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Trial registered on ANZCTR


Registration number
ACTRN12611000513910
Ethics application status
Approved
Date submitted
17/05/2011
Date registered
18/05/2011
Date last updated
16/10/2015
Type of registration
Prospectively registered

Titles & IDs
Public title
Treatment of recently acquired hepatitis C infection study
Scientific title
The effectiveness of Response-guided therapy strategies in recent hepatitis C infection
Secondary ID [1] 262185 0
5RO1 DA 15999
Universal Trial Number (UTN)
Trial acronym
ATAHC II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 265867 0
Condition category
Condition code
Infection 266023 266023 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group 1: Untreated subjects - subjects who are not eligible or chose not to receive anti-hepatitis C treatment will be followed for up to 2 years.
Group 2: Treated subjects - subjects who are eligible for anti-hepatitis C treatment and chose to receive treatment will receive response-guided treatment. The duration of treatment will depend on the subject's virological response, ranging from 8 to 48 weeks. The type of treatment received will depend on the estimated duration of hepatitis C infection and HIV disease status. Subjects will receive pegylated interferon alfa-2a with or without ribavirin.
Early acute sub-group: Subjects who have been infected within the last 12 weeks of screening will be eligible to participate in the early acute sub-study and have 4 extra visits for collection of research blood samples between screening and baseline visits.
The mode of administration of pegylated interferon alfa-2a is subcutaneous injection 180mcg weekly. The mode of administration of ribavirin is oral tablet, 800mg to 1200mg daily depending on the genotype of the subject (and the body weight of the subject if genotype 1).
Intervention code [1] 264593 0
Treatment: Drugs
Comparator / control treatment
The rate of sustained virological response (SVR) of study subjects using response-guided therapy in this study will be compared to the SVR rates in historical controls in the ATAHC I (Australian Trial in Acute Hepatitis C) with ANZCTR registration number: ACTRN 12605000435684
Control group
Historical

Outcomes
Primary outcome [1] 266769 0
To evaluate the effectiveness of response-guided therapy strategies in recent hepatitis C (HCV) infection.
Timepoint [1] 266769 0
The proportion of treated subjects with SVR24 defined as undetectable HCV RNA 24 weeks post therapy.
Secondary outcome [1] 276356 0
To examine the rate and predictors of spontaneous clearance of recent HCV infection
Timepoint [1] 276356 0
Untreated subjects achieving HCV clearance as defined by two consecutive undetectable HCV RNA (below level of detection <=15IU/ml by Roche TaqMan assay) over an interval of >=4 weeks
Secondary outcome [2] 276357 0
To characterise the natural history, and outcomes following treatment, of recent HCV infection by HIV status
Timepoint [2] 276357 0
Proportion of treated subjects with HCV RNA <=15IU/ml at week 2, 4, 6, 8 and 12 of therapy; proportion of treated subjects with HCV RNA <=15IU/ml at therapy completion, at week 12 after therapy completion (SVR12) and at last study follow-up; proportion of treated subjects with SVR24 by treatment duration
Secondary outcome [3] 276358 0
To study host genetic factors associated with hepatitis C outcomes
Timepoint [3] 276358 0
Screening
Secondary outcome [4] 276359 0
To examine the incidence and predictors of reinfection following spontaneous and treatment induced clearance of recent HCV.
The incidence of HCV reinfection during and following HCV treatment will be determined among all participants with treatment-induced HCV RNA suppression and >= 4 weeks on-treatment follow-up. Virologic suppression will be defined by one positive HCV RNA tests followed by >= one negative qualitative HCV RNA test(s) <=15 IU/ml.
Confirmed HCV reinfection will be defined as recurrent viraemia with a different viral sequence as initial infection as confirmed by viral sequencing. Possible HCV reinfection will be defined as recurrent viraemia in which either the initial or reinfection timepoint could not be sequenced.
Factors associated with HCV reinfection will be assessed through comparison of baseline demographic (age, gender), clinical (HIV status) and behavioural (IDU vs
MSM acquired, IDU frequency, drug type) factors as well as longitudinal clinical (peak ALT) and behavioural (IDU frequency, needle sharing) factors among cases and non-cases.
Timepoint [4] 276359 0
Screening and longitudinal time-points (the screening blood sample will be sequenced, and the blood samples collected at subsequent time-points will be sequenced if the subject becomes HCV RNA positive again after achieving viral suppression).
Secondary outcome [5] 276360 0
To define the incidence and prevalence of HCV superinfection in individuals with recent HCV infection infection at baseline and during the first 12 weeks of therapy
Timepoint [5] 276360 0
All subjects' screening HCV RNA samples will be tested for mixed HCV infection; those subjects who are still HCV RNA detectable at week 4 and week 12 will have HCV RNA samples re-sequenced
Secondary outcome [6] 276361 0
To determine the prevalence and complexity of HCV protease and polymerase inhibitor mutations in recent HCV infection
Timepoint [6] 276361 0
Screening
Secondary outcome [7] 276362 0
To allow the collection and storage of PBMC and plasma samples with the aim of establishing a specimen bank for future immunovirological studies of acute HCV
Timepoint [7] 276362 0
EDTA buffy coats: at screening; EDTA plasma for treated subjects: at screening, baseline, while on treatment, at end of treatment, at SVR12, SVR24, follow-up one and follow-up two; EDTA plasma for untreated subjects: at screening, baseline, week 4, 8, 12, 24, 48, 72 and 96; ACD PBMC treated subjects: at screening, baseline, week 4, end of treatment, and SVR24; ACD PBMC untreated subjects: screening, baseline, week 4, 24 and 48

