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Trial registered on ANZCTR


Registration number
ACTRN12608000400369
Ethics application status
Approved
Date submitted
30/06/2008
Date registered
8/08/2008
Date last updated
29/01/2010
Type of registration
Retrospectively registered

Titles & IDs
Public title
A single-arm, open-label, pilot study evaluating the efficacy and safety of directly observed peginterferon alfa-2a with ribavirin in conjunction with a peer counsellor in patients actively using injecting drugs who have chronic hepatitis C and attend a drug and alcohol centre.
Scientific title
A single-arm, open-label, pilot study evaluating the efficacy and safety of directly observed peginterferon alfa-2a with ribavirin in conjunction with a peer counsellor in patients actively using injecting drugs who have chronic hepatitis C and attend a drug and alcohol centre.
Universal Trial Number (UTN)
Trial acronym
DOT-PEER-IDU-HCV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Impact of standard pharmacotherapy treatment of chronic Hepatitis C virus (HCV) infection on: (i) quality of life, (ii) mental health status, (iii) injecting drug behaviours, and (iv) opioid pharmacotherapy use in active injecting drug users (IDUs). 3336 0
Side effects related to chronic Hepatitis C virus (HCV) infection and treatment in active injecting drug users (IDUs). 3337 0
Factors affecting compliance of active injecting drug users (IDUs) for standard pharmacotherapy treatment of chronic Hepatitis C virus (HCV) infection. 3338 0
Chronic hepatitis C virus (HCV) infection. 3342 0
Condition category
Condition code
Public Health 3490 3490 0 0
Other public health
Mental Health 3491 3491 0 0
Addiction
Infection 3495 3495 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Administration of pegylated interferon alfa-2a plus ribavirin combination therapy (Roche PEGASYS (Registered) RBV (Registered) Combination Therapy) to active injecting drug users with chronic Hepatitis C infection (HCV) for a period of 24 to 48 weeks who will be subjected to the following interventions:

1. Directly observed administration of pegylated interferon alfa-2a (to ensure therapy compliance),

2. Ribavirin pill counting and adherence questioning (to monitor therapy compliance), and

3. Peer counsellor assistance (to encourage therapy compliance).

Participant visits to the investigator site will be comprised of: one screening visit for eligibility and safety assessments in the 8 weeks prior to treatment initiation, 24 to 48 therapy/study visits for treatment and safety assessments and three follow-up visits at 4, 12 and 24 weeks post-treatment completion for safety assessments.

The overall period of intervention will be 56 or 80 weeks for the 24 or 48 week treatment regimens respectively.

Participants infected with HCV genotype 2 or 3 who don't have hepatic cirrhosis or bridging fibrosis will be assigned to the 24 week treatment regimen of peginterferon alfa-2a 180 micrograms/week and ribavirin 800 mg/day (unless contraindicated). Participants infected with HCV genotype 2 or 3 who have hepatic cirrhosis or bridging fibrosis or those infected with HCV genotypes other than 2 or 3 will be assigned to the 48 week treatment regimen of peginterferon alfa-2a 180 micrograms/week and ribavirin 1000 or 1200 mg/day (unless contraindicated).

PEGASYS (Registered) comes in pre-filled syringes as a sterile, ready-to-use solution. One PEGASYS (Registered) dose of 180 micrograms will be administered by subcutaneous injection into the stomach or thigh area once weekly under direct observation during a study/therapy visit at the investigator site. The duration of the directly observed therapy (DOT) will be equivalent to the time required to prepare and administer the injection.

COPEGUS (or RBV; Registered) is available as 200 mg tablets that are dispensed in bottles of 112, 140 or 168 tablets (equivalent to 4 weeks of treatment). Tablets will be self-administered daily in the home as morning and evening doses taken orally with food ( 1 hour prior to or 2 hours after a meal). Participants assigned to the 24 week treatment regimen will take 2 tablets morning and evening (2 x 400 mg = 800 mg/day). Participants assigned to the 48 week treatment regimen who weigh <75 kg will take 2 and 3 tablets in the morning and evening respectively (400 mg + 600 mg = 1000 mg/day), whereas those who weigh >=75 kg will take 3 tablets morning and evening (2 x 600 mg = 1200 mg/day).

