Clinical trial NCT03093415
Conditions: Hepatitis C Substance Use Disorders Substance Abuse, Intravenous
Keywords: Hepatitis C HCV People Who Inject Drugs PWID Medication Assisted Therapy MAT Needle Exchange Program
Sponsor: Oregon Health and Science University
Start date: 2017-05-30; Completion date: 2019-06-06
Enrollment: 100 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
hepatitis C virus (HCV) has traditionally been treated in subspecialty health centers given the complexity of older pegylated interferon containing regimens, formerly the standard of care. This model has persisted into the modern era of direct anti-viral agents (DAAs) despite their relative simplicity, creating a bottleneck of human resources necessary to fight the largest infectious epidemic in North America. In addition, stigma and fear over cost has lead payers to restrict treatment in People Who Inject Drugs (PWIDs), even though a majority of new infections occur in this population.

This study evaluates the effectiveness of treatment of HCV with elbasvir-grasoprevir in PWIDs in a real world, community health clinic setting.

There are two prospective cohorts of PWIDs of 25 patients each, both in primary care-based community health clinics in Portland, Oregon. Cohort one is actively engaged with ambulatory medication assisted therapy with buprenorphine or extended released injectable naltrexone. Cohort two maintains active injection drug use with needle exchange and risk reduction education.

These groups are compared to a 50 patient retrospective cohort of people with substance use disorders at tertiary care hepatology-based treatment program.

All patients have genotype 1 or 4 HCV and are treated with elbasvir-grasoprevir for 12 weeks.

The investigators hypothesize there is no difference in sustained viremic response at 12 or 48 weeks post-completion of treatment (SVR 12, 48) when treating patients in a community health clinic setting as compared to the standard-of-care subspecialty setting.

Detailed description:
Hepatitis C has traditionally been treated in subspecialty health centers given the complexity of older pegylated interferon containing regimens, formerly the standard of care. This model has persisted into the modern era of direct anti-viral agents (DAAs) despite their relative simplicity, creating a bottleneck of human resources necessary to fight the largest infectious epidemic in North America. In addition, stigma and fear over cost has lead payers to restrict treatment in People Who Inject Drugs (PWIDs), even though a majority of new infections occur in this population.

This study evaluates the effectiveness of treatment of hepatitis C virus (HCV) with elbasvir-grasoprevir in people who inject drugs (PWIDs) in a real world, community health clinic setting.

There are two prospective cohorts of PWIDs of 25 patients each, both in primary care-based community health clinics in Portland, Oregon. Cohort one is actively engaged with ambulatory medication assisted therapy with buprenorphine or extended released injectable naltrexone. Cohort two maintains active injection drug use with needle exchange and risk reduction education.

These groups are compared to a 50 patient retrospective cohort of people with substance use disorders at tertiary care hepatology-based Academic Health Center.

All patients have genotype 1 or 4 HCV and are treated with elbasvir-grasoprevir for 12 weeks. The investigators exclude patients who: are under the age of 18; have a history of liver transplant; have failed past treatment of HCV; have an Aspartate aminotransferase Platelet Ratio Index (APRI) \> 0.7 or APRI \>0.7 but fibrosure/fibroscan of F2 or less; patients with genotype 1a and Nonstructural 5a (NS5a) resistance associated variants (RAVs); have clinical or radiologic evidence of cirrhosis; have aminotransferase levels \>10x upper limit of normal; have a hemoglobin of less than 11g/dL, and are co-infected with hepatitis B or HIV.

The investigators hypothesize there is no difference in sustained viremic response at 12 or 48 weeks post-completion treatment (SVR 12, 48) when treating patients with a DAA in a community health clinic setting as compared to the standard-of-care subspecialty setting.

Arms: arm 1: 25 People Who Inject Drugs engaged in a Medication Assisted Therapy treatment program for their substance use disorder, treated for their HCV using elbasvir-grazoprevir (50 mg/100 mg) for 12 weeks. arm 2: 25 People Who Inject Drugs engaged in a Needle Exchange Program with risk reduction education, treated for their HCV using elbasvir-grazoprevir (50 mg/100 mg) for 12 weeks. arm 3: 50 people with substance use disorder and HCV engaged with an Academic Hepatology Clinic (Oregon Health \& Sciences University, OHSU) and treated with elbasvir-grazoprevir (50 mg/100 mg) for 12 weeks.
Interventions: intervention 1: elbasvir-grazoprevir (50 mg/100 mg)
Intervention descriptions: intervention 1: 12 week treatment of elbasvir-grazoprevir (50 mg/100 mg)

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 20 
 
Project Title:  
Hepatitis C Treatment in PWIDs: MAT or Syringe Exchange Assisted-therapy vs Standard 
of Care 
 
NCT Number: 
NCT03093415 
 
Last Review/Edits: 
January 20, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Page 2 of 20 
 
Protocol 1. 
Protocol Title 
Hepatitis C Treatment in PWIDs: MAT or Syringe Exchange Assisted-therapy vs Standard of Care  
IRB 16357 
2. Objectives/Hypothesis 
Hypothesis: Treatment adherence and hepatitis C (HCV) infection cure rates using a simple 1-pill a day regimen 
of a direct anti-viral agent (DAA) in two unique care delivery models for marginalized persons with HCV 
infection, Outside In needle exchange program serving people who inject drugs (PWID) and Old Town Clinic, an 
integrated multi-disciplinary primary care clinic serving homeless and low income adults, will be similar to HCV 
patients treated in a traditional Hepatology Clinic at an Academic Health Center 
Purpose: Determine if two unique safety net clinics (intervention group) with comprehensive behavioral health, 
pharmacy and medical services will improve HCV therapy adherence and reduce re-infection rates such that 
overall cure rates will be maintained and be similar to cure rates seen over the same time period in a traditional 
hepatology clinic setting (comparison group). The expectation is that these safety net clinics with 
comprehensive healthcare services should normalize the chaotic lifestyles of the patients that typically utilize 
safety net clinics. 
Goal: If this study can demonstrate that such well-established comprehensive multidisciplinary safety net clinics 
that see an extremely marginalized population that are typically excluded from access to HCV therapies can 
achieve similar HCV treatment responses as seen in traditional clinics, the use of such sites as HCV treatment 
centers can be utilized on a national scale.    
AIMS: 
1. Identify clients/subjects in each care setting with genotype 1 or 4 HCV infection >18 years of age that 
wish to be treated.  
a. Outside In Injection Drug Users Health Services (n=25) 
b. Old Town Clinic (n=25) 
c. Retrospective cohort of subjects at Oregon Health & Science University Hepatology Clinic (n=50) 
2. Prior to treatment each client/subject is administered a questionnaire assessing motivation, readiness 
for treatment 
3. Assess adherence to treatment regimen, laboratory testing, discontinuation rates, cure rates, and 
reinfection rates 1 year post treatment 
4. Compare results across the three care delivery sites and identify any patient-related variables that 
impact treatment success 
3. Background 
Since the introduction of the first DAAs to treat HCV about 2 years ago, there are compelling reasons for 
expanding access to treatment for all HCV patients including their safety and cost-effectiveness. 1 However, 
certain HCV populations such as the homeless and people who inject drugs (PWID) have a high prevalence of 
chronic HCV infection.  At the same time these populations have significant barriers to accessing care and have 
low rates of treatment initiation for their HCV infection. The impact of highly potent and well-tolerated 
interferon-free HCV treatment regimens will remain negligible as long as access to therapy cannot be expanded 
to the most affected risk groups. 


