Oregon HIV/Hepatitis and Opioid Prevention and Engagement (OR-HOPE) Study: Tele-HCV Treatment Trial
Phase: NA
Conditions: Hepatitis C
Sponsor: Oregon Health and Science University

Page 1 of 17 
 
 
 
 
 
 
 
 
 
Protocol Title: Oregon HIV/Hepatitis and Opioid Prevention and 
Engagement (OR-HOPE) Study: Tele-HCV Treatment Trial 
 
 
 
 
 
Principal Investigator:  
P. Todd Korthuis, MD 
 
 
 
 
OHSU 
 
 
 
 
(503) 494-8044 
 
ClinicalTrials.gov ID:  
NCT04798521 
 
 
 
Protocol Revision Date: 
October 13, 2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Page 2 of 17 
 
 
 
 
 
Oregon HIV/Hepatitis and Opioid Prevention and Engagement (OR-
HOPE) Study: Tele-HCV Treatment Trial 
 
Principal Investigator:  
 
P. Todd Korthuis, MD 
 
 
 
 
 
 
OHSU 
 
 
 
 
 
 
(503) 494-8044 
 
 
ClinicalTrials.gov ID:  
 
NCT04798521 
 
  
 
 Protocol Revision Date: 
 10/13/2022 
 
 
 
Objective 
 
The main goal of this study is to test the efficacy of a peer-facilitated telemedicine HCV treatment 
implementation strategy for people who use drugs versus local HCV treatment referral for achieving 
HCV sustained viral response at 12 weeks post-treatment (SVR12). 
 
 Background 
 
Untreated drug use is associated with increased hepatitis C (HCV) risk. People living in rural areas – with 
limited access to prevention and treatment resources – may be particularly susceptible to unchecked 
HCV transmission. A recent analysis identified six rural county characteristics associated with acute HCV 
infection rates - mainly due to injection drug use - including drug-overdose deaths, prescription opioid 
sales, per capita income, white non-Hispanic race/ethnicity, unemployment, and limited buprenorphine 
prescribing capacity.  
 
 
HCV transmission is primarily driven by injection drug use. As a result, HCV is endemic among 
people who used drugs (PWUD). Guidelines state that HCV treatment should be prioritized among 
patients with substance use disorders, yet only a small percentage (<10%) of PWUD access treatment. 
The advent of newer highly effective, direct-acting anti-HCV treatments provides an opportunity to limit 
or even eradicate HCV. However, realizing treatment benefits depends on whether PWUD can be 
identified, tested, and linked to care, and many PWUD in rural communities struggle to engage with 
traditional health settings and testing mechanisms. In particular, venipuncture based diagnostics can be 
traumatizing and challenging for people with current or past injection drug use. Several studies held 
outside of the United States have suggested improved test acceptance with dried blood spot (DBS) 
versus traditional venipuncture by as much as four fold and test operating characteristics where 
acceptable. These tests have not yet been validated for use in the United States with commercial 
laboratories. For this purpose, we will implement the study in two phases. Phase 1; validating the DBS 
testing measures, Phase 2; implementing telemedicine hepatitis C treatment after DBS diagnosis. 
Continuing to phase 2 will not be contingent on phase 1.  
 
 
New systems of care delivery that integrate HCV treatment in rural areas are urgently needed. 
Telehealth interventions, which directly connect patients to remote treatment providers, are a potential 
solution which may support HCV treatment uptake in rural areas. Peer support specialists are people 
with lived experience in recovery who reach, engage, and retain hard-to-reach populations. They utilize 
their past shared experiences drug use and recovery to develop rapport and link patients to care. Peer 
support specialists can facilitate HCV testing and linkage to telehealth HCV treatment for people who 
use drugs. 

Page 3 of 17 
 
 
 
  
Study Design Non-blinded, randomized controlled trial. In-depth qualitative interviews assess 
attitudes and barriers to treatment.  
 
The study will be implemented in two phases; Phase 2 is not contingent on Phase 1.  
 
 
Study Population 
a) Number of Subjects 
In Phase 1, potential participants will be pulled from a convenience sample at a Portland clinic providing 
care for the urban area. An initial target sample of 100 Hepatitis C positive participants will be enrolled 
for DBS validation. Power will be reassessed based on feedback from receiver operating curve model 
and additional participants enrolled up to a total of 100 Hepatitis C Positive participants, if necessary. A 
total of 500 potential participants can be screened expecting 1 in every 4 participants will be positive 
HCV. 
 