Therapy compliance for ribavirin will be evaluated via adherence questioning and pill counting every 4 weeks.

The essential role of the peer counsellor will be to facilitate HCV therapy compliance by providing participant advocacy and assistance to participants in the management of physical and psychological issues associated with HCV pharmacotherapy and opioid addiction and pharmacotherapy. The peer counsellor will accompany participants to all study visits including screening, baseline, therapy and follow-up visits where the duration of these visits will depend upon the study procedures being performed (30 minutes - 2 hours). In addition to these scheduled visits, participants will have 24 hours/day, 7 days/week access to peer counsellor support where the method, nature, frequency and duration of contact will be determined by the participant in accordance with their needs. The details of these unscheduled interactions will be recorded in a log maintained by the peer counsellor.
Intervention code [1] 3069 0
Other interventions
Intervention code [2] 3070 0
Behaviour
Intervention code [3] 3074 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 4396 0
Therapy compliance as measured by the proportion of participants who comply with the treatment regimen of directly observed therapy by attending at least 80% of treatment visits.
Timepoint [1] 4396 0
At the end of year 3 when all participant follow-up visits are complete.
Primary outcome [2] 4400 0
Therapy compliance as measured by the proportion of participants who complete therapy by taking 80% of HCV treatment (both pegylated interferon alpha 2a and ribavirin).
Timepoint [2] 4400 0
At the end of year 3 when all participant follow-up visits are complete.
Secondary outcome [1] 7421 0
Impact of therapy on the participant's injecting behaviour and use of pharmacotherapy. The outcomes will be measured by the following means:

(a) performing urine drug screens at the screening (pre-treatment), baseline (treatment initiation), 2 weeks post-baseline, and follow-up (4, 12 and 24 weeks post-treatment) visits, and at visits every 4 weeks during the treatment period, and

b) administration of the Opiate Treatment Index (OTI) questionnaire at the screening and baseline visits and subsequently every 12 weeks throughout the treatment and follow-up periods.
Timepoint [1] 7421 0
At the end of year 3 when all participant follow-up visits are complete.
Secondary outcome [2] 7422 0
Impact of therapy on the participant's psychological status. The outcomes will be measured by the administration of the Mini International Neurophychiatric Interview (M.I.N.I; English Version 5.0.0) and Beck Depression Inventory, (BDI-II; 2nd edition) questionnaires at the screening (pre-treatment), baseline (treatment initiation), 2 weeks post-baseline, and follow-up (4, 12 and 24 weeks post-treatment) visits, and at visits every 4 weeks during the treatment period. Questionnaire results will be reviewed by a psychiatrist and significant changes in psychological status identified will trigger further psychiatric review of the participant.
Timepoint [2] 7422 0
At the end of year 3 when all participant follow-up visits are complete.
Secondary outcome [3] 7423 0
Impact of therapy on participant's quality of life. The outcomes will be measured by the administration of the SF-12 Health Survey (Australian/New Zealand Standard Version 1.0) at the screening and baseline visits and subsequently every 12 weeks throughout the treatment and follow-up periods.
Timepoint [3] 7423 0
At the end of year 3 when all participant follow-up visits are complete.
Secondary outcome [4] 7424 0
The acceptability and utility of the peer counsellor amongst study participants. The outcomes will be measured by direct questioning of participants at every visit throughout the study, by evaluation of visit attendance records and by evaluation of the peer counsellor and participant contact log.
Timepoint [4] 7424 0
At the end of year 3 when all participant follow-up visits are complete.
Secondary outcome [5] 7425 0
The acceptability of Directly Observed Therapy (DOT) amongst study participants. The outcomes will be measured by direct questioning of participants at every visit throughout the study and by evaluation of visit attendance records.
Timepoint [5] 7425 0
At the end of the 24 or 48 week treatment period.
Secondary outcome [6] 7426 0
Proportion of participants with mild, moderate and severe side effects related to HCV infection. Adverse events will be recorded at every visit throughout the study.
Timepoint [6] 7426 0
At the end of year 3 when all participant follow-up visits are complete.
Secondary outcome [7] 7430 0
Proportion of participants who achieve a Sustained Viral Response (SVR) following treatment. SVR will be evaluated by testing of participant serum for the presence of virus at screening, end of therapy and end of follow-up time-points, and by measurement of serum viral loads at screening and 12 weeks post treatment initiation.
Timepoint [7] 7430 0
At the end of year 3 when all participant follow-up visits are complete.