Page 3 of 20 
One strategy that addresses several barriers is co-localization or integrated care of HCV screening, evaluation, 
and treatment with other medical or social services. Co-localization has already been applied to settings with a 
high prevalence of HCV infection (e.g., correctional facilities and programs providing needle exchange, 
substance abuse treatment, and methadone maintenance) but is not uniformly available.   
One of the major obstacles to HCV care in the homeless and PWID is the lack of treatment settings that are 
suitably adapted for the needs of this vulnerable population. Nevertheless, HCV treatment has been delivered 
successfully to PWID through various multidisciplinary models such as community-based clinics, substance 
abuse treatment clinics, and specialized hospital-based clinics. Models may be integrated in primary care--all 
under one roof in either addiction care units or general practitioner-based models--or can occur in secondary or 
tertiary care settings. Additional innovative models include directly observed therapy and peer-based models.  
2,3,4 
This current study uses a mixed care model approach where two unique safety net sites, one serving the 
homeless and the low income and the other, active injection drug users who utilize a needle exchange program, 
working in concert with a traditional gastroenterology/hepatology clinic to identify and treat HCV patients 
within their own care environment. A unique feature of this study is maintaining a real world setting for HCV 
treatment to occur. Allowing therapy to be given in an environment that is familiar and supportive should foster 
adherence and high rates of treatment success. 
The results of this study will give insight into the feasibility of using safety net medical sites such as needle 
exchange programs and community health centers serving low income or homeless populations to safely and 
effectively treat this vulnerable population that is disproportionately affected by HCV infection. Furthermore, 
feedback from clients/patients using validated questionnaires could identify modifiable barriers to treatment 
success. Findings from this study could help expand the HCV treatment capacity beyond subspecialty practice 
and even the traditional primary care clinic. 
4. Study Design 
Study Objectives 
Primary Objective: Determine if the clinical effectiveness of Zepatier  in treating patients with HCV infection and 
mild fibrosis in two safety net sites, which offer comprehensives services to normalize the chaotic lifestyles of 
people who inject drugs and the homeless, is similar to what is expected in a tertiary hepatology clinic that cares 
for a more traditional patient population. 
Secondary Objective: Identify client/patient factors that impact HCV treatment success in this population 
Study Endpoints 
Primary Endpoint 
• 
Sustained virologic response rates measured at 12 weeks post treatment (SVR12)-Intention to Treat 
analysis (taking into account treatment discontinuation and failure rates) 
• 
Persistently HCV infection free after 48 weeks of treatment cessation (SVR48) 
Secondary Endpoints 
• 
Adherence determined by client/subject self-reported medication adherence measured by percentage 
of pills taken on a monthly basis, as well as compliance with laboratory testing 


Page 4 of 20 
• 
Treatment discontinuation rates including loss to follow up 
• 
Percent of genotype 1a patients with baseline NS5A resistance 
Relapse with substance use disorder in Old Town Clinic setting 
Exploratory analysis of potential client/subject factors impacting readiness for treatment, non-adherence, or 
reinfection based on questionnaires administered at baseline and at 48 weeks post treatment 
Study Design 
This will be a prospective study at the two safety net clinic sites where 25 non-cirrhotic subjects at each site will 
receive HCV treatment with Zepatier. Patients will be followed by a care team comprised of a medical provider 
and pharmacist at each care site within their own medical home environment. Subjects will be monitored for 
treatment and lab adherence. Overall SVR 12 will be assessed for this study group. This SVR12 rate will be 
compared to the SVR12 rate of a retrospective cohort of 50 consecutive non-cirrhotic HCV patients treated in 
the Hepatology Clinic at Oregon Health and Science (OHSU) starting in 2015. A prospective cohort will not be 
necessary at OHSU, since SVR12 rates have been consistently within the range of what has been reported in the 
literature.  
Study Definitions 
Treatment failure - 
• 
Primary treatment failure: detectable HCV RNA at week 12 post-treatment. 
• 
Secondary treatment failure: despite achieving SVR12, detectable HCV RNA at 48-week follow-up 
posttreatment. This would suggest re-infection, if there is evidence of re-exposure to virus. In addition, 
repeat genotyping will be performed in order to determine if the genotype has changed from baseline. If 
so, this would also suggest re-infection. 
Treatment discontinuation- therapy interrupted by either the subject due to compliance issues/side effects or by 
medical provider due to safety issues. 
Reinfection- achieved SVR12, but at 48 weeks after completing HCV therapy HCV RNA is detected. If there is 
evidence of re-exposure to HCV infection and/or repeat genotyping demonstrates a different genotype from 
baseline genotype prior to starting HCV therapy.  
Treatment Regimen Compliance - 
• 
Medication Compliance- percentage of pills taken during 12-week therapy. Pill count is assessed at every 
clinic visit. 
• 
Laboratory Compliance- percentage of completed scheduled lab draws 
• 
Clinic Visit Compliance- percentage of attended scheduled clinic visits 
5. Study Population 
 
a. Number of Subjects 
A total of 50 retrospective subjects will be enrolled at OHSU. Two separate prospective cohorts of 25 
patients each will be enrolled at Old Town Clinic and Outside In, prospectively.  


Page 5 of 20 
 
b. Inclusion and Exclusion Criteria 
Prospective Study Cohort 
Consecutive clients/patients with documented chronic hepatitis infection (detectable HCV RNA) seen at 
one of the study sites that are interested in HCV treatment and fulfill inclusion/exclusion criteria will be 
enrolled. Each site will determine readiness for treatment. Final approval for treatment initiation and 
ongoing monitoring during treatment will be under the supervision of the medical provider panel led by 
Dr. Zaman.  
Retrospective Study Cohort 
The Electronic Medical Record of the OHSU hepatology clinic will be reviewed and patients treated for 
hepatitis C with Zepatier selected in a retrospective, sequential fashion, starting at the time of closure of 
enrollment at the two prospective sites.  
Screening Data Disposition 
All data collected during screening for patients not meeting inclusion criteria, or meeting exclusion 
criteria, will be destroyed immediately, EXCEPT for the reason for exclusion, which will be collected and 
saved in a de-identified manner until study completion for the purposes of establishing external validity.  
Inclusion Criteria 
1) Genotype 1b and genotype 1a without baseline NS5A resistance or Genotype 4 
2) APRI Score <0.7; if >0.7 a Fibrosure/Fibrotest or Fibroscan score of F2 or less, plus no clinical or 
laboratory evidence of cirrhosis 
3) Readiness for treatment based on ability to make >2/3 sequential office visits either prospectively 
retrospectively.  
4) Patients must be assessed to have decision-making capacity, be capable of consenting, and not be 
displaying evidence of overt intoxication.  
Exclusion Criteria 
1) Previously treatment for hepatitis C infection 
2) Clinical, radiologic, or laboratory evidence of cirrhosis 
3) Hepatocellular carcinoma, HIV or hepatitis B virus co-infection, elevated prothrombin time 
unrelated to anticoagulation, hemoglobin level less 11 g/dL, platelet count <150 × 109 cells/L), WBC 
<4.0 x103/mm3 , aminotransferase levels more than 10 times the upper limit of normal, or albumin 
level <3.0 g/L, positive office-based pregnancy test. 
4) Subjects taking medications that are contra-indicated to administer with Zepatier including 
phenytoin, carbamazepine, rifampin, St. John’s Wort, and cyclosporine. Study pharmacists will 
assess drug interactions. 5) Persons under the age of 18 


Page 6 of 20 
 
c. Vulnerable Populations 
All of our subjects enrolled prospectively will suffer from a substance abuse disorder but will only be 
eligible for consent/enrollment if they are assessed to have decision-making capacity at the time of 
consent. As such, these subjects do not meet NBAC criteria of a vulnerable population. Neither of the 
study sites serves subjects who are currently incarcerated, so prisoners will not be asked to consent for 
the study. In the event that one or our fully consented subjects becomes incarcerated during the course 
of treatment, arrangements will be made for Zepatier and standard-of-care laboratory monitoring to be 
continued while incarcerated. However, optional procedures, such as interviews and surveys, will not be 
continued during a subjects incarceration to avoid potential inducement to participate.  Zepatier is 
contraindicated in pregnancy, therefore pregnant women will not be included in the study. Children are 
also not eligible to participate.   
 
d. Setting.  
This is a multi-site study with both prospective arms of the study operated on OHSU-affiliated but not  
OHSU-owned properties. Site leaders will be OHSU faculty and all other principle personnel will be 
OHSU-affiliated and CITI-trained in concordance with OHSU IRB requirements. All sites will be relying 
upon the OHSU IRB for study oversight.  
Outside In Needle Exchange Program 
Outside In is a Federally Qualified Health Center and a Healthcare for the Homeless clinic in Portland  
Oregon.  Its mission is to help homeless youth and other marginalized populations move towards health 
and self-sufficiency.  The medical clinic served as a patient centered primary care home for 6000 people 
in 2015 providing primary and acute care,  naturopathic care in both a fixed location and from outreach 
medical vans throughout the metropolitan region.  Roughly 50% of Outside In’s primary care patients 
report homelessness and more than 80% of its patients are at or below the Federal Poverty Line.  
Outside In also is home to the United States’ first publicly funded needle exchange program.  This 
program began in 1989 and serves over 4,500 unique clients annually. In FY 2015 Outside In’s syringe 
exchange program conducted 144 Rapid HCV antibody tests with 27% of the tests coming back reactive 
for HCV antibodies. In July 2013 when Oregon liberalized its law regarding secondary prescription of 
naloxone to reduce opiate overdose, Outside In started Oregon’s first and only Naloxone training and 
distribution program that year. After one year of operation the Multnomah County Health Department 
reported a 29% reduction in heroin overdose deaths which it credited to that program. Since the start of 
that program Outside In has conducted over 1400 individual trainings with prescriptions, to active 
injection drug users and their supports, and has received over 934 self-reports of overdose reversals. 
Outside In operates two mobile medical vans which it sends with complete provider care teams 
including medical and behavior health clinicians to remote homeless sites and other health disparity 
locations such as community mental health facilities. It operates a satellite syringe exchange at one of its 
most productive homeless  outreach sites. Outside In’s main clinic facility is located on the southwest 
end of downtown Portland, (OTC is in the northwest end) where the four main homeless youth serving 
agencies are located. Outside In has extensive homeless youth transitional services including housing, 
case management , job training and an alternative school. Outside In operates a tattoo removal program 
for gang-involved and street-involved people. At its main facility Outside In offers acupuncture, massage 
and chiropractic care. Outside In is a state certified patient-centered primary care home, providing 
integrated behavioral health care within its primary care through co-located interdisciplinary teams 
sharing a panel of patients. We offer same day access which is essential in serving their transient and 
high-risk patient population. 