In Phase 2, rural peer care coordinators (PCCs) and research assistants recruit up to 200 PWUD 
participants from high-needs rural Oregon counties. Study staff specifically target untreated 
populations recruited from local syringe exchange programs and direct community outreach (e.g. 
community barbeques, parks, homeless shelters, food pantries, etc.). Participants are 
encouraged to refer others for study screening. 
 
A subset of up to 40 study participants will complete in-depth qualitative interviews regarding their 
experiences of hepatitis C treatment. 
 
Inclusion and Exclusion Criteria 
 
Phase 1: Initial DBS Validation Aim 
Participants are eligible for inclusion if they: 
1) present in person to Central City Concern (CCC) health services for other critical needs 
2) elect to screen for hepatitis C, HIV, and hepatitis B while waiting for other health service 
completion  
3) are age 18 years or greater 
 
Participants are excluded if they: 
1) inability to perform consent, DBS testing, or incentive distribution without increasing participant 
social exposure or personal protective equipment utilization 
actively receiving HCV treatment 
 
Phase 2: TeleHepC Aim 
Participants are eligible for inclusion if they: 
1) live in the study area 
2) have injected drugs or report recreational opioid use without injection in the last 90 days 
3) are age 18 or greater 
4) have chronic active, untreated hepatitis C (defined as positive HCV RNA) 
5) are seeking treatment for hepatitis C infection. 
6) are able to communicate in English (this is due to the fact that less than 5% of the population in 
which we are targeting will be non-English speaking; see “Non-English Speaking Subjects” for 
additional information). 
7) are enrolled in health insurance 

Page 4 of 17 
 
 
 
Participants are excluded if they: 
1) Have decompensated cirrhosis, defined as Child-Turcotte-Pugh (CTP) score of 7 or greater, 
or CTP B cirrhosis. CTP scoring is a composite of laboratory metrics (bilirubin, albumin, 
PT/INR) and clinical findings, including:  
a. increased abdominal or lower extremity swelling  
b. confusion consistent with hepatic encephalopathy 
2) Are pregnant or breastfeeding 
 
b) Vulnerable Populations 
Children:  Children will not be included in the study; subjects age 18 and greater are eligible for inclusion.   
 
Prisoners: This study is likely to enroll persons involved in the criminal justice system related to 
substance use. The study will not recruit persons incarcerated/detained in a correctional facility or 
currently considered “prisoners” by local or state laws, but will not exclude parolees or probationers. 
Those participants who become incarcerated during the course of their involvement with this study will 
continue to be followed to ensure safety and data integrity. If necessary, specific documents for 
incarcerated participants will be developed and approved by the OHSU IRB. Appropriate progress notes 
will be written to ensure complete documentation of any interaction with an incarcerated participant, 
specifically mentioning confidentiality procedures.  
 
The project has been granted a federal Certificate of Confidentiality. An OHRP Prisoner Research 
Certification Letter will be filed through the OHSU IRB and distributed to the sites. Local sites will be 
covered by both OHSU’s Certificate of Confidentiality and the OHRP Prisoner Certification to enable 
study follow up visits for participant who may become incarcerated.    
 
c) Non-English Speaking Subjects 
Oregon opioid use disorder demographics suggest the Oregon Hispanic/Latino population has been 
relatively spared from this epidemic. Hispanic/Latino patients accounted for 3.7% of opioid use disorder 
treatment admissions in the North Coast and Southwest Oregon grant target regions in 2015, and nearly 
all speak English. We consequently anticipate a very small fraction of study participants will be mono-
lingual Spanish speaking. The very small numbers provide insufficient statistical power to assess 
differences by language group. We thus believe that collecting Spanish language data is not justified on 
scientific grounds for this study. 
 
Setting 
Participating Sites: 
1 Oregon Health & Science University (OHSU) leads the project, under the direction of Dr. Korthuis. 
OHSU will participate in data quality assurance during study implementation analysis, train PCCs 
and research assistants (RAs) in study procedures, conduct analyses, and disseminate qualitative 
and quantitative results. HIV Alliance and Comagine are deferring to OHSU’s IRB; the Oregon 
Health Authority will be using its own IRB for project review. 
 
