Intensive Models of HCV Care for Injection Drug Users

Study Overview
=================
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.

Official Title
-----------------
Intensive Models of HCV Care for Injection Drug Users

Conditions
-----------------
Hepatitis C, Medication Adherence

Intervention / Treatment
-----------------
* Other: Intensive Models (mDOT and CGT) of HCV Care


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Modified Directly Observed Therapy (mDOT)<br>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<br>* Modified Directly Observed therapy (mDOT) and concurrent group treatment (CGT) are on-site HCV treatment models.<br>|
| Experimental: Concurrent Group Treatment (CGT)<br>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<br>* Modified Directly Observed therapy (mDOT) and concurrent group treatment (CGT) are on-site HCV treatment models.<br>|
| Active Comparator: Treatment as Usual<br>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<br>* Modified Directly Observed therapy (mDOT) and concurrent group treatment (CGT) are on-site HCV treatment models.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Electronically monitored medication adherence | Hepatitis C medication adherence will be measured using electronic blister pack monitoring. | 12-24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatitis C viral load. |  | 12 weeks after treatment completion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Oral, Opiates, 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, 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