Placebo-controlled Study of NPB-06 in Patients With Portal Vein Thrombosis

Patients with portal vein thrombosis, who have chronic liver diseases especially liver cirrhosis associated with low levels of AT III, will receive intravenous injection of NPB-06 or placebo. The superiority of NPB-06 to placebo as anticoagulative agent will be verified in a randomized, double-blind, parallel-assignment design based on the proportion of patients obtained complete recanalization or partial recanalization of portal vein thrombosis.

The safety of NPB-06 will be evaluated based on adverse events and adverse drug reactions (ADRs) observed between administration and 21 days after administration in comparison with the placebo group.

Study Overview

• Status: Completed
• Conditions: Portal Vein Thrombosis
• Intervention / Treatment: Drug: NPB-06; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chubu, Japan
  • Hokkaido, Japan
  • Kanto, Japan
  • Kyushu, Japan
  • Osaka, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Inpatients or outpatients meet the criteria (1)-(4) below will be enrolled in the study. Patients have to provide written informed consent for voluntary participation in the study.

1. Patients who the serum level of AT-III is 70% or less
2. Patients with portal vein thrombosis detected by ultrasonography
3. Patients who have more than 50% of the thrombus lumen occupancy
4. Patients who are older than 20 years at the time of consent

Exclusion Criteria:

Patients who meet any of the following criteria will be excluded from the study beforehand.

1. Patients with tumor embolus in portal vein
2. Patients with an ongoing hepatic intra-arterial chemotherapy such as implantable reservoir system
3. Patients with hepatocellular cancer of more than 3 cm in diameter or more than four hepatocellular cancers
4. Patients with residual or chronic portal vein thrombosis
5. Patients with advanced liver disease (Child-Pugh score 11 or more)
6. Patients with bleeding tendency
7. Patients who had an anticoagulation therapy (intravenous or subcutaneous dose) or hemostasis with an enzymatic hemostatic agent in the period between 7 days before contrast enhanced CT of pre-dose and the day acquired written informed consent
8. Patients who had an anticoagulation therapy (oral dose) in the period between 7 days before contrast enhanced CT of pre-dose and the day acquired written informed consent
9. Patients with a history of shock or hypersensitivity to NPB-06

10. Patients with inappropriate to contrast agents

    • A history of allergy of iodine or X-ray contrast agent
    • Complication of serious thyroid disease
    • Reduced renal function
11. Pregnant or lactating women, women of childbearing potential, or women who plan to become pregnant during the study
12. Patients who have received NPB-06
13. Patients who have received other investigational drugs within four months before consent or who are participating in other clinical studies
14. Patients otherwise ineligible for participation in the study in the investigator's or subinvestigator's opinion

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NPB-06; 1,500 unit, 5 days continuous-infusion	Drug: NPB-06; 5 days continuous-infusion
Placebo Comparator: Placebo; 0 unit, 5 days continuous-infusion	Drug: Placebo; 5 days continuous-infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of patients obtained complete recanalization or partial recanalization of portal vein thrombosis	Contrast enhanced CT assessed by an independent radiologist	an expected average of 2 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
The proportion of patients obtained complete recanalization of portal vein thrombosis	an expected average of 2 weeks
Reduction rate of portal vein thrombosis	Up to 3 weeks
Improvement of Child-Pugh score	Up to 5 weeks
Changes in laboratory values (congealing fibrinogenolysis system)	Up to 5 weeks
Adverse events and adverse drug reactions observed between administration and 21 ± 3 days after administration	Up to 5 weeks

Collaborators and Investigators

• Sponsor: Nihon Pharmaceutical Co., Ltd

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: September 20, 2014
• First Submitted That Met QC Criteria: September 24, 2014
• First Posted (Estimate): September 26, 2014

Study Record Updates

• Last Update Posted (Estimate): September 9, 2016
• Last Update Submitted That Met QC Criteria: September 7, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis
• Other Study ID Numbers: NPB-06-04/C-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No