A Direct obserVed therApy vs fortNightly CollEction Study for HCV Treatment - ADVANCE HCV Study

• Status: Completed
• Trial end date: 2020-12-21
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Dundee
• Treatments: Elbasvir-grazoprevir drug combination; Sofosbuvir

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)