Intensive Models of HCV Care for Injection Drug Users

NCT01857245 | Completed Results DMC

• 2 other identifiers: 1R01DA034086-01, 2011-5551R01DA034086-01
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Injection drug users (IDUs) constitute 60% of the approximately 5 million people in the U.S. infected with hepatitis C virus (HCV). HCV treatment leading to sustained viral response (SVR) is associated with increased survival. However, IDUs have had poor access to HCV care and their success in HCV treatment has been limited. With direct-acting antiviral agents, HCV treatment delivered within large clinical trials leads to SVR or cure in over 70% of genotype-1 infected patients, compared to 45% with previous therapies. However, SVR rates are as low as 14% in real-world settings. The majority of patients who fail to achieve SVR will develop drug resistance, but the optimal adherence level to minimize resistance is unknown. If HCV treatment continues to be delivered within current models of care, most IDUs will not only fail treatment and develop resistance, but may transmit resistant viruses to others. We have previously developed a multidisciplinary model of HCV care which integrates on-site primary care, substance abuse treatment, psychiatric care, and HCV-related care within opiate agonist treatment clinics. To maximize treatment outcomes, we piloted two models of intensive HCV-related care: directly observed therapy (DOT), and concurrent group therapy (CGT). In our DOT model, pegylated interferon is administered once weekly, if applicable, and one daily dose of oral medication is administered at the methadone window. In our CGT model, patients initiate HCV treatment within a once weekly treatment group which provides powerful social support to mitigate fears of side effects, promote efficient education, and deliver weekly injections, if applicable. It is unknown whether either model is better or more cost-effective than standard on-site care. PREVAIL 1: In the proposed study, 150 IDUs with chronic HCV (genotype 1) will be recruited from methadone clinics and randomized to one of three models of care: DOT; concurrent group treatment; or standard on-site care. Our specific aims are: 1) To determine whether either of two intensive on-site HCV treatment models (DOT or concurrent group treatment) is more efficacious than standard on-site treatment for enhancing adherence and SVR, and decreasing drug resistance; (2) To determine the incidence and factors associated with the development of drug resistance in IDUs; (3) To perform cost and cost-effectiveness analyses of each model; (4) To examine the impact of HIV coinfection on adherence and virologic outcomes among HCV-infected IDUs. PREVAIL 2: In the proposed study, 60 IDUs with chronic HCV (genotypes 1 2, 3 and 4) will be recruited from opiate agonist treatment programs and started on HCV treatment. Subjects will be offered the choice of model of care (either standard on-site, DOT, or concurrent group treatment). Our specific aims are: (1) to determine rates of adherence and SVR in a cohort of opiate agonist treatment patients initiating treatment with sofosbuvir-based regimens and (2) to determine adherence rates over time in drug users (genotype 3 and genotype 1 / IFN-ineligible) initiating a 24 week IFN-free regimen. PREVAIL 3: In the proposed study, 60 IDUs with chronic HCV (genotype 1 and 4) will be recruited from opiate agonist treatment programs and started on HCV treatment. Subjects will be offered the choice of model of care (either standard on-site, DOT, or concurrent group treatment). Our specific aims are: (1) to determine rates of adherence and SVR in a cohort of opiate agonist treatment patients initiating treatment with oral DAA combination of sofosbuvir and simeprevir or fixed dose of sofosbuvir and ledipasvir and (2) to determine adherence rates over time in drug users.

Conditions

Hepatitis C; Medication Adherence

Keywords

addiction; Adherence (attribute); Adverse effects; Agonist; Antiviral Agents; arm; base; care delivery; Caring; Chronic Hepatitis C; Clinic; Clinical Trials; Complex; Computer Simulation; cost; cost effective; cost effectiveness; Data; Development; Directly Observed Therapy; Disease; Dose; Drug resistance; drug resistant virus; Educational aspects; Epidemic; experience; Frequencies (time pattern); Fright; Genotype; Group Therapy; Health Care Costs; Health Personnel; Healthcare Systems; Hepatitis C; Hepatitis C Prevalence; Hepatitis C Transmission; Hepatitis C virus; HIV; Homelessness; improved; Incidence; Infection; Injecting drug user; Injection of therapeutic agent; Intensive Care; Interferons; Intervention; Knowledge; Life; Liver diseases; Liver Failure; liver transplantation; Living Costs; Mental disorders; Methadone; methadone clinic/center; Modeling; Mortality Vital Statistics; Motivation; multidisciplinary; Opiates; Oral; Outcome; Patients; Persons; Pharmaceutical Preparations; Physicians; pill (pharmacologic); Play; Poverty; Primary Health Care; programs; Psychiatric therapeutic procedure; psychosocial; Publishing; Quality-Adjusted Life Years; Randomized; Randomized Controlled Trials; randomized trial; Recruitment Activity; Regimen; Resistance; Resistance development; response; Risk; risk perception; Role; Site; skills; Social support; standard care; substance abuse treatment; success; Time; Treatment outcome; Treatment Protocols; treatment site; Trust; United States; Viral; Virus

Outcome Measures

Primary Outcomes (1)

• Electronically Monitored Medication Adherence

  Hepatitis C medication adherence will be measured using electronic blister pack monitoring.

  1-12 weeks

Secondary Outcomes (2)

• Sustained Virologic Response

  12 weeks after treatment completion

• HCV Treatment Completion

  Up to 48 weeks

Study Arms (3)

Modified Directly Observed Therapy (mDOT)

EXPERIMENTAL

In our mDOT model, pegylated interferon is administered once weekly, and one daily dose of oral medication is administered at the methadone window.