Page 7 of 20 
The overall goal of Outside In’s HCV treatment program is to improve the care of its patients suffering 
from chronic Hepatitis C virus and to standardize the screening, diagnosis, work-up, and treatment of 
this condition throughout Outside In.  Patient-centered design to increase success in the recruitment 
and treatment of actively using, homeless or high-risk patients is at the core of the creation of this 
program.  Essential parts of Outside In’s program include recruitment and referral from Outside In’s 
syringe exchange program as well as referral by the primary care provider (PCP) from within our 
homeless health services, initial office visit and assessment with an Outside In HCV provider, tailored 
weekly or bi-weekly medication dispensing, bi-weekly clinical pharmacist visits, monthly lab monitoring, 
and optional participation in HCV harm-reduction/ re-infection prevention education sessions.  All of 
these services are provided at Outside In, the patients’ primary care medical home.  
Old Town Clinic 
Old Town Clinic (OTC) is part of Central City Concern (CCC), a multi-faceted social service agency whose 
mission is to provide comprehensive solutions to ending homelessness and achieving self-sufficiency.  
Old Town Clinic is a Federally Qualified Health Center and a Healthcare for the Homeless clinic located in 
downtown Portland, Oregon.  This is an integrated, multi-disciplinary primary care clinic serving over 
4,900 homeless and low-income adults living with a broad range of social, behavioral, and medical 
conditions.  More than 70% of OTC patients are homeless and 99% are at or below 100% of the federal 
poverty level.  The population of Old Town Clinic has a high prevalence of chronic hepatitis C infection.  
In addition, the patient population has a high prevalence of severe and persistent mental illness, 
addiction, and chronic medical illness.  For these reasons, many of its patients are not currently 
candidates for chronic hepatitis C treatment, and even if they are candidates, the barriers to receiving 
treatment are insurmountable.  The consequences of which are not insignificant as 24% of its patients 
are known to suffer from chronic hepatitis C, and among patients with the most advanced illness, the 
known prevalence is 56%.  The morbidity and mortality of chronic hepatitis C infection as well as the 
costs to the healthcare system have been well described. 
OTC is a patient centered medical home and offers many integrated services that help support our 
patients’ health with the goal of increasing their overall wellness.  Specifically, we have an onsite and 
fully integrated clinical pharmacy program.  The pharmacy dispenses medications for the majority of our 
patients, many of whom struggle with medication adherence.  To address this our pharmacy offers 
medical therapy management consultations, bubble packing of medications, medication box 
management, and daily dispensing of medication as needed.  Clinical pharmacy is also integrated with 
our direct patient care teams and has improved many difficult to manage chronic disease states.  For 
example, we have a diabetes management program that has shown great adherence and improved 
diabetes control in our patients.  As well, our clinical pharmacists help to treat patients suffering from 
schizophrenia and psychosis by managing and administering long acting injectable anti-psychotic 
medications.  Leveraging our clinical pharmacy services to treat patients suffering from chronic HCV 
would strengthen patient adherence and their overall treatment experience. 
Mental health is also fully integrated into our primary care services.  There are psychiatric nurse 
practitioners and licensed clinical social workers on each care team to offer diagnosis and management 
recommendations as well as counseling services.  For patients suffering from severe and persistent 
mental illness, OTC coordinates care with a co-located specialty mental health program that offers more 
intensive behavioral health support including case management.  Access to these mental health services 
will be essential for patients undergoing hepatitis C treatment who are often afflicted with mental illness 
and trauma. 


Page 8 of 20 
Another unique offering at OTC is fully integrated Alcohol and Drug treatment services within primary 
care.  We offer level 1 outpatient treatment for individuals suffering from opioid use disorder and others 
who suffer from comorbid chronic pain and substance use disorders.  We have a robust medication 
assisted treatment program housed within primary care.  Specifically, we offer buprenorphine and 
longacting naltrexone in conjunction with mandatory group and individual counseling sessions.  These 
patients are some of the most adherent of the OTC population because the A&D program requires this 
(i.e. twice weekly groups, weekly medication dispensing, etc.).  This population (i.e. PWIDs or have a 
history of IVDU) is disproportionately affected by HCV, so having this recovery support will not only 
improve treatment adherence but will reduce the risk of HCV re-infection. 
The overall goal of OTC’s HCV treatment program is to improve the care of its patients suffering from 
chronic Hepatitis C virus and to standardize the screening, diagnosis, work-up, and treatment of this 
condition throughout OTC.  Patient-centered design is at the core of the creation of this program.  
Patient and provider co-design, utilizing human-centered design principles and tools, has been central to 
its development.   
Essential parts of OTC’s program include referral by the primary care provider (PCP), initial office visit 
and assessment with an OTC HCV provider, weekly medication dispensing, bi-weekly clinical pharmacist 
visits, monthly lab monitoring, referral to medication assisted treatment or mental health services as 
indicated, and optional participation in education and peer support sessions.  These sessions will be 
initially modeled after previously validated peer support groups for treatment with interferon-based 
regimens,3,5 and further refined through our iterative, human-centered design process. Patients who are 
recent (previous 12 months) or current injection drug users will be strongly encouraged, but not 
required, to meet weekly in groups of less than 12 individuals, facilitated by certified drug and alcohol 
counselors. Patients electing to attend HCV health education sessions will partake in a 1 hour, certified 
health educator-lead, interactive hepatitis C education session, focusing on medical and social aspects of 
the disease, adherence, and re-infection prevention. Integrative HCV Treatment Model At Two Study 
Sites 
Outside In HCV Treatment Program 
Essential parts of Outside In’s program include recruitment and referral from Outside In’s syringe 
exchange program or referral by the primary care provider (PCP) from within our homeless health 
services, initial office visit and assessment with an Outside In HCV provider, tailored weekly or bi-weekly 
medication dispensing, bi-weekly clinical pharmacist visits, monthly lab monitoring, and optional 
participation in HCV harm-reduction/ re-infection prevention education sessions.  All of these services 
are provided at Outside In, the patients’ primary care medical home.  
• 
The medical clinic serves as a patient centered primary care home providing primary and acute 
care, naturopathic care in both a fixed location and from outreach medical vans throughout the 
metropolitan region. 
• 
Outside In is home to United States’ first publicly funded needle exchange program.   
• 
The organization runs two medical vans it sends with complete provider care teams including 
medical and behavior health clinicians to remote homeless sites and other locations with 
extensive health disparities such as community mental health facilities. 
• 
Outside In is a state certified patient-centered primary care home, providing integrated 
behavioral health care within its primary care through co-located interdisciplinary teams sharing 
a panel of patients. 


Page 9 of 20 
Old Town Clinic HCV Treatment Program 
Old Town Clinic (OTC) is part of Central City Concern (CCC), a multi-faceted social service agency whose 
mission is to provide comprehensive solutions to ending homelessness and achieving self-sufficiency.  
Essential parts of OTC’s HCV program include referral by the primary care provider (PCP), initial office 
visit and assessment with an OTC HCV provider, weekly medication dispensing, bi-weekly clinical 
pharmacist visits, monthly lab monitoring, referral to medication assisted treatment or mental health 
services as indicated, and optional participation in education and peer support sessions.   
Onsite and fully integrated clinical pharmacy program.  The pharmacy dispenses medications for the 
majority of patients, many of whom struggle with medication adherence.  To address this the pharmacy 
offers medical therapy management consultations, bubble packing of medications, medication box 
management, and daily dispensing of medication as needed.  
Mental health is fully integrated into our primary care services.  Psychiatric nurse practitioners and 
licensed clinical social workers on each care team offer diagnosis and management recommendations as 
well as counseling services.  For patients suffering from severe and persistent mental illness, OTC 
coordinates care with a co-located specialty mental health program that offers more intensive 
behavioral health support including case management.   
OTC has fully integrated Alcohol and Drug treatment services within primary care.  They offer level 1 
outpatient treatment for individuals suffering from opioid use disorder and others who suffer from 
comorbid chronic pain and substance use disorders.  Because of this, these patients are some of the 
most adherent of the OTC population because the A&D program requires this (i.e. twice weekly groups, 
weekly medication dispensing, etc.). 
 
