Clinical trial NCT01857245: Intensive Models of HCV Care for Injection Drug Users
Official title: Intensive Models of HCV Care for Injection Drug Users
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Lead sponsor: Prisma Health-Upstate
Sponsor class: OTHER
Collaborators: name: Clemson University
name: Albert Einstein College of Medicine
First posted: 2013-05-20
Enrollment: 150
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: 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.

Detailed description: 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.

Eligibility criteria: Eligibility Ages Eligible for Study: 18 Years and older Genders Eligible for Study: Both

PREVAIL 1:

Inclusion Criteria:

* 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)

Exclusion Criteria:

* Known hypersensitivity (allergy) to interferon, ribavirin or DAA
* Psychiatrically unstable
* Pregnant or breast-feeding

PREVAIL 2:

Inclusion Criteria:

* 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)

Exclusion Criteria:

* Known hypersensitivity (allergy) to interferon, ribavirin or sofosbuvir
* Pregnant or breast-feeding

PREVAIL 3:

Inclusion Criteria:

* HCV-infected, Genotype-1 or 4
* Willing to receive HCV treatment on-site at an opiate agonist treatment program.
* Initiating treatment with oral DAA combination of sofosbuvir and simeprevir or fixed dose of sofosbuvir and ledipasvir.
* 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)

Exclusion Criteria:

* Known hypersensitivity (allergy) to sofosbuvir, simprevir or ledipasvir.
* Pregnant or breast-feeding

PREVAIL 4

Inclusion Criteria:

* 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
* Age 18 or older
* Able to provide informed consent
* Psychiatrically stable
* English or Spanish speaking

Exclusion Criteria:

* Known hypersensitivity (allergy) to interferon, ribavirin or DAA
* Psychiatrically unstable
* Pregnant or breast-feeding

Primary outcomes:
measure: Electronically Monitored Medication Adherence
timeFrame: 1-12 weeks
Secondary outcomes:
measure: Sustained Virologic Response
timeFrame: 12 weeks after treatment completion
measure: HCV Treatment Completion
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
Study officials:
affiliation: Prisma Health-Upstate
name: Garland Gudger, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.