Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12605000488606
Ethics application status
Approved
Date submitted
14/09/2005
Date registered
23/09/2005
Date last updated
14/11/2019
Date data sharing statement initially provided
14/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Chariot Study
Scientific title
A Phase IV, Randomised, Multi-centre, Efficacy and Safety Study Examining the Effect of Induction Dosing with the combination of peginterferon Alfa-2a and Ribavirin in Patients with Chronic Hepatitis C Infected with Hepatitis C Genotype 1.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Hepatitis C genotype 1 610 0
Condition category
Condition code
Inflammatory and Immune System 682 682 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pegylated interferon alfa 2a and ribavirin for 48 weeks.
Intervention code [1] 601 0
Treatment: Drugs
Comparator / control treatment
Control group
Active

Outcomes
Primary outcome [1] 832 0
To evaluate the effect of peginterferon alfa-2a (Pegasys) plus ribavirin combination therapy induction dosing versus no induction dosing on the clearance of HCV viremia in patients with chronic hepatitis C (CHC) infected with HCV genotype 1.
Timepoint [1] 832 0
24 weeks after completion of a 48 week treatment period (sustained virological response).
Secondary outcome [1] 1641 0
To compare the effect of Pegasys plus ribavirin induction dosing versus no induction dosing on serum ALT.
Timepoint [1] 1641 0
24 weeks after completion of a 48 week treatment period (sustained biochemical response).
Secondary outcome [2] 1642 0
To compare the effect of Pegasys plus ribavirin induction dosing versus no induction dosing on the combined endpoint of clearance of HCV viraemia and normalization of serum ALT.
Timepoint [2] 1642 0
24 weeks after completion of a 48 week treatment period (sustained virological and biochemical response).
Secondary outcome [3] 1643 0
To evaluate the effect of induction dosing versus no induction dosing on the reduction of HCV viremia.
Timepoint [3] 1643 0
After 4, 8, 12, 24 weeks of treatment with Pegasys plus ribavirin.
Secondary outcome [4] 1644 0
To compare the safety of Pegasys plus ribavirin induction dosing versus no induction dosing.
Timepoint [4] 1644 0
Secondary outcome [5] 1645 0
To evaluate the predictors of sustained virological response to treatment with Pegasys plus ribavirin induction dosing versus no induction dosing.
Timepoint [5] 1645 0

