NCT04055389

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

Preventing de Novo Portal Vein Thrombosis With Antithrombin-III in Patients With Cirrhosis: A Randomized, Double-blinded, Placebo - Controlled Trial (PiVoT-AC Trial)

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Jonathan Stine · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

PVT is a common complication in patients with cirrhosis, affecting 10% to 25% of patients. PVT is a potentially life-threatening occurrence, complicating transplant candidacy and reducing five-year survival. In addition to the mortality risk posed by PVT, microthrombi within the liver have been linked to decompensation due to the phenomenon of parenchymal extinction. Because of the developing understanding of a baseline hypercoagulable state in many cirrhosis patients, recent studies have demonstrated the benefit of prophylactic anticoagulation with enoxaparin in patients with cirrhosis to prevent PVT. In addition to the benefit in reducing PVT, prophylactic anticoagulation was also found to reduce liver decompensation and improve overall survival. Risk factors for PVT are well described. The strongest independent risk factor for PVT is portal vein velocity. For each 1 cm/s decrease in portal vein velocity, PVT risk increases 16%. Portal vein velocity \<15cm/sec is the best-established cutoff for predicting the development of de novo PVT over the ensuing twelve months. In addition, patients with cirrhosis and venous thromboembolism (PVT, deep vein thrombosis, pulmonary embolus) have abnormally low levels of AT-III. A recent report by the NPB-06 study group suggest that administering intravenous AT-III at dosage of 1500 units/day for five consecutive days in patients with cirrhosis and AT-III \<70% serum level is a safe and effective treatment for PVT with promising short-term partial and complete resolution of PVT. Despite this, the role of AT repletion in preventing PVT remains unknown.

Conditions

• Portal Vein Thrombosis
• Cirrhosis, Liver

Interventions

Type	Name	Description
DRUG	Antithrombin III	Patients with reversal of flow or sluggish flow in the main portal vein (\<15 cm/s by Doppler ultrasound exam) will be enrolled and randomized to either weekly infusions of AT-III (half-life \~4 days) at a weight-based dosage according to the following formula: \[Desired level of AT (100%) - Subject level of AT (%)\] \* subject weight (kg) 1.4 or placebo for 24 weeks of therapy.
OTHER	Placebo	No study drug

Timeline

• Start date: 2021-01-01
• Primary completion: 2022-02-22
• Completion: 2022-02-22
• First posted: 2019-08-13
• Last updated: 2022-03-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study