Double Filtration Plasmapheresis for Hepatitis C Virus (HCV) Genotype 1 Patients With High Viral Load

Summary

Hepatitis C virus (HCV) infection, a leading cause of cirrhosis, hepatocellular carcinoma (HCC) and liver transplantation, affects approximately 170 million individuals worldwide. The prevention of HCV transmission and early intervention of HCV infection are urgently needed to reduce or halt the liver-related morbidity and mortality. Double filtration plasmapheresis (DFPP) has been with widespread use in clinical practice for several indications with plasma filters optimized for the respective elimination targets with excellent safety. By way of the plasma separator, the blood is separated into plasma and cell components. Separated plasma is then led into the plasma component separator where the pores of the plasma component separator further fractionate the plasma into large and small molecular components. The large molecular components, including pathogenic substances, is removed and discarded and the small molecular components, including proteins such as albumin and gamma-globulin, are returned to the patient and mixed with the cell components. After the initiation of pegylated interferon plus ribavirin (Peg-IFN+RBV) therapy, the rapid first phase relates to a significant reduction in virus production and the degradation of free virus particles, which is followed by a second much slower one reflecting the elimination and clearance of infected cells. In HCV patients, high baseline viral load at the initiation of therapy is considered to be a negative predictor for systemic vascular resistance (SVR) for HCV genotype 1 patients. Reduction of baseline viral load by means of therapeutic double filtration plasmapheresis (DFPP) may represent a plausible adjunct for improved antiviral therapy to reduce the virus load with the initiation of treatment in synergy with Peg-IFN and RBV combination therapy. Recently, several clinical studies in evaluating the therapeutic efficacy and safety of DFPP in conjunction with IFN-based therapy were conducted for treatment-naïve genotype 1 high viral load CHC patients, and CHC patients who underwent liver transplantation. These studies showed that patients with DFPP treatment had more favorable HCV early viral kinetics to those without DFPP treatment. Furthermore, all these studies showed excellent safety after DFPP treatment. Therefore, the investigators aimed to conduct a large-scaled randomized controlled trial to evaluate the overall response of DFPP for HCV genotype 1 patients with high viral load.

Conditions

• Hepatitis C

Interventions

DRUG

DFPP + Peg-IFN + RBV

Double filtration plasmapheresis: day 1,2,4,8,9 from the onset of treatment (4 hours for each session) Peginterferon alfa-2a: week 1-48, weekly subcutaneous 180 ug Ribavirin: week 1-48, daily oral 1,000-1,200 mg (body weight \< 75 kg, 1,000 mg/day; body weight loss \>= 75 kg, 1,200 mg/day)

DRUG

Peg-IFN + RBV

Peginterferon alfa-2a: week 1-48, weekly subcutaneous 180 ug Ribavirin: week 1-48, daily oral 1,000-1,200 mg (body weight \< 75 kg, 1,000 mg/day; body weight loss \>= 75 kg, 1,200 mg/day)

Sponsors & Collaborators

• National Science and Technology Council, Taiwan

  collaborator OTHER_GOV

• Department of Health, Executive Yuan, R.O.C. (Taiwan)

  collaborator OTHER_GOV

• National Taiwan University Hospital

  lead OTHER

Principal Investigators

• Chen-Hua Liu, MD · National Taiwan University Hospital

• Jia-Horng Kao, MD, PhD · National Taiwan University Hospital

• Shih-Jer Hsu, MD · National Taiwan University Hospital, Yun-Lin Branch

• Cheng-Chao Liang, MD, BS · Far Eastern Memorial Hospital

• Hung-Bin Tsai, MD · Buddhist Tzu Chi General Hospital

• Peir-Haur Hung, MD · Chiayi Christian Hospital

• Chih-Lin Lin, MD, BS · Taipei Municipal Hospital, Ren-Ai Branch

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-09-30

Primary Completion

2012-12-31

Completion

2012-12-31

Countries

• Taiwan

Study Locations