e. Recruitment Methods, by site, estimated to take 2-3 months. 
Old Town Clinic. Upon study initiation, the site principle investigator will pull a list of active patients in 
the Old Town Clinic buprenorphine-based Medication Assisted Program who also carry a diagnosis of 
chronic hepatitis C. In addition, patients requiring level 2 intensive outpatient substance use treatment 
receiving methadone or buprenorphine-based Medication Assisted Therapy with co-morbid chronic 
hepatitis C will be pulled by chart study coordinator chart review. Anyone not meeting the inclusion 
criteria or with automatic exclusion criteria will be excluded.  The study coordinator will then contact the 
remaining patients in a sequential fashion via telephone with the following script: “Hello I’m _____ a 
____ at Old Town Clinic. We are looking for patients in the Suboxone program at Old Town interested in 
treating their hepatitis C. We cannot guarantee it without a doctors visit, but we may be able to treat 
your hepatitis C. Would you like to make an appointment to be screened?” We will also post fliers in the 
meeting rooms stating, “Are you Hepatitis C Positive? Are you interested in treatment? Old Town Clinic 
is part of a study working to treat people with HCV. For more information and to see if you qualify for 
this study, please call 971-XXX-XXXX”. The first 25 patients that agree to be screened, meet criteria, and 
sign an informed consent to enroll in the study will be enrolled. Subjects will be reimbursed for each 
survey or in-depth interview with a $15 Fred Meyer gift card.  
Outside In.  Upon the study initiation, Outside In’s Injection Drug Users Health Services Program will 
begin handing out fliers to all clients of the syringe exchange program as well as posting fliers on the 
bulletin board in the waiting room. These fliers will read, “Are you Hepatitis C Positive? Are you 
interested in treatment? Outside In is part of a study working to treat people with HCV. For more 
information and to see if you qualify for this study, please call 503-535-XXXX”. This outreach process will 
be augmented with a respondent-driven sampling method called “snowball sampling,” which uses social 
networks to find more clients in hard to reach populations. Representative seed subjects will be given 


Page 10 of 20 
three coupons (fliers) to be given to other syringe exchange clients who also might be treatment 
candidates. Subjects may also be referred to study by their Outside In primary care provider. The phone 
line will be answered by the site coordinator and will have a voicemail that says “Thank you for your 
interest in our study. For this study, you need to be a current injection drug user. You must be over the 
age of 18. Please leave a name and a phone number you can be reached at. All calls will be returned the 
morning of the next business day. Thank you for your interest.” The site study coordinator will return 
the client’s call (two attempts will be made).  This staff will confirm the initial screening conditions, 
inquire about insurance status, and make a medical appointment if appropriate.  If the client is 
uninsured, he/she will be directed to OHP (Oregon Medicaid) enrollment and asked to re-engage with 
the study when insurance is active.  If the client is insured by OHP, an appointment will be made for the 
client to meet with a treating medical provider.  The provider appointment will serve as a medical 
screening visit to include missing baseline lab testing necessary to determine eligibility, the results of 
which will be helpful in determining inclusion.  The first 25 patients that agree to be screened, meet 
criteria, and sign an informed consent to enroll in the study will be enrolled. Subjects will be reimbursed 
for each survey or in-depth interview with a $15 Fred Meyer gift card. 
OHSU (Retrospective). The OHSU principle investigator, or IRB approved surrogate, will review the 
hepatology clinic Electronic Medical Record for patients treated for hepatitis C with Zepatier and select 
subjects in a retrospective, sequential fashion, starting at the time of closure of enrollment at the two 
prospective sites.  
 
f. 
Consent Process 
The consent coordinator will obtain consent during the intake appointment, after the initial screening 
process as detailed below. The consent coordinator will be an IRB-approved, OHSU affiliated employee 
of the study site, with 50% of their FTE covered by grant funding. This will occur in person, in a 
confidential clinic exam room, with ample time for questions and clarifications. The consent form will 
also be provided prior to the appointment so subjects have time to read over it and highlight any 
questions or concerns they may have. Subjects with low self-reported reading literacy will have the 
consent form read to them with a teach-back to confirm understanding. While all study coordinators will 
be employees of their parent organizations and will have access to the medical record, they will not be 
medical providers with a long standing relationships with the subjects to minimize potential for coercion 
and conflicts of interest.  
For the purposes of this pilot study, only subjects who identify as proficient in the English language will 
be enrolled. The scientific rationale for this is based on a lack of validated non-English language 
questionnaires suiting our study question. In addition, the Medication Assisted Therapy population at 
the Old Town Clinic site of Central City Concern has only English speaking drug and alcohol counseling 
groups (present in East-Side Clinic, not participating in our study), potentially creating bias if non-English 
speaking patients were enrolled at the Outside In site.  
Consent will follow a clinic visit with a study provider, who will use a basic capacity assessment to 
determine eligibility to consent. This will include the following general principles of being able to 
understand, express a choice, appreciation, and reasoning.9 
6. Procedures Involved 
• 
The primary therapeutic intervention will be one tablet of Zepatier (elbasvir 50mg/grazoprevir 100mg) 
daily with or without food for 12 weeks. This dosage is consistent with current FDA approval for the 
treatment of hepatitis C.  


Page 11 of 20 
• 
Screening, treatment interventions, and follow up are outlined below. All of the following represent 
standard of care interventions, with the exception of survey data collection and in-depth qualitative 
interviews. These interviews serve the purpose of better understanding potential barriers to successful 
treatment and to identify potential mitigating innovations in the care of this complicated and neglected 
population. 
Treatment Scheme 
Baseline Testing (already performed as a part of standard of care for a patient with HCV infection) 
• 
CBC with differential, Complete Metabolic Profile, GFR, INR, HCV genotyping with NS5A resistance 
testing for genotype 1a, HCV RNA, HIV, pregnancy test in female of childbearing age 
• 
APRI score or Fibrosure or Fibroscan to determine fibrosis stage. APRI score is defined as AST level in 
IU/L over 40 IU/L (upper limit of normal value) divided by platelet count in 109/L multiplied by 100 
or. 
Screening Visit 
• 
Consent process including discussion of the consent form  
• 
History and physical to exclude signs and symptoms of cirrhosis 
• 
Inclusion and exclusion criteria assessed 
• 
NS5A resistance testing for genotype 1a subjects (subjects excluded if baseline resistance present)  
• 
Assess subject’s readiness for treatment: Subjects must have established care as a primary care 
patient at Outside In or Old Town Clinic. They must express a desire to be treated and to adhere to 
all laboratory monitoring and visit requirements.   
• 
Screen failure subjects will be linked to appropriate care within the study site or at OHSU hepatology 
for further management 
Visit 1 
• 
Clinic Visit 
• 
Once enrolled, completion of validated questionnaires (see Appendix that includes additional 
references) that assess the subject’s understanding of health, current health status, addiction and 
severity of addiction, social support, and degree of stigma. These assessments have been described 
in hepatitis C infected population.6,7,8 
Visit 2 
• 
Clinic visit 
• 
Verify the following studies/assessments are complete including CBC; INR, complete metabolic 
profile; GFR; genotype 1a, 1b, or 4 HCV RNA; no baseline RAVs for genotype 1a subjects 
• 
Verify Readiness for treatment 


Page 12 of 20 
• 
Verify questionnaires completed 
• 
Pregnancy counseling 
Visit 3 (Initiation of HCV treatment) 
• 
Clinic visit 
• 
Check in post-survey on subject well-being 
• 
Pharmacy dispenses 2 weeks, or less if indicated* of HCV medication  
*Given the complexity of this population, the study pharmacist and clinicians will determine the most 
appropriate dispense frequency and method depending on the subjects’ needs. 
Visit 4 (week 2 of HCV treatment) 
• 
Clinic Visit 
• 
Compliance assessment 
• 
Pharmacy dispenses another 2 weeks, or less if indicated, of HCV medication 
Visit 5 (week 4 of HCV treatment) 
• 
Clinic Visit 
• 
Compliance assessment 
• 
HCV RNA (if detectable, repeat HCV RNA in 6 weeks) 
• 
Pharmacy dispenses 2 weeks, or less, if indicated, of HCV medication 
Visit 6 (week 6 of HCV treatment) 
• 
Clinic Visit 
• 
Compliance assessment 
• 
Recheck HCV RNA in those subjects who had detectable HCV RNA at week 4. If on repeat 
testing at week 6, viral load has increased by 10 fold >1 log10 IU/mL discontinue therapy. Visit 7 (week 8 
of HCV treatment) 
• 
Clinic Visit 
• 
Compliance assessment 
• 
Check CMP. If liver enzymes >10 fold discontinue therapy 


