Ignite Creation Date:
2024-05-05 @ 9:50 PM
Last Modification Date:
2024-10-26 @ 10:10 AM
Study NCT ID:
NCT00977054
Status:
TERMINATED
Last Update Posted:
2012-12-20
First Post:
2009-09-13
Brief Title:
Double Filtration Plasmapheresis for Hepatitis C Virus HCV Genotype 1 Patients With High Viral Load
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Double Filtration Plasmapheresis DFPP in Combination With Pegylated Interferon Alfa-2a and Ribavirin for Patients With Chronic Hepatitis C With Genotype 1 and High Viral Load a Randomized Controlled Trial
Status:
TERMINATED
Status Verified Date:
2012-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Novel HCV DAA approved by FDA
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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-IFNRBV 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
Detailed Description:
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 Currently combination therapy with peginterferon Peg-IFN and ribavirin RBV has become the standard of care for chronic hepatitis C CHC patients with an overall sustained virologic response SVR rate of 54-63 Treatment with weekly Peg-IFN and weight-based RBV for 48 weeks resulted in a significantly higher SVR rate than that for 24 weeks in patients with HCV genotype 1 infection While HCV genotype 1 patients who had both rapid virologic response RVR and low pretreatment viral load could receive short duration of therapy without compromising the treatment responses those who had either high baseline viral load or failed to achieve RVR should receive at least 48 weeks of treatment RVR is considered the most important factor for SVR Furthermore several studies have repeated shown that high baseline viral load 400000800000 IUmL was closely associated with failure to achieve RVR in these patients Therefore efforts to improve the RVR rate is important to facilitate the overall treatment responses
Double filtration plasmapheresis DFPP a well established method of therapeutic apheresis has been with widespread use in clinical practice for several indications with plasma filters optimized for the respective elimination targets 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
DFPP has been used in the treatment of many diseases such as neurological diseases collagen diseases hematological diseases skin diseases and renal diseases and its efficacy and safety have been well established It is noteworthy to mention that DFPP has been indicated to treat CHC in Japan since April 2008 In Germany the safety of DFPP in LDL-apheresis was analyzed within a retrospective multicenter investigation including data from 1702 ambulatory DFPP-LDL-apheresis treatments of 52 patients REMUKAST Study Ninety-eight percent of the treatments bear no serious adverse events while only 2 of slight hypotensive episodes were observed In a recent investigation efficacy and safety of DFPP was compared with the HELP Heparin-induced Extracorporeal LDL-Cholesterol Precipitation system in a cross-over design No serious adverse events occurred in this study including 44 treatments
During chronic infection the level of serum HCV RNA is in a steady state with only minor fluctuations in untreated patients A dynamic equilibrium involving hepatocytes and plasma components exists between new viral production and viral destruction during chronic HCV infection After the initiation of Peg-IFN plus RBV therapy the viral decline can be divided into two major phases Over the first 24 - 48 h the initial dose of PEG-IFNRBV leads to a first decline of HCV RNA which ranges from 05-20 log levels This 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
As described above a high baseline viral load HCV-RNA 800000 IUmL at the initiation of therapy is considered to be a negative predictor for SVR for HCV genotype 1 patients Reduction of baseline viral load by means of therapeutic 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 Therefore the rationale for the effect of DFPP is that the reduced amount of virus during the initiation phase supports the therapeutic efficacy of Peg-IFN and RBV combination therapy by preventing liver reinfection by circulating HCV
Recently several small-scaled clinical studies in evaluating the therapeutic efficacy and safety of DFPP in conjunction with IFN-based therapy were conducted for treatment-naïve genotyp1 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 The large-scaled non-randomized clinical study totally evaluating 104 CHC patients showed that the addition of DFPP had a higher SVR rate to those without DFPP treatment in HCV genotype 1 patients with baseline viral load 100000 IUmL 708 versus 500 probably due to eliminating a substantial part of viral particles from the dynamic equilibrium of the liver and plasma compartments Furthermore all these studies showed excellent safety after DFPP treatment However these studies were limited by the small case numbers and non-randomized assignment making the role of DFPP in improving the efficacy of difficult-to-treat HCV patients still debated 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
Double filtration plasmapheresis DFPP a well established method of therapeutic apheresis has been with widespread use in clinical practice for several indications with plasma filters optimized for the respective elimination targets 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
DFPP has been used in the treatment of many diseases such as neurological diseases collagen diseases hematological diseases skin diseases and renal diseases and its efficacy and safety have been well established It is noteworthy to mention that DFPP has been indicated to treat CHC in Japan since April 2008 In Germany the safety of DFPP in LDL-apheresis was analyzed within a retrospective multicenter investigation including data from 1702 ambulatory DFPP-LDL-apheresis treatments of 52 patients REMUKAST Study Ninety-eight percent of the treatments bear no serious adverse events while only 2 of slight hypotensive episodes were observed In a recent investigation efficacy and safety of DFPP was compared with the HELP Heparin-induced Extracorporeal LDL-Cholesterol Precipitation system in a cross-over design No serious adverse events occurred in this study including 44 treatments
During chronic infection the level of serum HCV RNA is in a steady state with only minor fluctuations in untreated patients A dynamic equilibrium involving hepatocytes and plasma components exists between new viral production and viral destruction during chronic HCV infection After the initiation of Peg-IFN plus RBV therapy the viral decline can be divided into two major phases Over the first 24 - 48 h the initial dose of PEG-IFNRBV leads to a first decline of HCV RNA which ranges from 05-20 log levels This 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
As described above a high baseline viral load HCV-RNA 800000 IUmL at the initiation of therapy is considered to be a negative predictor for SVR for HCV genotype 1 patients Reduction of baseline viral load by means of therapeutic 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 Therefore the rationale for the effect of DFPP is that the reduced amount of virus during the initiation phase supports the therapeutic efficacy of Peg-IFN and RBV combination therapy by preventing liver reinfection by circulating HCV
Recently several small-scaled clinical studies in evaluating the therapeutic efficacy and safety of DFPP in conjunction with IFN-based therapy were conducted for treatment-naïve genotyp1 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 The large-scaled non-randomized clinical study totally evaluating 104 CHC patients showed that the addition of DFPP had a higher SVR rate to those without DFPP treatment in HCV genotype 1 patients with baseline viral load 100000 IUmL 708 versus 500 probably due to eliminating a substantial part of viral particles from the dynamic equilibrium of the liver and plasma compartments Furthermore all these studies showed excellent safety after DFPP treatment However these studies were limited by the small case numbers and non-randomized assignment making the role of DFPP in improving the efficacy of difficult-to-treat HCV patients still debated 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None