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

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ClinicalTrials.gov Identifier: NCT03236506
Recruitment Status : Recruiting
First Posted : August 2, 2017
Last Update Posted : April 5, 2019
Sponsor:
Information provided by (Responsible Party):
John Dillon, University of Dundee

Brief 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.


Condition or disease Intervention/treatment Phase
Hepatitis C Drug: Zepatier Pill Behavioral: Psychological intervention Drug: Sofosbuvir Pill Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 135 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised, un-blinded trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Direct obserVed therApy vs fortNightly CollEction Study for HCV Treatment - ADVANCE HCV Study
Actual Study Start Date : January 19, 2018
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : March 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Daily observed therapy
Patients with active hepatitis C infection genotype 1 will receive 12 weeks treatment with Zepatier at one tablet per day. Patients with active hepatitis C infection genotype 3 will receive 8 weeks treatment with Zepatier pill plus Sofosbuvir pill at one of each tablets per day. These tablets will be given to patients on a daily, observed basis by either the nurse or a community pharmacist.
Drug: Zepatier Pill
Drugs will be given to participants to treat hepatitis C infection

Drug: Sofosbuvir Pill
Drugs will be given along with Zepatier to participants to treat genotype 3hepatitis C infection

Active Comparator: Fortnightly pick-up
Patients with active hepatitis C infection genotype 1 will receive 12 weeks treatment with Zepatier at one tablet per day. Patients with active hepatitis C infection genotype 3 will receive 8 weeks treatment with Zepatier pill plus Sofosbuvir pill at one of each tablets per day. These tablets will be given to patients on a fortnightly basis by the nurse.
Drug: Zepatier Pill
Drugs will be given to participants to treat hepatitis C infection

Drug: Sofosbuvir Pill
Drugs will be given along with Zepatier to participants to treat genotype 3hepatitis C infection

Active Comparator: Fortnightly pick-up +psych intervention
Patients with active hepatitis C infection genotype 1 will receive 12 weeks treatment with Zepatier at one tablet per day. Patients with active hepatitis C infection genotype 3 will receive 8 weeks treatment with Zepatier pill plus Sofosbuvir pill at one of each tablets per day. These tablets will be given to patients on a fortnightly basis by the nurse. In addition, this group will receive a one-off interview with the researcher to complete a psychological intervention designed to improve adherence to the medication regimen.
Drug: Zepatier Pill
Drugs will be given to participants to treat hepatitis C infection

Behavioral: Psychological intervention
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.

Drug: Sofosbuvir Pill
Drugs will be given along with Zepatier to participants to treat genotype 3hepatitis C infection




Primary Outcome Measures :
  1. Efficacy of directly acting antiviral therapies in HCV positive, active PWIDs, administered via directly observed therapy, fortnightly pick-up or fortnightly pick-up with a psychological adherence intervention. [ Time Frame: 24 weeks for gen1 HCV, 20 weeks for gen3 HCV infection ]
    Sustained viral response rates at 12 weeks post treatment of participants in the DOT, fortnightly pick-up or fortnightly pick-up with a psychological adherence intervention group


Secondary Outcome Measures :
  1. Demonstration that the achieved SVR rates in HCV PWID participants with DAA treatment are similar to randomised controlled trial results and therefore a cost-effective treatment [ Time Frame: 12 weeks for gen1 HCV, 8 weeks for gen3 HCV infection ]
    Adherence of daily directly observed therapy group from daily logs Adherence measured by counting tablets returned after each 2 week treatment period (fortnightly pickup groups) Adherence of participants infected with genotype 3 and treated with Sovaldi measured using medication event monitoring system (MEMS®) cap.

  2. Assessment of reinfection rates in active PWIDs treated with oral DAA regimes [ Time Frame: Annually up to 5 years ]
    Hepatitis C viral load from PCR

  3. Assessment of resistance profiles in those who do not achieve SVR [ Time Frame: Bloods collected at baseline, end of treatment and 12 weeks post end of treatment ]
    Profiles of the HCV viral resistance proteins, NS5a and NS3

  4. Assessment of the types of illicit drugs taken by trial participants and identification of any interaction with the directly acting therapies. [ Time Frame: At three timepoints; time zero (before treatment), time 2-8 weeks (during treatment) time 12 weeks (at the end of treatment) ]
    Drug misuse history and urine toxicology



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03236506


Contacts
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Contact: Sarah K Inglis, PhD 01382 383219 s.k.inglis@dundee.ac.uk
Contact: John Dillon, MD 01382 632176 j.dillon@nhs.net

Locations
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United Kingdom
University of Dundee Not yet recruiting
Dundee, Tayside, United Kingdom, DD1 9SY
NHS Tayside Recruiting
Dundee, United Kingdom, DD1 9SY
Contact: John Dillon, MD         
Sponsors and Collaborators
University of Dundee

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: John Dillon, Professor John Dillon, University of Dundee
ClinicalTrials.gov Identifier: NCT03236506     History of Changes
Other Study ID Numbers: 2016GA03
2017-001039-38 ( EudraCT Number )
First Posted: August 2, 2017    Key Record Dates
Last Update Posted: April 5, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by John Dillon, University of Dundee:
Illicit drug
Injecting drug
Additional relevant MeSH terms:
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Hepatitis C
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Flaviviridae Infections
RNA Virus Infections
Sofosbuvir
Elbasvir-grazoprevir drug combination
Antiviral Agents
Anti-Infective Agents