Page 13 of 20 
VISIT 8 (week 12 of HCV therapy) - End of Treatment 
• 
Clinic Visit 
• 
Compliance assessment 
VISIT 9 (week 24) - 12 weeks after treatment completed 
• 
Clinic visit 
• 
HCV RNA to assess for SVR12, repeat genotype to clarify re-infection vs failure if + 
VISIT 10 (week 60) - 48 weeks after treatment completed 
• 
Clinic visit 
• 
HCV RNA to assess for SVR48, repeat genotype to clarify re-infection vs failure if + 
• 
Re-administer questionnaires 
TOTAL DURATION - about 18 months 
Quantitative Survey Data.  
The following surveys will be performed and have been submitted for IRB approval: 
• 
Chronic Illness Anticipated Stigma Scale (CIASS) 
• 
MOS Social Support Survey 
• 
SF-36 “Health and Well-Being” Survey 
In addition, in-depth qualitative interviews will be performed Interviews will cover salient issues in 
participants’ lives at the community, organizational, household levels, as well as relationships (friends, 
family and sexual partners) perceived to influence study participation, treatment acceptability and 
adherence; risk taking behavior; and treatment preferences. By emphasizing the social and physical context 
of participant’s lives and their understandings of health, interviews are intended to provide insight into the 
ways in which these contexts shape treatment adherence and possible reinfection. The following constructs 
are constructs and sample themes that will guide in-depth interviews. 
Level 
Factors 
Topics/Theme 
Individual 
Self-worth 
Please tell me about experiences when you’ve been 
denied HCV treatment in the past? 
Do you feel that you deserve to be treated for HCV? 
What does having access to HCV treatment mean to 
you?  
Do you think that people who use drugs deserve 
treatment? 


Page 14 of 20 
 
Perceived 
treatment 
selfefficacy 
Do you think you will be able to take the treatment as 
prescribed? What factors do you think will make it 
challenging for you? 
 
Risk Behaviors 
What is your understanding of safer injection practices?  
What risk behaviors do you think put you at risk for 
Hep C (ex. Needle sharing, sharing cocaine straws, 
etc)? How often did you/do you use safer practices (eg.  
Needle exchange).  
Household 
Sexual Partner 
How has your sexual partner shown to be supportive of 
your health? How has your sexual partner made it more 
difficult for you to be healthy? How does your sexual 
partner feel about your participation in this study? 
 
Family 
How has your family shown to be supportive of your 
health? How has your sexual partner made it more 
difficult for you to be healthy? How does your family 
feel about your participation in this study? 
 
Household 
resources 
Income/financial resources/housing stability/work and 
migration/household size/access to health care 
 
Life Events 
Birth, deaths/funerals, employment changes/changes in 
relationships 
Organizational Clinical sites 
Perception of hospitals; perception of CBOs; comparing 
perception of context of study sites 
 
Group  
Participation in support groups 
 
membership  
 
 
Social services 
Access to other services in relation to HCV treatment 
(e.g., housing, recovery, ORT, needle exchange) 
Community 
HCV  
perceptions 
HCV acceptances/stigma; experiences of discrimination; 
What do people in your community think about HCV?  
 
Community 
resources 
Access to health and other social services, public 
transportation; CBOs 
 
Cultural Norms 
Practices around pill/medication taking, cultural beliefs 
about doctors and medical providers (e.g., trust, 
conspiracy theories) 
 
Information flow 
and beliefs 
Rumors/beliefs about clinical studies, HCV 
transmission, HCV treatment 
 
Influence of institutional belief systems (e.g., churches, 
recovery fellowship) 
 
Informal and formal social and community networks 
(e.g., drug use networks) 


Page 15 of 20 
7. 
Data and Specimens a. Handling of Data and Specimens 
All data will be collected by the primary provider, site principle investigators, or site coordinators. 
This data will be disassociated with personal identifiers, re-associated with a nondescript study ID, 
and uploaded into OHSU-sanctioned confidential data management service such as RED Cap, on a 
daily basis.  
We will collect basic demographical information, including age, gender, ethnicity, substance abuse 
disorder/drug of choice and current use status, and housing status. The primary outcome measured 
will be SVR at 24 weeks (12 weeks post-treatment). Secondary outcomes include adherence (% pills 
missed, per fill and total), relapse or ongoing injection drug use at 48 weeks, and re-infection or 
treatment failure at 48 weeks.  
Data storage will be for a period of 5 years or less, unless formal permission requested of the OHSU 
IRB for extension. Subjects will be consented for indefinite data storage. 
Please see uploaded data collection and consent forms. 
 
b. Sharing of Results with Subjects 
All personal, clinical information will be shared with subjects in accordance of the standard of care. This 
includes lab values (done at CLIA certified laboratories Quest and Labcorps), imaging results, and other 
aspects of routine hepatitis C treatment. Results of secondary measures, including survey data and 
indepth interviews, will not be shared directly with subjects. Subjects will be able to access the final 
publication(s) upon request.   
 
c. Data and Specimen Banking 
Subjects will be assigned a study ID on paper and data will be entered into an encrypted/password 
protected excel spreadsheet by the site principle investigator or study coordinator. The study ID will not 
contain any of the 18 HIPPA identifiers and will be available only to the PIs and IRB approved study 
collaborators. This document will be maintained, password protected, in the RED Cap repository. At 
each visit, a subject’s study ID will be accessed from the Master List and a de-identified, study ID-linked 
opaque envelope with data sheets for all 10 visits will be pulled from a secure location. All non-clinical 
care data will be initially collected on paper by the data collector, provider, or study coordinator and 
then entered into de-identified data sets in the RED Cap repository by the study coordinator on a weekly 
basis. The paper copy will be replaced into the opaque envelope and then confirmed by a separate, IRB 
approved study volunteer. Standard of care clinical data will be entered in the electronic medical record 
and endpoints pre-specified in this protocol will be transferred to the RED Cap repository by the study 
coordinator on a weekly basis. When the study is fully enrolled and all participants complete the 48week 
visit, or are lost to follow up, the paper datasets will be destroyed in medical recycling facilities at each 
site. 
In the retrospective OHSU cohort, all data will be entered immediately into RED Cap and then confirmed 
by a separate investigator at the OHSU site.  
As part of the primary consent document, all participants will legally consent by written signature to 
storage of non-biological study data in a secure repository for future investigations. No biological 
specimens of any type will be stored beyond what is needed to complete laboratory tests at the point of 
care. For instance, blood will be drawn and sent to the clinical laboratory (LabCorp, Quest Diagnostics) 


Page 16 of 20 
and stored ONLY for the purposes of performing the lab, in concordance with standard practices. In 
most cases this will not exceed a week and never more than two weeks. No genetic testing will be 
performed as a part of this study and thus none will be shared. All electronic data will be maintained 
encrypted in the RED Cap repository. Only the primary investigator, Atif Zaman, and two coinvestigators, 
Ryan Hutchison and Andrew Seaman, will have access to these data following study termination. These 
data will be maintained separate from personal identifiers, and only the PI and coinvestigators will have 
access to the master spreadsheet linking study ID and personal identifiers. These personal identifiers will 
not be made available to external researchers at any time, and so no personally identifiable information 
will be shared with external researchers. Andrew Seaman, co-investigator and primary study contact, 
will be listed as the repository guardian. If contacted for use of study data for any purpose, he will be 
responsible for ensuring data are released according to OHSU policy and the IRB approved repository 
protocol, executing a repository sharing agreement in case data are released for future research, 
ensuring the security and confidentiality of all stored data, ensuring the security and confidentiality of 
data during transfer, and tracking acquisitions and releases of data. He will also maintain access to the 
master spreadsheet linking study ID to personal identifiers, in order to identify data sets for which 
consent has been withdrawn and ensuring no future use.  
After study completion, any future release of data collected will be contingent upon the repository 
guardian verifying a separate full IRB approval for each specific human subject research activity that uses 
identifiable repository data. The repository guardian will be personally responsible for verifying that 
future releases of data are done in concordance with pre-proposed limits and the original consent. Data 
transport at the time of any potential future IRB approved data sharing will be clarified and approved at 
the time of data by submission of an updated Repository Sharing Agreement and separate IRB approval. 
Any updated data requests and Repository Sharing Agreements will be stored alongside study data in 
the Red Cap repository in a separate file entitled “Repository Sharing Agreements and External Data 
Requests.” This will be maintained and tracked by Andrew Seaman. External researchers will be required 
to use the Red Cap repository for all data storage, therefore data transfer will not be necessary and data 
security ensured.  
No data submittal from outside sources is expected.  
8. Data Analysis 
1) For primary endpoint: descriptive analysis and chi-squared test for comparative analysis 
2) For secondary endpoints:  
• 
Descriptive analysis 
• 
Explore bivariate and multivariate associations between psychosocial factors computed through 
scales (e.g., stigma, social support, quality of life) and (a) treatment readiness at baseline, (b) 
treatment outcomes [SRV, biological outcomes, etc.] at 12 months, (c) re-infection (or SRV) at 48 
months. Demographic controls will include age, education, work status, and relationship status. 
• 
Conduct constant comparative qualitative analysis of focus group and individual discussions using 
Atlas.ti software. The domains of analysis will include lived experiences with stigma, discrimination, 
positive and negative social support systems, and risk management. Emergent themes and domains 
identified through qualitative analysis will result in a richer understanding of factors that contribute 
to implementing successful treatment for people who currently use drugs. 


