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

NCT00977054 | Terminated Phase 4

• 1 other identifier: 200904053D
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 6

Brief 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

Keywords

Hepatitis C; Peginterferon alfa-2a; Ribavirin; Plasmapheresis; Genotype 1

Outcome Measures

Primary Outcomes (1)

• Sustained virologic response (SVR)

  18 months

Secondary Outcomes (2)

• Rapid virologic response (RVR)

  1 month

• Treatment-related withdrawal rate

  12 months

Study Arms (2)

DFPP and Peg-IFN + RBV

EXPERIMENTAL

Double filtration plasmapheresis (Day 1, Day 2, Day 4, Day 8, and Day 9 from the onset of treatment; overall 5 session, each session for 4 hours) and weekly subcutaneous peginterferon alfa-2a 180 ug (week 1 to week 48) and daily oral ribavirin 1,000-1,200 mg (week 1 to week 48; body weight \< 75 kg, 1,000 mg/day and body weight \>= 75 kg, 1,200 mg/day)

Drug: DFPP + Peg-IFN + RBV

Peg-IFN + RBV

ACTIVE COMPARATOR

Weekly subcutaneous peginterferon alfa-2a 180 ug (week 1 to week 48) and daily oral ribavirin 1,000-1,200 mg (week 1-48; body weight \< 75 kg, 1,000 mg/day and body weight \>=75 kg, 1,200 mg/day)

Drug: Peg-IFN + RBV

Interventions

DFPP + Peg-IFN + RBV DRUG

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)

Also known as: DFPP: Plasmaflo + Cascadeflo EC-50W (Asahi), Peg-IFN alfa-2a: Pegasys (Hoffman La-Roche), RBV: Copegus (Hoffman La-Roche)

DFPP and Peg-IFN + RBV

Peg-IFN + RBV DRUG

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)

Also known as: Peg-IFN alfa-2a: Pegasys (Hoffman La-Roche), RBV: Copegus (Hoffman La-Roche)

Peg-IFN + RBV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Treatment naïve
• Age 18 and older
• Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive \> 6 months
• Detectable serum quantitative HCV-RNA (Cobas Taqman v2.0, Roche Diagnostics) with HCV RNA \> 800,000 IU/mL
• HCV genotype 1 (Inno-LiPA, Innogenetics)
• A liver biopsy consistent with the diagnosis of chronic hepatitis C

You may not qualify if:

• Anemia (hemoglobin \< 13 gram per deciliter for men and \< 12 gram per deciliter for women)
• Neutropenia (neutrophil count \<1,500 per cubic milliliter)
• Thrombocytopenia (platelet \<90,000 per cubic milliliter)
• Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
• Chronic alcohol abuse (daily consumption \> 20 gram per day)
• Decompensated liver disease (Child-Pugh class B or C)
• Serum creatinine level more than 1.5 times the upper limit of normal
• Autoimmune liver disease
• Neoplastic disease
• An organ transplant
• Immunosuppressive therapy
• Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
• Evidence of drug abuse
• Unwilling to have contraception

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• National Science and Technology Council, Taiwan: collaborator
• Department of Health, Executive Yuan, R.O.C. (Taiwan): collaborator

Study Sites (6)

Buddhist Tzu Chi General Hospital

Chiayi City, Taiwan

Location

Chiayi Christian Hospital

Chiayi City, Taiwan

Location

National Taiwan University Hospital, Yun-Lin Branch

Douliu, Taiwan

Location

Far Eastern Memorial Hospital

Taipei, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Taipei Municipal Hospital

Taipei, Taiwan

Location

MeSH Terms

Conditions

Hepatitis C

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Chen-Hua Liu, MD

  National Taiwan University Hospital

  STUDY CHAIR

• Jia-Horng Kao, MD, PhD

  National Taiwan University Hospital

  STUDY DIRECTOR

• Shih-Jer Hsu, MD

  National Taiwan University Hospital, Yun-Lin Branch

  PRINCIPAL INVESTIGATOR

• Cheng-Chao Liang, MD, BS

  Far Eastern Memorial Hospital

  PRINCIPAL INVESTIGATOR

• Hung-Bin Tsai, MD

  Buddhist Tzu Chi General Hospital

  PRINCIPAL INVESTIGATOR

• Peir-Haur Hung, MD

  Chiayi Christian Hospital

  PRINCIPAL INVESTIGATOR

• Chih-Lin Lin, MD, BS

  Taipei Municipal Hospital, Ren-Ai Branch

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2009
• First Posted: September 15, 2009
• Study Start: September 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: December 20, 2012

Record last verified: 2012-12

Locations

TW (6)