Eligibility
Key inclusion criteria
Informed consent

Age = 18 years

Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test and positive HCV PCR (Polymerase Chain Reaction) for > 6 months

Detectable serum HCV-RNA (ribonucleic acid) at screening

Compensated liver disease (Child-Pugh Grade A clinical classification)

Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug

All fertile males and females and their partners must be using effective contraception during treatment and during the 6 months after treatment end

Have had an episode of injecting drug use within 4 weeks of screening

Drinking 2 standard drinks or less of alcohol per day ( binge drinking will be allowed as long as it does not exceed 6 standard drinks for males and 4 standard drinks for females less than every 2 weeks)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Frequency of injecting drug use of daily or greater

Females who are pregnant, breastfeeding or planning a pregnancy

Inability or unwillingness to provide informed consent or abide by the requirements of the study protocol

Patients unwilling to use an acceptable method of birth control (defined as surgical sterility, intrauterine device, oral contraception, diaphragm or condom in association with a spermicide)

Patients previously treated with interferon or ribavirin

Evidence of excessive substance abuse as judged by the investigator

Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) <=6 months prior to the first dose of study drug

Any investigational drug <=4 weeks or 5 half lives, whichever is longer, prior to the first dose of study drug

Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, anti-HIV Ab

History or other evidence of a medical condition associated with chronic liver disease other than HCV (eg. hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease)

History or other evidence of bleeding from oesophageal varices or other conditions consistent with decompensated liver disease as evidenced by Child’s Pugh score B or C

Neutrophil count <1500 cells/mm3 or platelet count <75,000 cells/mm3 at screening

Serum creatinine level >1.5 times the upper limit of normal at screening

History of severe psychiatric disease (defined as schizophrenia, active bipolar disorder, severe anorexia, serious or multiple episodes of self harm, currently high or moderate suicide risk, current major depressive episode or current psychosis)

History of a severe seizure disorder or current anticonvulsant use

History of immunologically-mediated disease, chronic pulmonary disease associated with functional limitation, severe cardiac disease, major organ transplantation or other evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study

History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease

Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration)

Hgb <12 g/dL in women or <13 g/dL in men at screening

Any patient with an increased baseline risk for anaemia (e.g. thalassemia, spherocytosis, history of gastrointestinal (GI) bleeding, etc) or for whom anaemia would be medically problematic

Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in haemoglobin by up to 4 g/dL (as may be seen with ribavirin therapy) would not be well-tolerated

Other significant comorbidity or contraindication to therapy of study participation as determined by investigator

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
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/08/2008
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 936 0
2751
Recruitment postcode(s) [2] 937 0
3011
Recruitment postcode(s) [3] 938 0
3050