Page 17 of 20 
In addition to the above, mixed methods data will comprise biological data, psychosocial data collected 
via questionnaires, and qualitative narrative data from transcribed in-depth interviews.  
Using Dedoose software, the research team will work together to systematically analyze the data in the 
following steps: 1) exploratory within-case analysis; 2) descriptive across-case analysis; 3) analytic 
within-case analysis; and 4) analytic across-case analysis—each “case” being an individual included in 
the study.  
The overall goal is to draw connections among the domains laid out in the socio-ecological conceptual 
framework, exploring patterns that indicate how social and institutional experiences may shape 
vulnerability to HCV and success in treatment outcomes. This type of reflexive analysis is crucial when 
performing real-world clinical research that takes into account psychosocial factors and social context.  
Exploratory within-case analysis involves reading interviews and marking sections with compelling 
and/or representative stories, quotes, or instructive idioms. Noteworthy aspects of each case are 
summarized, contributing to the development of a preliminary set of codes. Rather than deciding a 
priori the taxonomies for sorting individuals, themes and codes emerge from the data itself. 
Descriptive Across-Case Analysis involves generating descriptions of key domains articulated in the 
socio-ecological conceptual framework. This across-case analysis will describe the range within each 
domain, articulating—for example—the range of participants’ experiences interacting with medical 
institutions, trust in medication, experiences of stigma related to HCV or drug use, subject social 
network’s views of medical treatment, as well as institutional elements of receiving care at community 
clinic settings with multiple social services.  
For the analytic within-case analysis, the team will develop and test explanations of how the institutional 
and social contexts of people’s lives shape their treatment outcomes. This includes adherence to 
treatment, SVR, and vulnerability to HCV reinfection. This involves pooling interview, biological and 
psychosocial data to describe frequencies and relationships between key domains and outcomes. This 
analytic within-case analysis will correct for any theoretical oversights in the conceptual framework and 
may generate new analytic codes. 
Analytic across-case analysis entails comparative analysis, distinguishing between groups of people who 
exhibit different behavioral patterns. This allows the investigators to go beyond simple assertions about 
majority and minority patterns and to make analytic—as opposed to descriptive—statements about 
how certain values or behaviors relate to broader psychosocial and institutional factors. 
Power/Sample Size: 
Based upon a sample size of n=50 subjects in the combined safety net/needle exchange clinics and 50 
subjects in the retrospective comparator group, this study has 80% power to detect a 20% difference 
between groups; this calculation is based on the assumption that the retrospective comparator group 
will have and SVR12 rate of 95% (taking into account treatment discontinuation and relapse rates, i.e. 
intention to treat analysis) compared to SVR12 rate of 70% in the safety net clinic patients.  
In the intervention group (safety net clinics) a total of 50 subjects will be enrolled to allow for a 10% 
attrition and loss to follow up. 


Page 18 of 20 
9. Privacy, Confidentiality, and Data Security 
All data will be collected and entered in a private, clinical care environment, behind closed doors. All 
study collaborators with access to personal data, de-identified or not, will be required to undergo full 
OHSU IRB training.  
At Old Town Clinic, subjects will be recruited as described in Section 5e. There will be limited risk of a 
privacy violation with this method. The consent process will be performed during the course of a clinical 
visit, in an exam room, one-on-one with the site coordinator.  
At Outside In, subjectss will be recruited as described in Section 5e. There will be limited risk of a privacy 
violation with this method.  The consent process will be performed after a clinical visit in a private office 
in the syringe exchange, one-on-one with the site coordinator. 
At all sites, laboratory and/or imaging tests, clinical visits, dispensation of medications, and 
communication of test results will be performed in concordance with HIPPA appropriate clinical care. All 
surveys and qualitative data will be collected in a private space, such as an exam room or meeting room 
behind closed door. 
For more details, please see section 7c above.  
10. Provisions to Monitor the Data to Ensure the Safety of Subjects 
See DSMP document, attached.  
9. 
Risks and Benefits a. 
Risks to Subjects 
• 
Surveys and Questionnaires. Some of the questions in the questionnaires or 
interviews have the potential to be re-traumatizing. All study personnel have 
training in trauma informed care and know how to minimize this risk. Subjects have  
the right to refuse to answer any questions.  
• 
Lab Tests and Images. There is minimal risk of discomfort associated with lab draws.  
• 
Treatment. About 1/100 people experience a temporary increase in their serum 
transaminase, ALT, to about 5 times the upper limit of normal. This typically resolves 
after completion of treatment. In previous studies, about 1/10 patients experienced 
headaches and fatigue during treatment. However, this is about equivalent to, or 
only slightly higher than, placebo in most studies. In one study, patients on 
ZepatierTM were slightly more likely to have nausea than patients on the placebo. 
ZepatierTM can interact with some other medications, these will be screened for by 
study pharmacists and clinicians prior to drug initiation.10 
 
b. Potential Benefits to Subjects 
ZepatierTM, and other direct acting antiviral agents targeting hepatitis C, are extraordinarily 
effective at eradicating the disease, between 92 and 97%10. The morbidity of hepatitis C is 
described well above. Patients with lower fibrosis scores are being denied access to treatment 
by insurance companies in this and other states due to cost concerns, despite this being contrary 


Page 19 of 20 
to national guidelines. Patients are also frequently denied for having a substance abuse disorder, 
even though the majority of new infections in the United States occur in this population. As 
such, we know very little about the treatment of hepatitis C in active or recent PWIJs.  
Subjects who participate in this study will have free access to a highly effective, FDA approved 
treatment for hepatitis that will likely cure their disease. They will also have access to intensive, 
wrap around services they would not likely enjoy at a referral center where they would typically 
get treated. The ancillary data collected in surveys and interviews may help individualize therapy 
options, including prescribing frequency, etc., and will contribute to the body of knowledge to help 
better care for their community.  
10. Drugs or Devices (delete if not applicable) 
Open label drug supplies will be required by Merck.   
Our institution's pharmacy will require packed and labeled medication containers in English.    
At conclusion of the study or upon drug expiration, the Merck GRS will be responsible for issuing a Drug 
Disposition Letter to the investigator for US based studies.   
The investigator will be responsible for the destruction of the supplies at the study center pursuant to the 
ICH/GCP Guidelines, local regulations and the investigator’s institutional policies. Clinical supplies must 
be received by a designated person at the study site, handled and stored safely and properly, and kept in 
a secured location to which only the investigator and designated assistants have access. Clinical supplies 
are dispensed in accordance with the protocol. The investigator is responsible for keeping accurate 
records of the clinical supplies, the amount dispensed to and returned by the subjects, and the disposition 
at the end of the study. 
Zepatier is FDA approved and well tolerated. The prescriber information is included in study documents.  
11. References 
1) Bruggmann P, Litwin AH. Models of care for the management of hepatitis C virus among people who 
inject drugs: one size does not fit all. Clin Infect Dis. 2013;57 Suppl 2:S56-S61. 
2) Islam MM, Topp L, Conigrave KM, et al. Linkage into specialist hepatitis C treatment services of injecting 
drug users attending a needle syringe program-based primary healthcare centre. J Subst Abuse Treat. 
2012;43(4):440-445. 
3) Aspinall EJ, Corson S, Doyle JS, et al. Treatment of hepatitis C virus infection among people who are 
actively injecting drugs: a systematic review and meta-analysis. Clin Infect Dis. 2013;57(Suppl 2):S80-S89. 
Education and peer support sessions references modeled after previously validated peer support groups for 
treatment with interferon-based regimens 
4) Sylvestre DL, Litwin AH, Clements BJ, Gourevitch MN. The impact of barriers to hepatitis C virus 
treatment in recovering heroin users maintained on methadone. J Subst Abuse Treat 2005; 29:159–165. 