Eligibility
Key inclusion criteria
Male and female subjects >= 16 years of age

To have recently acquired HCV infection as defined below:

A)
i) First anti-HCV antibody or HCV RNA positive within the previous 6 months
and
ii) Documented anti-HCV antibody negative within the 24 months prior to anti-HCV antibody positive result

OR

B)
i) First anti-HCV antibody or HCV RNA positive within the previous 6 months
and
ii) acute clinical hepatitis (jaundice or ALT> 10 X ULN) within the previous 12 months prior to first positive HCV antibody or HCV RNA, with no other cause of acute hepatitis identifiable
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Individuals considered by the study investigators to be unlikely to participate in intensive follow-up and/or unwilling to provide extra blood samples, and standard exclusion criteria for pegylated interferon alfa-2a and ribavirin.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Two study groups, treated and untreated group, and a historical control group to compare the SVR rates in the treated group in this study
Phase
Phase 4
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/06/2011
Actual
22/09/2011
Date of last participant enrolment
Anticipated
Actual
28/07/2014
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
82
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 488 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [2] 489 0
The Alfred - Prahran
Recruitment hospital [3] 490 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 491 0
Nepean Hospital - Kingswood
Recruitment hospital [5] 492 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [6] 493 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [7] 495 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 6236 0
5000 - Adelaide
Recruitment postcode(s) [2] 4011 0
NSW 1340
Recruitment postcode(s) [3] 4009 0
NSW 2010
Recruitment postcode(s) [4] 4010 0
NSW 2050
Recruitment postcode(s) [5] 4012 0
NSW 2751
Recruitment postcode(s) [6] 4013 0
VIC 3004
Recruitment postcode(s) [7] 4014 0
VIC 3050
Recruitment postcode(s) [8] 4015 0
VIC 3065

