pyemia complicated infected thrombosed internal piles (n=1), appendicular abscess (n=1), ulcerative colitis (n=2).

Control group It included 30 patients who had acute non-neoplastic PVT with the same inclusion criteria and were given symptomatic therapy for ascites, abdominal pain and followed synchronously with the study group.

Laboratory investigations They included investigation preliminary to splenectomy as liver function tests, coagulation profile, renal function tests, complete blood count, reticulocyte count and bone marrow aspiration. For each patient, Child-Pugh (CTP) and MELD scores were calculated.

Abdominal Ultrasonography (USG) Cirrhotic echo pattern, criteria of portal hypertension, ascites, HCC were excluded Color Doppler Sonography to confirm the diagnosis of PVT. Upper GI Endoscopy All the patients before splenectomy were exposed to upper GI endoscopy to detect the presence and grading of gastro-esophageal varices.

Protocol of therapy Enoxaparin was initiated at a dose of 1mg/kg every 12 hours subcutaneously for 3 days then treatment was continued with rivaroxaban 10mg/12 hr. Rivaroxaban was started 2 hours before the next dose of enoxaparin.

• Follow up every week with a questionnaire about symptoms of bleeding (hematemesis, melena, epistaxis, gum bleeding, vaginal bleeding, subcutaneous bleeding), worsening or improvement of abdominal pain.
• Bedside ultrasonography for detection of thrombus resolution and presence or improvement of ascites every 2 weeks Laboratory follow-up which included serum creatinine, complete blood count, and liver function tests to detect if there any side effects of the therapy every 2 weeks.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute non-neoplastic portal vein thrombosis
• Compensated cirrhosis (Child class A-B)
• The onset of PVT is within 1 week.

Exclusion Criteria:

• Decompensated liver disease
• Bleeding tendency or recent bleeding event as bleeding peptic ulcer or oesophageal varices
• Neoplastic invasion of the portal vein
• Renal impairment with the creatinine clearance ≤ 30 ml/min
• Pregnancy and breastfeeding
• Hypersensitivity to rivaroxaban
• Concomitant treatment with another anticoagulant
• Concomitant use of clopidogrel.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: study group; acute non-neoplastic PVT, compensated cirrhosis, acute PVT onset within 1 week after initial diagnosis - treated with rivaroxaban	Drug: Rivaroxaban; Rivaroxaban 10 mg/12 hour
Placebo Comparator: control group; acute non-neoplastic PVT, compensated cirrhosis, acute PVT onset within 1 week after initial diagnosis receive placebo	Other: symptomatic therapy for ascites, abdominal pain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete recanalization of the portal vein	bedside ultrasonography for detection of thrombus resolution	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
major bleeding	Questionnaire about symptoms of bleeding (hematemesis, melena, epistaxis, gum bleeding, vaginal bleeding, subcutaneous bleeding)	6 months
Hepatotoxicity	liver function tests as AST, ALT (IU/L), total bilirubin (mg/dl)	6 MONTHS

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
short term survival	impact of treating portal vein thrombosis on short term survival	1 year

Collaborators and Investigators

• Sponsor: Zagazig University

Publications and helpful links

General Publications

• Hanafy AS, Abd-Elsalam S, Dawoud MM. Randomized controlled trial of rivaroxaban versus warfarin in the management of acute non-neoplastic portal vein thrombosis. Vascul Pharmacol. 2019 Feb;113:86-91. doi: 10.1016/j.vph.2018.05.002. Epub 2018 Jun 7.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: May 26, 2017
• First Submitted That Met QC Criteria: June 27, 2017
• First Posted (Actual): June 28, 2017

Study Record Updates

• Last Update Posted (Actual): June 28, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: acute; thrombosis; rivaroxaban; Portal vein
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 3779

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No