Eligibility
Key inclusion criteria
Serologic evidence of chronic hepatitis C infection (repeatedly anti-HCV positive and/or HCV-RNA positive)- Infection with HCV; meets section 100 criteria for treatment with Pegasys RBV- Compensated liver disease, Child Pugh score <7- Quantifiable Serum HCV-RNA - Patients who are naive to any hepatitis C therapy (i.e. have not been previously treated with an interferon or with IFN plus ribavirin) - Chronic liver disease consistent with chronic hepatitis C infection on a biopsy obtained within the past 18 months as judged by a local pathologist. (Exception: hemophiliacs in whom biopsy is medically contra-indicated do not require biopsy. The section 100 criteria states that in patients with coagulation disorders considered severe enough to prevent liver biopsy, evidence of abnormal serum ALT levels is required.) - Patients with transition to cirrhosis or cirrhosis (Metavir (or equivalent index) stage 3 or 4) must have an abdominal ultrasound, CT scan, or MRI scan without evidence of hepatocellular carcinoma and a serum AFP <100 ng/mL within 2 months of randomisation- Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drugAll fertile males and females receiving ribavirin must be using two forms of effective contraception during treatment and during the 6 months after treatment end.
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Standard exclusion criteria for pegylated interferon and ribavirin.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Centrally randomised
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
SAS, permuted blocks, stratified by viral load
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
18/08/2004
Actual
2/02/2009
Date of last participant enrolment
Anticipated
Actual
2/02/2009
Date of last data collection
Anticipated
Actual
2/02/2009
Sample size
Target
816
Accrual to date
Final
896
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 757 0
Commercial sector/Industry
Name [1] 757 0
Roche Products Pty Ltd
Country [1] 757 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Roche Products Pty Ltd
Address
Level 8/30-34 Hickson Rd, Millers Point NSW 2000
Country
Switzerland
Secondary sponsor category [1] 625 0
University
Name [1] 625 0
National Centre in HIV Epidemiology and Clinical Research - UNSW
Address [1] 625 0
UNSW Sydney, Sydney, NSW 2052
Country [1] 625 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1976 0
Albion Street Clinic
Ethics committee address [1] 1976 0
Ethics committee country [1] 1976 0
Australia
Date submitted for ethics approval [1] 1976 0
Approval date [1] 1976 0
22/06/2004
Ethics approval number [1] 1976 0
Ethics committee name [2] 1977 0
Austin Hospital
Ethics committee address [2] 1977 0
Ethics committee country [2] 1977 0
Australia
Date submitted for ethics approval [2] 1977 0
Approval date [2] 1977 0
17/06/2004
Ethics approval number [2] 1977 0
Ethics committee name [3] 1978 0
Bankstown Hospital
Ethics committee address [3] 1978 0
Ethics committee country [3] 1978 0
Australia
Date submitted for ethics approval [3] 1978 0
Approval date [3] 1978 0
15/09/2004
Ethics approval number [3] 1978 0
Ethics committee name [4] 1979 0
Box Hill Hospital
Ethics committee address [4] 1979 0
Ethics committee country [4] 1979 0
Australia
Date submitted for ethics approval [4] 1979 0
Approval date [4] 1979 0
24/09/2004
Ethics approval number [4] 1979 0
Ethics committee name [5] 1980 0
Concord Repatriation Hospital
Ethics committee address [5] 1980 0
Ethics committee country [5] 1980 0
Australia
Date submitted for ethics approval [5] 1980 0
Approval date [5] 1980 0
24/06/2004
Ethics approval number [5] 1980 0
Ethics committee name [6] 1981 0
Flinders Medical Centre
Ethics committee address [6] 1981 0
Ethics committee country [6] 1981 0
Australia
Date submitted for ethics approval [6] 1981 0
Approval date [6] 1981 0
04/04/2005
Ethics approval number [6] 1981 0
Ethics committee name [7] 1982 0
Frankston Hospital
Ethics committee address [7] 1982 0
Ethics committee country [7] 1982 0
Australia
Date submitted for ethics approval [7] 1982 0
Approval date [7] 1982 0
15/07/2005
Ethics approval number [7] 1982 0
Ethics committee name [8] 1983 0
Fremantle Hospital
Ethics committee address [8] 1983 0
Ethics committee country [8] 1983 0
Australia
Date submitted for ethics approval [8] 1983 0
Approval date [8] 1983 0
13/07/2004
Ethics approval number [8] 1983 0
Ethics committee name [9] 1984 0
Geelong Hospital
Ethics committee address [9] 1984 0
Ethics committee country [9] 1984 0
Australia
Date submitted for ethics approval [9] 1984 0
Approval date [9] 1984 0
19/11/2004
Ethics approval number [9] 1984 0
Ethics committee name [10] 1985 0
John Hunter Hospital
Ethics committee address [10] 1985 0
Ethics committee country [10] 1985 0
Australia
Date submitted for ethics approval [10] 1985 0
Approval date [10] 1985 0
08/07/2004
Ethics approval number [10] 1985 0