Funding & Sponsors
Funding source category [1] 267090 0
Government body
Name [1] 267090 0
National Institute on Drug Abuse, National Institutes of Health
Country [1] 267090 0
United States of America
Primary sponsor type
University
Name
The University of New South Wales (acting through the Kirby Institute, formerly the National Centre in HIV Epideiology and Clinical Research))
Address
The University of New South Wales, Sydney, NSW 2052
Country
Australia
Secondary sponsor category [1] 264180 0
University
Name [1] 264180 0
The Kirby Institute (formerly the National Centre in HIV Epidemiology and Clinical Research)
Address [1] 264180 0
CFI Building, crn Boundary and West Streets, Darlinghurst, NSW 2010
Country [1] 264180 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 267067 0
St. Vincent's Hospital Human Research Ethics Committee
Ethics committee address [1] 267067 0
Level 6, deLacy Building, St. Vincent's Hospital, Victoria Street, Darlinghurst, NSW 2010
Ethics committee country [1] 267067 0
Australia
Date submitted for ethics approval [1] 267067 0
Approval date [1] 267067 0
17/03/2011
Ethics approval number [1] 267067 0
HREC/10/SVH/137
Ethics committee name [2] 267068 0
The Alfred Human Research Ethics Committee, VIC
Ethics committee address [2] 267068 0
Commercial Road, Melbourne, VIC 3004
Ethics committee country [2] 267068 0
Australia
Date submitted for ethics approval [2] 267068 0
15/06/2011
Approval date [2] 267068 0
Ethics approval number [2] 267068 0
Ethics committee name [3] 267069 0
Royal Adelaide Research Ethics Committee, SA
Ethics committee address [3] 267069 0
North Terrace, Adelaide, SA 5000
Ethics committee country [3] 267069 0
Australia
Date submitted for ethics approval [3] 267069 0
27/04/2011
Approval date [3] 267069 0
Ethics approval number [3] 267069 0
Ethics committee name [4] 267070 0
Metro South Health Service District Human Research Ethics Committee, QLD
Ethics committee address [4] 267070 0
Ipwich Road, Woolloongabba, QLD 4102
Ethics committee country [4] 267070 0
Australia
Date submitted for ethics approval [4] 267070 0
14/04/2011
Approval date [4] 267070 0
Ethics approval number [4] 267070 0

Summary
Brief summary
ATAHC II is a prospective longitudinal study of natural history and treatment outcomes following response-guided treatment of recent HCV infection.
The main aim of the study is to identify the optimal therapeutic strategy for patients with recently acquired HCV infection. Eligible subjects will be offered HCV treatment with pegylated interferon alfa-2a with or without ribavirin, depending on their HIV status and their duration of infection. The duration of treatment will be guided by the subject’s virological response to treatment and will range from 8 weeks to 48 weeks.
Subjects who are not eligible for HCV treatment or chose not to receive HCV treatment will be followed at regular intervals for 2 years
Trial website
www.kirby.unsw.edu.au
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 32616 0
Prof Gregory Dore
Address 32616 0
The Kirby Institute (formerly the National Centre in HIV Epidemiology and Clinical Research), CFI Building, corner Boundary and West Streets, Darlinghurst NSW 2010, Australia
Country 32616 0
Australia
Phone 32616 0
+61 2 9385 0900
Fax 32616 0
+61 2 9385 9214
Email 32616 0
gdore@kirby.unsw.edu.au
Contact person for public queries
Name 15863 0
Ms Barbara Yeung
Address 15863 0
The Kirby Institute (formerly the National Centre in HIV Epidemiology and Clinical Research), CFI Building, corner Boundary and West Streets, Darlinghurst NSW 2010
Country 15863 0
Australia
Phone 15863 0
+61 2 93850879
Fax 15863 0
+61 2 93859214
Email 15863 0
byeung@kirby.unsw.edu.au
Contact person for scientific queries
Name 6791 0
Dr Gail Matthews
Address 6791 0
The Kirby Institute (formerly the National Centre in HIV Epidemiology and Clinical Research), CFI Building, corner Boundary and West Streets, Darlinghurst NSW 2010, Australia
Country 6791 0
Australia
Phone 6791 0
+61 2 93850900
Fax 6791 0
+61 2 93859214
Email 6791 0
gmatthews@kirby.unsw.edu.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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