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.
Dr Joe Sasadeusz
50 participants
Aug 1, 2008
Interventional
Conditions
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.
Eligibility
Inclusion Criteria9
- 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)
Exclusion Criteria22
- 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
Interventions
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.
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12608000400369