Ethics committee name [11] 1986 0
Liverpool Hospital
Ethics committee address [11] 1986 0
Ethics committee country [11] 1986 0
Australia
Date submitted for ethics approval [11] 1986 0
Approval date [11] 1986 0
15/09/2004
Ethics approval number [11] 1986 0
Ethics committee name [12] 1987 0
Liverpool Sexual Health Clinic
Ethics committee address [12] 1987 0
Ethics committee country [12] 1987 0
Australia
Date submitted for ethics approval [12] 1987 0
Approval date [12] 1987 0
15/09/2004
Ethics approval number [12] 1987 0
Ethics committee name [13] 1988 0
Monash Medical Centre
Ethics committee address [13] 1988 0
Ethics committee country [13] 1988 0
Australia
Date submitted for ethics approval [13] 1988 0
Approval date [13] 1988 0
20/04/2005
Ethics approval number [13] 1988 0
Ethics committee name [14] 1989 0
Nambour Hospital
Ethics committee address [14] 1989 0
Ethics committee country [14] 1989 0
Australia
Date submitted for ethics approval [14] 1989 0
Approval date [14] 1989 0
08/10/2005
Ethics approval number [14] 1989 0
Ethics committee name [15] 1990 0
Nepean Hospital
Ethics committee address [15] 1990 0
Ethics committee country [15] 1990 0
Australia
Date submitted for ethics approval [15] 1990 0
Approval date [15] 1990 0
12/08/2004
Ethics approval number [15] 1990 0
Ethics committee name [16] 1991 0
Princess Alexandra Hospital
Ethics committee address [16] 1991 0
Ethics committee country [16] 1991 0
Australia
Date submitted for ethics approval [16] 1991 0
Approval date [16] 1991 0
28/10/2004
Ethics approval number [16] 1991 0
Ethics committee name [17] 1992 0
Royal Adelaide Hospital
Ethics committee address [17] 1992 0
Ethics committee country [17] 1992 0
Australia
Date submitted for ethics approval [17] 1992 0
Approval date [17] 1992 0
30/07/2004
Ethics approval number [17] 1992 0
Ethics committee name [18] 1993 0
Royal Brisbane Hospital
Ethics committee address [18] 1993 0
Ethics committee country [18] 1993 0
Australia
Date submitted for ethics approval [18] 1993 0
Approval date [18] 1993 0
21/07/2004
Ethics approval number [18] 1993 0
Ethics committee name [19] 1994 0
Did not participate
Ethics committee address [19] 1994 0
Ethics committee country [19] 1994 0
Australia
Date submitted for ethics approval [19] 1994 0
Approval date [19] 1994 0
01/01/2004
Ethics approval number [19] 1994 0
Ethics committee name [20] 1995 0
Royal Melbourne Hospital
Ethics committee address [20] 1995 0
Ethics committee country [20] 1995 0
Australia
Date submitted for ethics approval [20] 1995 0
Approval date [20] 1995 0
13/05/2005
Ethics approval number [20] 1995 0
Ethics committee name [21] 1996 0
Royal Perth Hospital
Ethics committee address [21] 1996 0
Ethics committee country [21] 1996 0
Australia
Date submitted for ethics approval [21] 1996 0
Approval date [21] 1996 0
22/07/2004
Ethics approval number [21] 1996 0
Ethics committee name [22] 1997 0
Royal Prince Alfred Hospital
Ethics committee address [22] 1997 0
Ethics committee country [22] 1997 0
Australia
Date submitted for ethics approval [22] 1997 0
Approval date [22] 1997 0
27/05/2004
Ethics approval number [22] 1997 0
Ethics committee name [23] 1998 0
Sir Charles Gairdner Hospital
Ethics committee address [23] 1998 0
Ethics committee country [23] 1998 0
Australia
Date submitted for ethics approval [23] 1998 0
Approval date [23] 1998 0
15/11/2004
Ethics approval number [23] 1998 0
Ethics committee name [24] 1999 0
St George Hospital
Ethics committee address [24] 1999 0
Ethics committee country [24] 1999 0
Australia
Date submitted for ethics approval [24] 1999 0
Approval date [24] 1999 0
29/06/2004
Ethics approval number [24] 1999 0
Ethics committee name [25] 2000 0
St Vincent's Hospital NSW
Ethics committee address [25] 2000 0
Ethics committee country [25] 2000 0
Australia
Date submitted for ethics approval [25] 2000 0
Approval date [25] 2000 0
17/05/2004
Ethics approval number [25] 2000 0
Ethics committee name [26] 2001 0
St Vincent's Hospital Victoria
Ethics committee address [26] 2001 0
Ethics committee country [26] 2001 0
Australia
Date submitted for ethics approval [26] 2001 0
Approval date [26] 2001 0
25/01/2005
Ethics approval number [26] 2001 0
Ethics committee name [27] 2002 0
The Alfred Hospital
Ethics committee address [27] 2002 0
Ethics committee country [27] 2002 0
Australia
Date submitted for ethics approval [27] 2002 0
Approval date [27] 2002 0
Ethics approval number [27] 2002 0
Ethics committee name [28] 2003 0
Townsville Hospital
Ethics committee address [28] 2003 0
Ethics committee country [28] 2003 0
Australia
Date submitted for ethics approval [28] 2003 0
Approval date [28] 2003 0
25/11/2004
Ethics approval number [28] 2003 0
Ethics committee name [29] 2004 0
Western Hospital
Ethics committee address [29] 2004 0
Ethics committee country [29] 2004 0
Australia
Date submitted for ethics approval [29] 2004 0
Approval date [29] 2004 0
13/05/2005
Ethics approval number [29] 2004 0