2 HIV Alliance is a community based service organization providing support for HIV and HCV 
treatment and prevention and syringe exchange services in rural Oregon counties. HIV Alliance 
outreach workers will serve as intervention PCCs. HIV Alliance PCCs will recruit and provide linkage 
to care for PWUD, and an HIV Alliance research assistant staff will support HIV Alliance syringe 
exchange staff in collecting survey and laboratory data. 
 
3. Bay Area First Step (BAFS) is a community based service organization that provides housing, and 
peer-delivered services designed to support individuals and families. BAFS peer mentors will serve 
as intervention PSSs. BAFS PSSs will recruit and provide linkage to care for PWUD and collect 
survey data.  BAFS plays an active role in the community and has strong relationships with potential 
participants. 

Page 5 of 17 
 
 
 
 
4.  Comagine conducts qualitative focus groups and interviews and lead the qualitative analysis.  
 
5. Oregon Health Authority investigators will assist in administrative support of tele-HCV treatment 
and advise the study team on implementation, interpretation, and dissemination of study findings. 
 
6. Implementation Locations: The study catchment area includes Douglas, rural Lane, Josephine, 
Coos, Curry, Tillamook, Umatilla, and Clatsop counties.  
 
7. Central City Concern: CCC is a community-based homelessness services organization located in 
Portland, Oregon. They will participate as the Phase 1 site for DBS validation. CCC hepatitis C 
team staff will perform usual HCV screening and linkage-to-care interventions, consent individuals 
for DBS validation study inclusion, perform DBS testing, and deliver and track incentives. 
 
8.  Oregon Washington Health Network (OWHN) is a community-based network that addresses 
mental and physical health, and houses peer support specialists.  Peer support specialists will 
recruit participants and facilitate telemedicine appointments.  The OWHN research assistant will 
consent participants and conduct study assessments.    
 
d) Recruitment Methods 
 
Participant Recruitment:  
Phase 1: Central City Concern continues to screen for and treat hepatitis C during the COVID-
19 pandemic providing clients are presenting in-person for other critical health services. 
Individuals are offered HCV screening by clinic intake and HCV team staff. CCC clients on 
campus who opt-in to screen for hepatitis C will be offered venipuncture screening and 
confirmation labs as per usual clinical practice. After assent to testing, individuals will offer 
optional participation in DBS validation study.  
 
Participants will receive $30 upon completion of DBS test.  
 
Phase 2:  HIV Alliance already supports syringe exchange and rapid HIV/HCV screening in Douglas, 
Lane, Josephine and Coos Counties. Community-based syringe exchange programs will serve as initial 
recruitment sites and supplemented with community settings (e.g. parks, homeless shelters, community 
barbeques, etc.). Research staff will also approach participants of the Oregon HOPE study who have 
previously consented to be contacted for future research and offer them study participation. Our 
preliminary data suggest that HCV treatment is highly sought-after by PWUD in intervention counties. 
 
This project will use snowball sampling to recruit participants. Research staff will encourage 
participants to use their personal networks to invite individuals who may be interested in partaking in 
the intervention. There will not be incentives provided for referrals or a specific set number of 
participants encouraged to recruit.  
 
Compensation: Participants will receive compensation in the form of cash if they are located in 
Douglas, Josephine, Coos, Curry or Josephine County. OWHN participants will receive compensation 
in the form of Visa gift cards.   
 
In the event a participant becomes incarcerated, with their permission, the study team may 
give their study compensation to a friend or family member to pass along to them so they may 
have access to it while incarcerated. If the participant does not give permission, compensation 
will be given to participant when they are able to receive it. 

Page 6 of 17 
 
 
 
 
Activity 
Cash or gift card Incentive Amount 
Prescreen/ Rapid Test/ Blood Draw/ Dried Blood 
Spot Testing, Full Consent 
 $20 
Screening blood draw 
$20 
*If necessary* second blood draw for missed 
blood draws 
$20 
Return for Results and Baseline Survey 
$15 
4 - Week survey 
$20 
End of treatment survey  
$30 
*12-weeks after end of treatment survey 
$20 
*12-weeks after end of treatment blood draw 
$40 
36 weeks after end of treatment survey, 
reinfection labs 
$30 
Total 
$215 
 
Cash Incentives:  
Tracking systems will be handling cash compensation. The RA will document the serial number of each 
bill upon obtaining the cash and again when distributing cash to the participant. Research staff will 
internally audit and count cash incentive records each week. The Quality Assurance staff member will 
audit monthly. When carrying cash in the field, only small, pre-counted amounts of cash will be carrier. 
These will be kept in a locked box in a discrete location of the vehicle.  
 
