Reaching mEthadone Users Attending Community pHarmacies With HCV
Reaching mEthadone Users Attending Community pHarmacies With HCV
Hepatitis C Virus (HCV) is a blood-borne virus that damages the liver and is a major public
 health threat globally. Most individuals infected with HCV are unaware of it and show no
 symptoms until presenting with incurable, fatal end-stage disease. In Scotland and Australia
 approximately 0.7% of the general population has chronic HCV with 0.4% in Wales, and they are
 at risk of developing cirrhosis and hepatocellular carcinoma. The clinical challenge is to
 identify those infected and bring them into treatment before the disease advances.

 The greatest risk factor for acquiring HCV in many countries is through injecting drug use.
 On the road to recovery from drug use, many will receive long-term opiate substitution
 therapy (OST), commonly with methadone or buprenorphine. Internationally, OST is routinely
 dispensed by a community pharmacist. HCV testing can be offered by GPs, drugs workers, drug
 agencies, social workers, community pharmacies and needle exchange sites. Once patients are
 diagnosed, they are referred to a hospital-based service to receive anti-HCV treatment. In
 this pathway, less than 10% of the OST population is tested per year, and cumulative rates of
 testing are less than 50% of those on OST.

 Highly effective Directly Acting Antiviral (DAA) treatment combinations are now available and
 achieve HCV cure rates in excess of 95%, with once or twice daily tablets for 8-24 weeks.

 The REACH HCV study will compare efficacy of an education-only HCV referral and treatment
 pathway against a nurse-led point-of-care device testing and treatment pathway among OST
 patients in community pharmacies in Scotland, Wales and Australia. Eligible participants will
 be treated using DAAs.
The REACH HCV study is an international, cluster-randomised non-clinical trial with two arms.
 The unit of randomisation is the community pharmacy, so all participants in a given pharmacy
 are allocated to one of two pathways for HCV testing and treatment. There are three
 participating hubs located in: Scotland, Wales and Australia respectively.

 The sample size is 140 participants, equally split between the three participating hubs, and
 the trial population is patients receiving opiate substitution therapy (OST) in community
 pharmacies.

 Arm 1 (REACH arm): The community pharmacist will take the opportunity to explain the risks of
 contracting HCV from current or historical intravenous drug use. The OST patients will then
 meet with an outreach hepatology nurse specialist who will consent the patients and perform a
 diagnostic point-of-care (PoC) HCV test along with venepuncture for safety laboratory blood
 tests and confirmatory HCV RNA. The outreach nurse will return for a subsequent visit to
 prescribe (in the UK; in Australia prescribing is undertaken by qualified medic) and deliver
 HCV medication for those patients who test positive, which will be dispensed to participants
 alongside their OST schedule by their community pharmacist. The outreach nurse will return
 after approximately 14 days to confirm negative results, dispense medication for new patients
 with positive results (PCR positive but below limit of detection of POC test) and confirm
 follow up appointments where required. The RNA and PoC test will also be administered for
 sustained viral response at 12 weeks post treatment (SVR12).

 Arm 2 (Education-only arm): The community pharmacist will discuss the risks of contracting
 HCV through current or historical intravenous drug use. The community pharmacist will then
 advise participants on the nearest centre for HCV testing and treatment, as is standard of
 care for the countries included in this study. If they are referred from a REACH pharmacy,
 they will present a reply slip and/or the Patient Information Sheet to the nurse who will
 then consent the participant, perform HCV and safety blood tests, and complete the study
 paperwork. The participant's medication will be delivered to, and dispensed from, their
 community pharmacy alongside their OST. Participants will return to the local BBV clinic for
 an SVR12 test after completing treatment.

 All eligible HCV-infected participants will receive treatment with 100mg glecaprevir/40mg
 pibrentasvir (Maviret) a pan-genotypic Direct Acting Antiviral (DAA) for between 8-16 weeks,
 depending on blood test results. The study is planned to run for a total of two years, with
 one year clinical phase and one year follow-up phase.
Inclusion Criteria:

 -  Over 18 years of age.

 -  Previous or current injecting drug user.

 -  Stable OST dose for greater than 12 weeks prior to study enrolment.

 -  Glecaprevir/pibrentasvir treatment naïve.

 -  Able to voluntarily sign and date an informed consent form prior to initiation of any
 screening or study specific procedures.

 -  Able to understand and adhere to study visit schedule and all other protocol
 requirements.

 Exclusion Criteria:

 -  Female who is pregnant, planning to become pregnant or breastfeeding or
 unwilling/unable to take appropriate birth control.

 -  Known current HIV infection.

 -  Known current HBV infection. Serological: patients with a positive HBsAg or isolated
 positive anti-HBC will be excluded from the study and followed up in secondary care.

 -  Previous treatment with glecaprevir/pibrentasvir.

 -  Currently taking any concomitant medication that has a warning of'do not
 co-administer' with glecaprevir and/or pibrentasvir as defined by the Liverpool Hep
 drug interactions website and product SmPC.

 -  Clinically significant abnormalities that make candidate unsuitable for this study in
 the opinion of the investigator including but not limited to:

 -  Uncontrolled cardiac, respiratory, gastrointestinal, hematologic, neurologic,
 psychiatric or other medical disease or disorder, which is unrelated to existing HCV
 infection.

 -  History of either current or previous decompensated liver disease or symptoms/signs of
 decompensation e.g. ascites noted on physical exam, use of beta-blockers for portal
 hypertension, hepatic encephalopathy or oesophageal variceal bleeding.

 -  Candidate is deemed unsuitable to receive study drugs by the study investigator, for
 any reason according to clinical judgement.

 -  Unable or unwilling to provide informed consent.

 -  History of severe, life-threatening or other significant sensitivity to any excipients
 of the study drugs.

 -  Drug-drug Interaction which may have safety concerns with any concomitant medication
 the patient is receiving including non-prescribed and/or recreational drugs.