Summary
Brief summary
The purpose of the study is to compare the effectiveness of two treatment regimens in clearing the Hepatitis C Virus in patients infected with Hepatitis C genotype 1.

The study aims to determine whether a higher dose of pegylated interferon given in combination with ribavirin for the first 12 weeks of therapy results in a higher rate of viral clearance and whether it is safe and tolerable.
Trial website
Trial related presentations / publications
Impact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: a randomized controlled trial. Roberts SK, Weltman MD, Crawford DH, McCaughan GW, Sievert W, Cheng WS, Rawlinson W, Desmond PV, Marks PS, Yoshihara M, Rizkalla B, Depamphilis JK, Dore GJ; Chariot Study Group. Hepatology. 2009 Oct;50(4):1045-55. doi: 10.1002/hep.23130. PMID: 19676125

ITPA genotype protects against anemia during peginterferon and ribavirin therapy but does not influence virological response. Holmes JA, Roberts SK, Ali RJ, Dore GJ, Sievert W, McCaughan GW, Crawford DH, Cheng WS, Weltman MD, Bonanzinga S, Visvanathan K, Sundararajan V, Desmond PV, Bowden DS, Matthews GV, Thompson AJ; CHARIOT Study Group. Hepatology. 2014 Jun;59(6):2152-60. doi: 10.1002/hep.27022. Epub 2014 Apr 25. PMID: 24449403

Distribution of interferon lambda-3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: Analysis from the PREDICT and CHARIOT studies. Roberts SK, Mitchell J, Leung R, Booth D, Bollipo S, Ostapowicz G, Sloss A, McCaughan GW, Dore GJ, Thompson A, Crawford DH, Sievert W, Weltman M, Cheng W, George J; Australian Liver Association Clinical Research Network. J Gastroenterol Hepatol. 2014 Jan;29(1):179-84. doi: 10.1111/jgh.12424. PMID: 24219707

Early on-treatment viral load and baseline METAVIR score: improved prediction of sustained virological response in HCV genotype 1 patients. Crawford DH, Dore GJ, Sievert W, Cheng WS, Weltman M, McCaughan G, Rawlinson W, Marks PS, Yoshihara M, Rizkalla B, Roberts SK; CHARIOT Study Group. Antivir Ther. 2012;17(5):849-54. doi: 10.3851/IMP2104. Epub 2012 Apr 18. PMID: 22513456

Virological response is associated with decline in hemoglobin concentration during pegylated interferon and ribavirin therapy in hepatitis C virus genotype 1. Sievert W, Dore GJ, McCaughan GW, Yoshihara M, Crawford DH, Cheng W, Weltman M, Rawlinson W, Rizkalla B, Depamphilis JK, Roberts SK; CHARIOT Study Group. Hepatology. 2011 Apr;53(4):1109-17. doi: 10.1002/hep.24180. PMID: 21480317

Low virological response and high relapse rates in hepatitis C genotype 1 patients with advanced fibrosis despite adequate therapeutic dosing. Cheng WS, Roberts SK, McCaughan G, Sievert W, Weltman M, Crawford D, Rawlinson W, Marks PS, Thommes J, Rizkalla B, Yoshihara M, Dore GJ; CHARIOT Study Group. J Hepatol. 2010 Oct;53(4):616-23. doi: 10.1016/j.jhep.2010.04.024. Epub 2010 Jun 16. PMID: 20619475
Public notes

Contacts
Principal investigator
Name 35902 0
Address 35902 0
Country 35902 0
Phone 35902 0
Fax 35902 0
Email 35902 0
Contact person for public queries
Name 9790 0
Elizabeth Knight
Address 9790 0
National Centre in HIV Epidemiology and Clinical Research (NCHECR)
Level 2
376 Victoria Street
Darlinghurst NSW 2010
Country 9790 0
Australia
Phone 9790 0
+61 2 93850900
Fax 9790 0
Email 9790 0
[email protected]
Contact person for scientific queries
Name 718 0
Dr Stuart Roberts
Address 718 0
Department of Gastroenterology
The Alfred Hospital
Commercial Road
Melbourne VIC 3004
Country 718 0
Australia
Phone 718 0
+61 3 92762223
Fax 718 0
Email 718 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AIImpact of high-dose peginterferon alfa-2A on virological response rates in patients with hepatitis C genotype 1: A randomized controlled trial2009https://doi.org/10.1002/hep.23130
Dimensions AIVirological response is associated with decline in hemoglobin concentration during pegylated interferon and ribavirin therapy in hepatitis C virus genotype 12011https://doi.org/10.1002/hep.24180
Dimensions AIInterleukin-28B rs12979860 C allele2014https://doi.org/10.1111/jgh.12544
N.B. These documents automatically identified may not have been verified by the study sponsor.