Page 20 of 20 
5) Grebely et al. Optimizing assessment and treatment for hepatitis C virus infection in illicit drug users: a 
novel model incorporating multidisciplinary care and peer support. European Journal of 
Gastroenterology & Hepatology 2010, 22:270–277. 
Questionnaire instruments based on the following references where the scales were used, validated with HCV 
treatment clients. 
Addiction Scale: 
6) AI Newman, S Beckstead, D Beking, et al. Treatment of chronic hepatitis C infection among current and 
former injection drug users within a multidisciplinary treatment model at a community health centre.  
Can J Gastroenterol 2013;27(4):217-223. 
Both MOS Social Support and Addiction Scale: 
7) Mason, K et al. (2015) Beyond viral response: A prospective evaluation of a community-based, 
multidisciplinary, peer-driven model of HCV treatment and support, International Journal of Drug Policy 
26:1007–1013 
Constant Comparison Analysis Method: 
8) Glaser, Barney G. "The constant comparative method of qualitative analysis." Social problems 12.4 
(1965): 436-445. 
Capacity:  
9) Grisso T, Appelbaum PS. Abilities related to competence. In: Assessing competence to consent to 
treatment A guide for physicians and other health professionals, Oxford University Press, New York 
1998. p.31 
Zepatier Complications: 
10) 1) ZepatierTM Prescriber Information, Merck & Co.  
https://www.merck.com/product/usa/pi_circulars/z/zepatier/zepatier_pi.pdf. Accessed 8/20/2016. 

ICF_001.pdf: 
 
 
 
Page 1 of 2 
 
 
IRB#: __16357_ 
 
 
 
Project Title:  
Hepatitis C Treatment in PWIDs: MAT or Syringe Exchange Assisted-therapy vs 
Standard of Care 
 
NCT Number: 
NCT03093415 
 
Last Review/Edits: 
January 20, 2019 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
Page 2 of 2 
Research Consent Summary 
 
You are being asked to join a research study. You do not have to join the study. Even if you 
decide to join now, you can change your mind later. 
 
Some parts of the study are optional. You may participate in the main study without 
participating in the optional parts. 
 
1. 
The purpose of this study is to learn more effective ways to treat people living with 
both hepatitis C and a substance abuse disorder.  
2. 
We hope that we can show that:  
a. by asking participants about their experience with addiction and hepatitis c, they 
can teach us new and innovative ways to treat this terrible virus.   
b. we can treat hepatitis C in participants suffering from substance abuse in the 
safety net clinic setting as, or more effectively as referring to specialty treatment 
center.  
c. a substance abuse disorder diagnosis should not prevent access to treatment of 
hepatitis C.  
d. the risk of hepatitis C reinfection in people who inject drugs is low under 
appropriate medical care. 
3. 
Merck & Co., Inc. is paying for the research study. 
4. 
Everyone who joins the study will participate in surveys and in depth interviews. 
Participants will be provided with the FDA approved hepatitis C treatment, ZepetierTM 
(known as “the study drug” in the rest of this form), and all screening labs, at no charge.  
5. 
If you join the study, you will have ten visits over 18 months, and you will be taking 
medicine for 12 weeks of this time. We will also ask you to fill out surveys and participate 
in one or more interviews during the initial visits to help us better understand how to 
support you through treatment and improve the care of our participants with hepatitis C.  
6. 
Your medical record will be reviewed and collected for your medical diagnoses, blood 
tests and imaging study results, and liver biopsy and/or FibroScan result.   
7. 
Some of the survey and interview questions may seem personal and may upset you. 
You may refuse to answer any of the questions that you do not wish to answer. There is 
minimal risk of breach of confidentiality 
8. 
The in-depth personal interviews are optional. You may decide not to participate in these 
portions if you do not wish to. You will be asked separate permission prior to any of the 
optional portions of the study. 
9. 
If you agree to participate in this study, the information collected may be stored, 
separate from your personal identifiers, for an indefinite period of time for future 
research, including possible evaluation for risk of repeat infection. Use of your study 
information for future study is optional.  
 
 
 


 
 
 
Page 1 of 7 
 
 
 
 
IRB#: __16357___ 
 
 
 
 
Research Consent and Authorization Form 
 
TITLE:  A prospective cohort study comparing the effectiveness of Zepatier for the treatment of 
hepatitis C in an academic center population to people who inject drugs (PWIDs) in a 
safeteny net clinic setting engaged in either Medication Assisted Therapy or syringe 
exchange program. 
 
PRINCIPAL INVESTIGATOR: 
Dr. Atif Zaman, 503-494-8071 
    Co-Investigators: 
                                                                 Dr. Andrew Seaman, 971-271-6102 
Dr. Ryan Hutchinson, 503-535-3800  
 
 
FUNDED BY: Merck & Co. 
 
SUPPORTED BY: OHSU, Central City Concern, and Outside In Clinic 
 
CONFLICT OF INTEREST: The primary investigators currently have no conflicts of interest.  
The lead primary investigator will not receive any compensation for this study.  
The co-investigators will receive a total of 5% of their salaries from the research grant  
from Merck & Co. 
 
PURPOSE: 
You have been invited to be in this research study because you have hepatitis C virus (HCV) 
infection, wish to proceed with treatment but are unable to access it due to current insurance 
restrictions. The purpose of this study is to learn more effective ways to treat people living with 
both hepatitis C and a substance abuse disorder, in the community setting.  
 
This study will be conducted at Old Town Clinic and Outside In; both are safety net clinics in the 
downtown Portland area. Approximately 25 people will be enrolled at each of these sites.  
 
There will be a total of 50 participants in this part of the study. The study will require 10 clinic 
visits over 18 months.  
 
We are asking you to provide information for a data bank, also called a repository.  This 
information will be stored indefinitely and may be used and disclosed in the future for research. 
 
 


 
 
 
Page 2 of 7 
PROCEDURES: 
1) Surveys. You will be asked to complete a total of three separate surveys. You will take these 
surveys during your first visit in the program and again in the last encounter. We expect 
these surveys to take between 15 and 25 minutes.  
 
2) Interview (optional). We may also invite you to be interviewed at any of these time points; 
this portion of the study is optional. You will be asked questions about your social support, how 
you feel about your hepatitis C, some basic information about your background (such as your 
age and ethnicity, for example), and what ideas you have about what we can do to make your 
treatment most successful. This optional portion of the study will take between 60 and 90 
minutes, for which you will be compensated. Your medical record at your current primary care 
office, Old Town Clinic or Outside In, will be reviewed and collected for your medical 
diagnoses, blood tests and imaging study results, and liver biopsy and/or FibroScan result. 
 
We do not plan to share the results of surveys and interviews with you, though the published 
results of the study can be made available to you on request. If we discover information that 
is important for your health care, either in this study or in the future, we will contact you and 
ask if you want to know the results. You may learn information about your health that is 
upsetting. 
 
3) Lab Tests and Imaging. If your primary care provider or clinic hepatitis C provider feels it 
is indicated, you will be asked to have labs drawn to help them better treat your hepatitis C. 
You may also be asked to do a liver test called a fibroscan, which uses an ultrasound to see 
how much damage the hepatitis C has caused to your liver. These results will be shared with 
you as it is a part of your normal medical care. 
 
4) Treatment. If you enter the study and meet national guidelines for treatment of your 
hepatitis C, the study drug will be started at the recommended dose for a total of 12 weeks.  
 
RISKS AND DISCOMFORTS: 
1) 
Surveys and Interviews. Some of the questions in the surveys or interviews may seem 
personal or embarrassing. They may upset you. You may refuse to answer any of the 
questions that you do not wish to answer. If the questions make you very upset, we will help 
you to find a counselor. 
2) 
Lab Tests and Images. We will draw blood from a vein in your arm.  You may feel some 
pain when your blood is drawn.  There is a small chance the needle will cause bleeding, a 
bruise, an infection, or fainting. Some participants with a history of injection drug use may find 
the needles involved triggering. The fibroscan imaging is not thought to cause discomfort and is 
without known health risks. 
3) 
Treatment. About 1/100 people experience a temporary increase in their liver test called 
ALT to about 5 times the upper limit of normal. This typically resolves when you finish 
treatment. In previous studies, about 1/10 participants experienced headaches and fatigue 
during treatment. However, this is about the same number of participants with headache and 
fatigue that received a false pill called placebo, and so these side effects may not have been 
caused by the drug. In one study, participants on the study drug were slightly more likely to 
have nausea than participants on the placebo (false pill). The study drug can interact with some 
other medications. Your provider and pharmacist will look for all these interactions and make 
adjustments as necessary and as agreed upon by you.  
 
 


 
 
 
Page 3 of 7 
 
BENEFITS: 
You may or may not personally benefit from being in this study. .  However, by serving as a 
subject, you may help us learn how to benefit patients in the future. 
 
