A Direct obserVed therApy vs fortNightly CollEction Study for HCV Treatment - ADVANCE HCV Study
Condition: Hepatitis C
MeSH terms: Hepatitis C
Intervention: Elbasvir/Grazoprevir 50 MG-100 MG Oral Tablet; Psychological intervention; Sofosbuvir 400 MG
Intervention description: Drugs will be given to participants to treat hepatitis C infection; Participants randomised to fortnightly pick-up with psychological intervention will have an interview with the study nurse designed to aid their compliance with the drug regimen. During the intervention participants will be guided by their trial nurse in the completion of a personalised booklet, "Hepatitis C and Me". The booklet uses the principles of node-link mapping to structure the intervention.; Drugs will be given along with Zepatier to participants to treat genotype 3hepatitis C infection
Intervention MeSH terms: Sofosbuvir; Grazoprevir; Elbasvir-grazoprevir drug combination
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomised, un-blinded trial
Masking: None (Open Label)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Illicit drug; Injecting drug

Summary:

      Hepatitis C is a blood borne virus that can seriously damage the liver. An estimated 50,000
      Scots have been infected with Hepatitis C virus (HCV). The main driver for spread of HCV
      infection is intravenous drug use. As HCV is highly infectious by the blood borne route
      through needle sharing, it can infect the person who injects drugs (PWID) early in their
      habit.

      Around two thirds of people who are infected are unaware of it, and often show no symptoms
      over a long period of time. While there is presently no vaccination for Hepatitis C, improved
      treatments with shorter duration are now available. This raises the possibility of using
      therapy as prevention, turning the epidemic off at source, by targeting active PWID who are
      the main source of new infections. Modelling work illustrates the startling possibility and
      impact of treating drug users to reduce the prevalence of HCV.

      The focus of this trial will be to ascertain whether oral treatment regimens are effective in
      the treatment as prevention scenario in an active PWID population where illicit drug taking
      and poor adherence may reduce treatment efficacy. The investigators will trial 3 different
      methods of delivering treatment and will trial an unlicensed combined treatment against HCV
      genotype 3 infection of shortened duration since current regimens for this genotype are
      limited.

      The investigators will recruit 135 participants and randomise them to one of three arms:
      daily, directly observed therapy; fortnightly dispensing of drugs; fortnightly dispensing of
      drugs with a psychological adherence intervention. Randomisation will be stratified according
      to HCV genotype. Participants will be treated for 12 or 8 weeks depending on genotype and
      followed up 12 weeks post treatment for the measurement of sustained viral response (SVR).
      The primary outcome measure will be SVR at 12 weeks post treatment (SVR12), as this measure
      of cure is the determinant of sufficient compliance and efficacy within the 3 treatment arms.
      Analysis will be by modified intention to treat of all participants who receive one dose of
      therapy, to show non-inferiority fortnightly dispensing is easier to deliver than daily
      dispensing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or Female. (Age limit 18-70)

          -  HCV PCR confirmed active infection, genotype 1 or 3.

          -  If female, must have negative urine test results for pregnancy during initial
             screening period (for trial inclusion) and be advised of limited safety data in
             pregnancy.

          -  Current illicit drug use established through participant history.

          -  Able to provide informed consent, agreeing to trial and clinical monitoring criteria

        Exclusion Criteria:

          -  Aggressive or violent behaviour.

          -  Platelet count < 75000000000 /ml

          -  Alanine transaminase > 350 Units/l

          -  Inability to provide informed consent.

          -  Clinical history or abnormal valves for albumin< 30 g/l, Bilirubin >35 umol/l or
             prothrombin time >1.5 consistent with decompensated liver failure Childs-Pugh B or C

          -  Clinical history of primary hepatocellular carcinoma

          -  Pregnancy or breast feeding.

          -  Participation in a drug trial within the previous 30 days

          -  Hepatitis B surface antigen positive

          -  HIV infection.

          -  Hypersensitivity to elbasvir and grazoprevir

          -  Hypersensitivity to sofosbuvir (genotype 3 infected-participants ony)

          -  Currently being treated with an inhibitor of organic anion transporting polypeptide
             1B, e.g. rifampicin, atazanavir, daruavir, lopinavir, saquinavir, tipranavir,
             cobicistat or ciclosporin.

          -  Currently being treated with inducers of cytochrome P450 3A or P-glycoprotein, such as
             efavirenz, phenytoin, carbamazepine, bosentan, etravirine, modafinil or St John's Wort
             (Hypericum perforatum)

          -  Currently being treated with amiodarone (Participants infected with genotype 3 HCV
             only)