Study participants may choose to seek substance use treatment at residential treatment facilities.  
Some residential facilities discourage or prohibit patients from having cash at the facility while in 
treatment. When a study participant is a patient of such a facility and continues to engage in study visits 
and activities, field staff will hold their study incentives in a locked box at the study office, and distribute 
funds to the participant when they leave residential treatment. 
 
Gift Card Incentives:  
Tracking systems will be handling electronic gift cards. The RA will document the gift card number upon 
distribution. Research staff will internally audit the gift card count.   The electronic gift card tracking 
sheet will be kept in a secure folder on Box 
 
e) Consent Process 
 
Phase 1: 
Potential participants will be consented by IRB-approved CCC HCV team staff at the time of usual care. 
Extreme efforts will be made to ensure potential participants are able to maintain social distancing 
precautions before, during, and after the engagement with the HCV team. Consent will be offered at the 
time of testing in a private room one on one with HCV team staff using existing COVID-19 protocol 
screening practices, consisting of N95 mask and face shield for staff and surgical mask for participants. 
All surfaces, pens used for consent, and high touch surfaces will be sterilized as per CCC practices. Staff 
will remind consenting participants that participation is voluntary and that they may withdraw their consent 
at any time. Participants will be assessed for understanding of study procedures. 
 
Phase 2: 
 
People who use drugs will be consented by IRB-approved research assistants, Peer Care Coordinators 
or syringe exchange outreach staff employed by HIV Alliance who have completed human subjects 
training. The consent process will take place in a private area with only the participant and the Peer Care 
Coordinator or syringe exchange outreach staff present. In cases where PWUD are consented in 

Page 7 of 17 
 
 
 
community-based settings (e.g. parks, etc.), research staff and peers will make sure they are out of 
hearing distance of others for consent and data collection. Peer care coordinators or syringe exchange 
outreach staff will remind consenting participants that participation is voluntary and that they may 
withdraw their consent at any time. Participants will be assessed for understanding of study procedures.  
 
 
 
Procedures 
 
Phase 1 Procedures:  
Prescreening Procedures:  
Participants presenting for standard of care HCV, HIV, and HBV screening will consent to Phase 1 of 
the study using a full consent form. This includes consent for:  
• 
Blood draw for hepatitis C RNA and hepatitis B core Antibody 
• 
Dried Blood Spot card testing procedure (RA or self-administered)  
• 
Blood samples to be shipped to an external lab 
 
 
All labs will be reviewed by the study clinicians except for the DBS card and serum lab specimens 
collected for DBS validation, which will not be used for clinical decision making. The serum lab 
specimens collected for DBS validation will only be sent to Molecular Testing Laboratories for the 
purpose of DBS card validation and results will not be relayed to the participant. 
 
Chart abstraction will be performed in order to collect basic demographic information.  Past lab test 
results will also be abstracted in order for comparisons to be performed.   
 
Phase 2 Procedures:  
 
Pre-Screening Procedures: 
 
The HCV rapid test will be optional. If participants self report a positive HCV test previously, they can 
enroll in the study by self-disclosure of +HCV. If their HCV status is unknown, a rapid test will be 
performed. If a positive rapid test in the past is reported, an optional rapid test can be completed as part 
of the study. People who test negative have the option to retest at 6 months. It is anticipated that a 
significant number of potential participants will screen negative for HCV. If a participant opts to have the 
HCV rapid test done, a positive result is an eligibility requirement for the study.  Participants will be 
asked to sign  a full consent form to indicate consent for rapid HCV testing, Inclusion/Exclusion check-
list, and Locator Form completion—as well as the screening phase, randomization, and treatment arm 
interventions.  Upon consent, establishment of baseline known positivity and treatment experience, 
peers or RAs will perform point of care HCV rapid antibody testing (OraQuick® HCV Rapid Antibody 
Test). (See figure 1: Telemedicine Study Flow Diagram). The HCV Rapid Antibody Test is a finger prick 
that can either be administered by study staff or self-administered, depending on participant and/or staff 
preference  If it is decided that a self-administered test will be performed, participant will be given an 
instruction sheet on how to administer the test.  Study staff will be present to answer questions and 
ensure the procedures are correctly followed. Study staff will assist participant in registering for 
Medicaid Accountable Care Organization (ACO), if needed and applicable.   
 
