Clinical trial NCT03935906: Reaching mEthadone Users Attending Community pHarmacies With HCV
Official title: Reaching mEthadone Users Attending Community pHarmacies With HCV
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatitis C
Keywords: Point of Care
Direct Acting Antivirals
Community Pharmacy
Opiate Substitution Therapy
Lead sponsor: University of Dundee
Sponsor class: OTHER
Collaborators: name: Public Health Wales
name: Burnet Institute
First posted: 2019-05-02
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: SVR12
timeFrame: 12 weeks after participants finish their hepatitis C treatment regimen
Secondary outcomes:
measure: Determine whether the REACH pathway compared with the education only pathway leads to more people on opiate substitution therapy who are confirmed HCV RNA positive being treated and cured.
timeFrame: 12 weeks after participants finish their hepatitis C treatment regimen
measure: Cost-effectiveness analysis of the REACH pathway versus the education-only pathway, from the perspective of the NHS (UK) and Medicare (Australia).
timeFrame: 2 years
measure: Determine whether the REACH pathway compared with the education-only pathway leads to more people on opiate substitution therapy being tested for HCV.
timeFrame: 2 years
measure: Compare adherence and persistence to HCV therapy in the Reach pathway to the education-only pathway.
timeFrame: 2 years
measure: Assess the impact of baseline blood tests on treatment decisions.
timeFrame: 2 years
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: The Burnet Institute
city: Dundee
country: United Kingdom
facility: NHS Tayside
state: Scotland
city: Cardiff
country: United Kingdom
facility: Public Health Wales
state: Wales
Study officials:
affiliation: Public Health Wales
name: Brendan Healy, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Macfarlane Burnet Institute for Medical Research and Public Health
name: Joseph Doyle, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Dundee
name: John F Dillon, PhD
role: STUDY_DIRECTOR
References:
citation: Byrne CJ, Radley A, Inglis SK, Beer L, Palmer N, Duc Pham M, Allardice K, Wang H, Robinson E, Hermansson M, Semizarov D, Healy B, Doyle JS, Dillon JF. Reaching people receiving opioid agonist therapy at community pharmacies with hepatitis C virus: an international randomised controlled trial. Aliment Pharmacol Ther. 2022 Jun;55(12):1512-1523. doi: 10.1111/apt.16953. Epub 2022 May 10.
citation: Byrne C, Radley A, Inglis SK, Beer LJZ, Palmer N, Pham MD, Healy B, Doyle JS, Donnan P, Dillon JF. Reaching mEthadone users Attending Community pHarmacies with HCV: an international cluster randomised controlled trial protocol (REACH HCV). BMJ Open. 2020 Aug 30;10(8):e036501. doi: 10.1136/bmjopen-2019-036501.