 
ALTERNATIVES: 
You may choose not to be in this study. 
 
CONFIDENTIALITY: 
We will take steps to keep your personal information confidential, but we cannot guarantee total 
privacy. Confidentiality will be protected by (a) assigning you a code number, (b) identifying 
surveys and interview transcript by code number and not name, (c) changing any identifiable 
information in the transcripts with synonyms and (d) storing the data obtained from completed 
surveys, transcripts, medical record reviews, and demographic data on a secure computer with 
a restricted password. 
 
We will create and collect health information about you as described in the Purpose and 
Procedures sections of this form. Health information is private and is protected under federal law 
and Oregon law. By agreeing to be in this study, you are giving permission (also called 
authorization) for us to use and disclose your health information as described in this form. 
 
The investigators, study staff, and others at OHSU may use the information we collect and 
create about you in order to conduct and oversee this research study and store in a repository, 
and conduct future research. The storage in a repository and future use of your information is 
optional. The stored data will be without identifiers and only released as requested. 
 
We may release this information to others outside of OHSU who are involved in conducting or 
overseeing research, including: 
 
o The funder of this study, Merck and Co.  
o The Office for Human Research Protections, a federal agency that 
oversees research involving humans. 
 
Those listed above may also be permitted to review and copy your records. 
 
We will not release information about you to others not listed above, unless required or 
permitted by law.  We will not use your name or your identity for publication or publicity 
purposes, unless we have your special permission. 
 
The law provides additional confidentiality protection for certain types of information, 
including drug and alcohol addiction, treatment, or referral information, as well as mental 
health records. We will collect basic information regarding your active or former substance 
use. We may disclose this information, separated from patient identifiers, until the study 
has ended. This will enable us to better understand how to treat you for your hepatitis C, as 
well as treat people in the future who also suffer from substance abuse disorders. We may 
access this information in the future to investigate risk of re-infection of hepatitis C due to 
resumption of risk behavior, such as injection with used needles. 
 
When we send information outside of OHSU, they may no longer be protected under federal 
or Oregon law.  In this case, your information could be used and re-released without your 


 
 
 
Page 4 of 7 
permission. 
 
Data from this study may be shared with other investigators for future research studies. All 
identifying information about you will be removed from the data before they are released to 
any other investigators. 
 
We may continue to use and disclose your information as described above indefinitely. 
 
Some of the information collected and created in this study may be placed in your medical 
record.  While the research is in progress, you may or may not have access to this 
information.  After the study is complete, you will be able to access any study information 
that was added to your medical record.  If you have questions about what study information 
you will be able to access, and when, ask the investigator. 
 
COMMERCIAL DEVELOPMENT:  
Samples and information about you or obtained from you in this research may be used for 
commercial purposes, such as making a discovery that could, in the future, be patented or 
licensed to a company, which could result in a possible financial benefit to that company, 
OHSU, and its researchers.  There are no plans to pay you if this happens.  You will not 
have any property rights or ownership or financial interest in or arising from products or 
data that may result from your participation in this study.  Further, you will have no 
responsibility or liability for any use that may be made of your samples or information. 
 
COSTS: 
Some of the services or items in this study are part of the regular treatment for your 
condition. These would be performed or used even if you were not in this study.  The costs 
for these services or items will be billed to your insurance. You will be responsible for any 
costs your insurance does not cover. If you have any questions about these costs, or what 
out-of-pocket expenses you may be responsible for, contact your insurance company.  
   
 
You will be compensated for all components of the study felt to be outside the scope of routine 
medical care. This includes two separate survey sessions and one in-depth interview session.  
For each of these sessions you will be compensated with one $15 Fred Meyer Gift Card.  
 
 
LIABILITY: 
If you believe you have been injured or harmed as a result of participating in this research 
and require treatment, contact Dr. Atif Zaman at 503-494-8071. 
 
If you are injured or harmed by the study procedures you will be treated. OHSU, Outside In, Old 
Town Clinic, and the funder do not offer any financial compensation or payment for the cost of 
treatment if you are injured or harmed as a result of participating in this research. Therefore, any 
medical treatment you need may be billed to you or your insurance. However, you are not 
prevented from seeking to collect compensation for injury related to negligence on the part of 
those involved in the research. Oregon law (Oregon Tort Claims Act (ORS 30.260 through 
30.300)) may limit the dollar amount that you may recover from OHSU or its caregivers and 
researchers for a claim relating to care or research at OHSU, and the time you have to bring a 
claim. 
 
If you have questions on this subject, please call the OHSU Research Integrity Office at (503) 


 
 
 
Page 5 of 7 
494-7887. 
 
PARTICIPATION: 
If you have any questions, concerns, or complaints regarding this study now or in the future, 
contact Dr. Atif Zaman at 503-494-8071, Old Town Clinic co-Investigator Andrew Seaman at 
(971) 271.6102, or Outside In co-Investigator at 503-535-3800. 
 
This research is being overseen by an Institutional Review Board (“IRB”). You may talk to the 
IRB at (503) 494-7887 or irb@ohsu.edu if: 
• 
¥ Your questions, concerns, or complaints are not being answered by the research 
team. 
• 
¥ You want to talk to someone besides the research team. 
• 
¥ You have questions about your rights as a research subject. 
• 
¥ You want to get more information or provide input about this research. 
 
You may also submit a report to the OHSU Integrity Hotline online at  
https://secure.ethicspoint.com/domain/media/en/gui/18915/index.html or by calling toll-free (877) 
733-8313 (anonymous and available 24 hours a day, 7 days a week). 
 
Your participation in this study is voluntary. You do not have to join this or any research 
study. You do not have to allow the use and disclosure of your health information in the study, 
but if you do not, you cannot be in the study.  Some parts of the study are optional.  You can 
choose not to participate in some or all of the optional parts but still participate in the rest of 
the study. 
 
If you do join the study and later change your mind, you have the right to quit at any time. 
This includes the right to withdraw your authorization to use and disclose your health 
information. Talk to the investigator if you want to withdraw from the study.  You can choose 
to withdraw from some or all of the optional parts of this study without withdrawing from the 
whole study. If you choose not to join any or all parts of this study, or if you withdraw early 
from any or all parts of the study, there will be no penalty or loss of benefits to which you are 
otherwise entitled, including being able to receive health care services or insurance 
coverage for services. Talk to the investigator if you want to withdraw from the study or 
change which parts of the study you are participating in. 
 
If you choose to withdraw from the study, we will ask you to participate in one additional 
visit with your provider to ensure you get the best possible treatment of your condition. At 
that time, we will destroy all the information collected during the study, including the paper 
and electronic versions. Your information will not be available for future research.  
 
 
If you no longer want your health information to be used and disclosed as described in this form, 
you must send a written request or email stating that you are revoking your authorization to: 
 
Attention: Dr. Andrew Seaman, Hepatitis C Study Coordinator, 727 W Burnside, Portland, OR, 
97209. 971-271-6103 / seaman@ohsu.edu 
 
Your request will be effective as of the date we receive it. However, health information 
collected before your request is received may continue to be used and disclosed to the 
extent that we have already acted based on your authorization. 
 


 
 
 
Page 6 of 7 
You may be removed from the study if the investigator stops the study. 
We will give you any new information during the course of this research study that might 
change the way you feel about being in the study. 
 
 
The information that we will collect from you will be stored separately from your name or any 
other identifier. We will be able to use this information to destroy your information should you 
chose to withdraw from study at any time in the future. Only three doctors, Dr. Zaman at OHSU, 
Dr. Seaman at Old Town Clinic, and Dr. Hutchison at Outside In will have access to personally 
identifiable information. If you choose to allow your information to be used for future research, 
this information will only be made available separate from your name or personal identifiers. 
 
 
 
 
 
 
 
 
PARTICIPANT OPTIONS 
 
The optional portions of this study are described in detail throughout this consent form 
and listed here as a summary. Please read the options and place your initials next to your 
choices. You can still participate in the main part of the study even if you choose not to 
participate in the optional parts. 
 
 
_____ I give my consent to participate in the optional interview portion of the study and 
will  
            accept the compensation of a $15 Fred Meyer gift card for doing so. 
 
_____  I give my consent for my information to be stored for future research.  
 
 
 
 
 
 
 
SIGNATURES: 
 
Your signature below indicates that you have read this entire form and that you agree to be in 
this study. 
 
We will give you a copy of this signed form. 
 
 
 
_________________         _______________________      ___________ 
  
  
 
Subject Printed Name                      Subject Signature                                      Date 
 


 
 
 
Page 7 of 7 
 
________________________             ________________________________         _______________ 
 Person Obtaining Consent,              Consenter Signature                                 Date 
Printed Name