Upon positive rapid HepC test, participants will be moved to the screening phase. Those with a 
negative rapid HepC test are not eligible for the study.  
 
Peers and/or RAs will assist participants with reactive tests to go to a community laboratory for 
completion of one of four screening algorithms based on past treatment experience (see figures 2, 3) 
 

Page 8 of 17 
 
 
 
Screening Procedures: 
 
Participants with a positive HCV RNA will be accompanied to the lab for a serum lab draw and 
confirmatory lab draw ordered by the study clinician. Due to the health conditions that many participants 
are experiencing (dehydration, collapsed veins, etc.), it is likely that participants will need to return for a 
second confirmatory lab draw.  Additional compensation will be provided if a second blood draw is 
needed.  Research staff review screening survey and lab tests are entered into Child-Turcot-Pugh 
(CTP) calculator. Only participants with a CTP score of 6 or platelets < 150,000mm3 will be referred for 
study clinician evaluation to confirm treatment eligibility; who will be blinded to treatment allocation until 
eligibility determined. All others will be fully screened by research assistant in the community. Once 
enrollment is confirmed, all participants will complete baseline surveys and randomization and then 
continue with treatment arm interventions as per Figure 1. 
 
Central City Concern ONLY: 
Participants with reactive antibody tests will also be offered participation in the hepatitis C and hepatitis 
B core antibody dried blood spot validation study, which would include performing a point of care dried 
blood spot test and completing confirmation serum HCV PCR and hepatitis B surface antibody testing. 
DBS specimens will be collected by peers and/or RAs and serum for confirmation by community 
partner laboratories. The DBS card will be shipped to Molecular Testing Laboratories for testing. 
 
Allocation:  
 
Participants are randomized using a centralized random number assignment for treatment allocation 
developed at OHSU and assigned through RedCap.  
 
Intervention Design:  
Central City Concern ONLY:  Phase 1: Once in-house potential participants are identified they will be 
offered participation in the DBS study by IRB-trained CCC HCV team staff. Participants will provide a 
phlebotomy-derived blood sample and finger stick capillary blood sample for DBS card. These will be 
sent to MTL for DBS validation using standard human biohazard sample laboratory storage and 
shipping techniques consistent with MTL procedures. Incentives will be dispensed at the time of DBS 
sample collection or along with critical medications or services already provided, whichever method 
entails less on campus time for participants. 
 
Phase 2:  
Participants are randomized to peer-facilitated telehealth-HCV treatment intervention versus referral to 
local HCV treatment providers to initiate HCV treatment. After labs confirm preliminary eligibility, 
randomization will be generated by REDCap after baseline and consent.  Participants with a CTP of 6 
will connect with a study clinician over WebX to confirm eligibility. The participant is withdrawn if the 
study clinician deems ineligible. Local HCV treatment referral providers have treated at least one 
patient with HCV previously. They are encouraged to participate in the OHSU HCV ECHO tele-
mentoring sessions, but are not study participants. 
 
Study Arm 1: Tele-HCV Treatment Arm Procedures: 
 
Participants allocated to telemedicine intervention arm are scheduled for treatment assessment by a 
study clinician. For a majority of participants, this will also be the treatment initiation visit. If additional 
studies are necessary for routine treatment decision making, peers will assist participants in navigating 
health system barriers and arrangement of second telemedicine visit. The telemedicine study clinician 
will perform a standard of care hepatitis C treatment initiation history and submit a prescription for 
DAAs. Prior authorizations will be completed by study clinician pharmacist.  
  