Funding & Sponsors
Funding source category [1] 3538 0
Commercial sector/Industry
Name [1] 3538 0
Roche Products Pty Ltd
Country [1] 3538 0
Australia
Primary sponsor type
Individual
Name
Dr Joe Sasadeusz
Address
Victorian Infectious Diseases Service,
Level 9-North, Main Building,
The Royal Melbourne Hospital, City Campus,
Grattan Street, Parkville, Victoria, 3050
Country
Australia
Secondary sponsor category [1] 3176 0
Hospital
Name [1] 3176 0
Melbourne Health
Address [1] 3176 0
The Royal Melbourne Hospital, City Campus,
Grattan Street, Parkville, Victoria, 3050
Country [1] 3176 0
Australia
Other collaborator category [1] 319 0
Hospital
Name [1] 319 0
Western Hospital, DASWest
Address [1] 319 0
16 Eleanor Street,
Footscray, Victoria, 3011
Country [1] 319 0
Australia
Other collaborator category [2] 321 0
Hospital
Name [2] 321 0
Sydney West Area Health Service, Nepean Campus
Address [2] 321 0
PO Box 63, Penrith, NSW, 2751
Country [2] 321 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5578 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 5578 0
Research Directorate,
Level 6-East, Main Building,
The Royal Melbourne Hospital, City Campus,
Grattan Street, Parkville, Victoria, 3050
Ethics committee country [1] 5578 0
Australia
Date submitted for ethics approval [1] 5578 0
16/07/2008
Approval date [1] 5578 0
12/11/2008
Ethics approval number [1] 5578 0

Summary
Brief summary
Hepatitis C virus (HCV) is the most common blood borne virus affecting injecting drug users (IDUs). 90% of new cases of Hepatitis C in Australia are attributable to injecting drug use. Hepatitis C treatment is effective in clearing the virus in between 50% and 80% of cases and is cost effective when considering the averted treatment costs of chronic viral hepatitis. Despite this there are a number of barriers to the effective treatment of IDUs, and as a consequence only 2-3% of IDUs are estimated to have received HCV treatment.This study proposes to treat active IDUs for hepatitis C infection using directly observed (DOT) pegylated interferon and ribavirin therapy in accordance with current Pharmaceutical Benefits Scheme legislation. Participants will be regularly assessed for psychological status and drug use utilising a variety of registered questionnaires. Participants will be monitored and guided throughout the study with the support of a peer counsellor. This person will provide participants with the guardianship, advocacy, interaction and education required to effectively manage personal and study-related issues (physical and psychological), to encourage treatment compliance and to reinforce safe injecting practices.The primary outcomes are: (i) achievement of sustained virological response, which is defined as having no detectable hepatitis C virus 6 months after the completion of treatment, (ii) achievement of treatment compliance, which will be determined from the proportion of patients attending =80% of DOT visits and the proportion of patients taking =80% of the HCV treatment, and (iii) determination of the value of a peer counsellor in HCV treatment of active IDUs when the physical and mental health, substance use and treatment compliance of participants is actively monitored. This study is designed to increase the opportunity for effective and supported hepatitis C treatment in active injecting drug users. The study aims to show that active IDUs can achieve successful outcomes from hepatitis C treatment and to determine those variables which are important in achieving this, including the value of a peer counsellor to the treatment team.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28712 0
Address 28712 0
Country 28712 0
Phone 28712 0
Fax 28712 0
Email 28712 0
Contact person for public queries
Name 11869 0
Dr Tseng Lau
Address 11869 0
Victorian Infectious Diseases Service,
Level 9-North, Main Building,
The Royal Melbourne Hospital, City Campus,
Grattan Street, Parkville, Victoria, 3050
Country 11869 0
Australia
Phone 11869 0
+61 3 93428274
Fax 11869 0
+61 3 93427277
Email 11869 0
tseng.lau@mh.org.au
Contact person for scientific queries
Name 2797 0
Dr Joe Sasadeusz
Address 2797 0
Victorian Infectious Diseases Service,
Level 9-North, Main Building,
The Royal Melbourne Hospital, City Campus,
Grattan Street, Parkville, Victoria, 3050
Country 2797 0
Australia
Phone 2797 0
+61 3 93428616
Fax 2797 0
+61 3 93427277
Email 2797 0
Joe.Sasadeusz@mh.org.au

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