Preventing de Novo Portal Vein Thrombosis With Antithrombin-III in Patients With Cirrhosis

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: All

Summary

To prevent portal vein thrombosis (PVT) in patients with cirrhosis at risk for PVT by pharmacologic prophylaxis with intravenous antithrombin (AT-III).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jonathan Stine
• Collaborator: Grifols Therapeutics LLC
• Treatments: Antithrombin III; Antithrombins

Criteria

Inclusion criteria:

Cirrhosis documented by:

• Liver biopsy OR

• Clinical, imaging, and laboratory findings consistent with cirrhosis AND

• Disease process etiologic for cirrhosis (e.g., chronic viral hepatitis, non-alcoholic steatohepatitis, history of alcohol abuse, cholestatic liver disease)

• Flow in main portal vein less than 15 cm/sec or reversal of flow as assessed by Doppler ultrasonography

• Age greater than or equal to 18 and less than or equal to 75 years

• AT-III <70%

• Platelet count greater than or equal to 55,000 per uL

• Laboratories reflective of general health status (normal):

• White blood cell count (4-10.4 K/uL)

• Hemoglobin (11.7-15.0 g/dL) and hematocrit (35-44%)

• Creatinine (0.60-1.00 mg/dL) • Child Pugh Turcotte (CPT) Class A cirrhosis

3.2 Exclusion Criteria

• Allergy to AT-III or one of its ingredients

• CPT Class B or C cirrhosis

• Coagulopathy as indicated by International Normalized Ratio (INR) >= 2.2 or an inherited coagulation disorder

• Active hepatitis C infection expecting to initiate HCV therapy within the next two years

• Established PVT or cavernoma

• Transvenous portosystemic shunt (TIPS) placement

• Previous liver transplantation

• Increased risk of bleeding:

• Active pathological bleeding including subjects with actively bleeding esophageal varices

• History of intracranial bleeding

• Unexplained gastrointestinal bleeding

• Subjects with large esophageal varices, or varices with endoscopic stigmata of bleeding (e.g., red wale sign)

• Subjects with gastric or intestinal varices

• Subjects who are taking medicines that increase the risk of thrombosis (e.g. tamoxifen)

• Subjects with any clinically significant bleeding within the last one month

• Need for therapeutic anticoagulation for another indication

• Concurrent use of antiplatelet medications excluding aspirin 81 mg once daily as aspirin at this dosage does not increase bleeding when given concomitantly with AT-III

• Pregnancy or breastfeeding

• Recent major surgery within six weeks

• Inability or unwilling to give informed consent

• Hepatocellular carcinoma [diagnosed by cross-sectional imaging, e.g., computed tomography (CT) or magnetic resonance imaging (MRI)] or another active malignancy

• Predicted lifespan less than two years

• Severe concurrent disease threatening successful completion of the trial in the opinion of the study principle investigator

• Ongoing substance abuse as judged by the study principal investigator and confirmed by an eight-panel urine drug test at screening

• Significant alcohol consumption (20g/day for women and 30g/day for men)

• Human Immunodeficiency Virus infection

• Worsening liver function based on the two initial laboratory values used to establish baseline laboratory measurements (section 7.2.2 Monitoring and Intervention Plan for Drug-induced Liver Injury)