Other: Intensive Models (mDOT and CGT) of HCV Care

Concurrent Group Treatment (CGT)

EXPERIMENTAL

In our CGT model, patients initiate HCV treatment within a once weekly treatment group which provides social support to mitigate fears of side effects, promote efficient education, and deliver weekly injections.

Other: Intensive Models (mDOT and CGT) of HCV Care

Treatment as Usual

ACTIVE COMPARATOR

In the TAU arm, subjects will receive all medications monthly (or more often as needed) at the clinic.

Other: Intensive Models (mDOT and CGT) of HCV Care

Interventions

Intensive Models (mDOT and CGT) of HCV Care OTHER

Modified Directly Observed therapy (mDOT) and concurrent group treatment (CGT) are on-site HCV treatment models.

Concurrent Group Treatment (CGT); Modified Directly Observed Therapy (mDOT); Treatment as Usual

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HCV-infected, Genotype-1
• Treatment naïve or treatment experienced patients
• Willing to receive HCV treatment on-site
• Initiating treatment with direct-acting antiviral agents (DAA) with or without ribavirin +/- pegylated interferon alfa-2a
• Receiving methadone or buprenorphine in clinic at least one time per week
• Age 18 or older
• Able to provide informed consent
• Psychiatrically stable
• English or Spanish speaking
• Currently enrolled in a methadone or buprenorphine treatment program in the designated clinics in the Bronx (Melrose, Port Morris, Waters Place)

You may not qualify if:

• Known hypersensitivity (allergy) to interferon, ribavirin or DAA
• Psychiatrically unstable
• Pregnant or breast-feeding
• PREVAIL 2:
• HCV-infected, Genotype-1, , 2, 3, or 4
• Willing to receive HCV treatment on-site at an opiate agonist treatment program.
• Initiating treatment with sofosbuvir and ribavirin +/- pegylated interferon alfa-2a
• Age 18 or older
• Able to provide informed consent
• English or Spanish speaking
• Currently a patient in one of the designated clinics in the Bronx (Melrose, Port Morris, Waters Place)
• Known hypersensitivity (allergy) to interferon, ribavirin or sofosbuvir
• Pregnant or breast-feeding
• PREVAIL 3:
• HCV-infected, Genotype-1 or 4

Sponsors & Collaborators

• Prisma Health-Upstate: lead
• Clemson University: collaborator
• Albert Einstein College of Medicine: collaborator

Study Sites (1)

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

Related Publications (4)

• Heo M, Pericot-Valverde I, Rennert L, Akiyama MJ, Norton BL, Gormley M, Agyemang L, Arnsten JH, Litwin AH. Hepatitis C Virus Direct-Acting Antiviral Treatment Adherence Patterns and Sustained Viral Response Among People Who Inject Drugs Treated in Opioid Agonist Therapy Programs. Clin Infect Dis. 2021 Dec 6;73(11):2093-2100. doi: 10.1093/cid/ciab334.

  PMID: 33876230 DERIVED

• Pericot-Valverde I, Heo M, Akiyama MJ, Norton BL, Agyemang L, Niu J, Litwin AH. Factors and HCV treatment outcomes associated with smoking among people who inject drugs on opioid agonist treatment: secondary analysis of the PREVAIL randomized clinical trial. BMC Infect Dis. 2020 Dec 4;20(1):928. doi: 10.1186/s12879-020-05667-3.

  PMID: 33276738 DERIVED

• Akiyama MJ, Norton BL, Arnsten JH, Agyemang L, Heo M, Litwin AH. Intensive Models of Hepatitis C Care for People Who Inject Drugs Receiving Opioid Agonist Therapy: A Randomized Controlled Trial. Ann Intern Med. 2019 May 7;170(9):594-603. doi: 10.7326/M18-1715. Epub 2019 Apr 9.

  PMID: 30959528 DERIVED

• Akiyama MJ, Agyemang L, Arnsten JH, Heo M, Norton BL, Schackman BR, Linas BP, Litwin AH. Rationale, design, and methodology of a trial evaluating three models of care for HCV treatment among injection drug users on opioid agonist therapy. BMC Infect Dis. 2018 Feb 9;18(1):74. doi: 10.1186/s12879-018-2964-5.

  PMID: 29426304 DERIVED

MeSH Terms

Conditions

Hepatitis C; Medication Adherence; Behavior, Addictive; Hepatitis C, Chronic; Directly Observed Therapy; Disease; Infections; Liver Diseases; Liver Failure; Mental Disorders; Virus Diseases

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Hepatitis, Viral, Human; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Digestive System Diseases; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior; Compulsive Behavior; Impulsive Behavior; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hepatic Insufficiency

Results Point of Contact

• Title: Dr. Claire Stam - Director, Addiction Medicine Center
• Organization: Prisma Health

claire.stam@prismahealth.org

(864) 979-6749

Study Officials

• Garland Gudger, MD, MPH

  Prisma Health-Upstate

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2013
• First Posted: May 20, 2013
• Study Start: October 1, 2013
• Primary Completion: April 30, 2017
• Study Completion: April 30, 2017
• Last Updated: February 3, 2025
• Results First Posted: February 3, 2025

Record last verified: 2018-06

Locations

US (1)