Page 9 of 17 
 
 
 
All patients initiating treatment will be prescribed HCV medication treatment for 4 weeks at a time. The 
majority of patients will require two separate dispensations at week 0 and week 4 for a total of 8 weeks 
of medications, with a small subset requiring third, 4-week dispensation for a total of 12 weeks of 
therapy. The study clinical pharmacist will check in with the participant by telephone or telemedicine 
visit at week 0, week 4, and end of treatment to 1) determine general medication tolerance, 2) assess 
quality of adherence and 3) dispense medications by mail or ensure medications received, depending 
on participant’s insurance. Peers will assist participants in keeping telehealth appointments and 
navigating medication pick up or storage, if not mailed directly to the home. Participants who report new 
onset of jaundice or other signs of hepatic decompensation during participation will be scheduled for a 
follow up telemedicine visit with a physician by the research assistant, receive repeat laboratory studies 
if needed, and if necessary, be referred to local providers for ongoing medical care. If problems or side 
effects arise during treatment, participants will call the research assistant, who will connect them to a 
study clinician.  
 
HCV labs will be repeated at 12 weeks post end of treatment and results will be relayed to the 
participant in the SVR12 follow up visit with the research assistant, along with follow up surveys. Those 
successfully achieving SVR12 will be counseled on ongoing harm reduction methods. Those showing 
persistent HCV viremia at 12 weeks post treatment will be referred to community-based HCV treatment 
providers for treatment re-initiation. All will be scheduled for 36 week post end of treatment survey visit.  
 
SVR12 labs will be collected 12 weeks post-treatment in community partner labs. Dried Blood Spot 
specimens will be once again collected at this point by research assistants at the point of SVR12 
survey data collection.  
 
Telehealth visits will be performed via the chosen web platform of the participant. This includes but is 
not limited to: Facebook, Facetime, Skype, Zoom, Webex, WeChat, etc. The treatment initiation visit, 
pharmacist adherence assessments, and SVR12 lab communication will all be documented in the 
electronic medical record using PHI and no study identifiers.  
 
Study Arm 2: Community Linkage-To Care Arm (Control Condition) Procedures: 
 
Participants allocated to the community linkage-to-care arm will complete screening, be offered 
enrollment, and undergo informed consent as in the telemedicine arm. Following study inclusion and 
enrollment, research staff will refer the participant to a local community health clinic to engage in 
hepatitis C care and seek treatment. Peers will assist patients to engage with local primary care and 
health plan resources and will receive an information sheet on optional clinics to attend and questions 
to ask their provider. TAU participants will be encouraged to take this to their visit.  Research assistants 
will outreach to participants regularly to determine if they have engaged in local health resources and 
schedule assessment visits. A bidirectional release of information will be requested. The study clinical 
pharmacist or research assistant will assess adherence medication adherence at week 4 and end of 
treatment via telephone. SVR12 laboratory testing will be performed by the community provider with at 
least one telephone reminder prior to lab due date. 12 weeks post end of treatment study assessments 
will coincide with SVR12 lab results visit and 36 week post end of treatment assessments performed as 
in the telemedicine arm.  
 
Chart abstraction for participants in both arms will be performed in order to assess the number of and 
types of interactions the peers have with participants.   
 
In either arm, participants who do not initiate treatment by 12 weeks after randomization will begin their 
assessment timeline, mirroring treatment timeline for an 8-week direct acting antiviral regimen. For 
these participants, the study research assistant will collect study assessments at week 16 
(corresponding to 4-week post-treatment initiation), week 20-22 (corresponding to end of treatment 
visit), week 32 (corresponding to 12 weeks post-treatment visit), and week 56 (corresponding to 36 

Page 10 of 17 
 
 
 
weeks post-treatment visit) after randomization; the primary study outcome will be assessed at 32 
weeks after randomization. 
  
Participant Assessments: 
 
Phase 1:  
• 
Blood draw and DBS specimen collection for HCV RNA and Hepatitis B core antibody 
 
Phase 2:  
 
Assessment/Activity 
Pre-
Screen Screen Baseline 
(Week 0) 
4-Week 
after 
treatment 
initiation 
End of 
Treatment 
12-week 
Post-
Treatment 
***36-Week 
Post 
Treatment 
Completion 
As 
Needed 
Pre-Screening Survey 
X 
  
  
  
  
 
  
  
Demographics 
 
 X 
  
  
  
 
  
  
Inclusion/Exclusion 
 
X 
  
  
  
 
  
  
Rapid HCV Test 
X 
  
  
  
  
 
  
  
CPT Assessment 
 
 X 
  
  
  
 
  
  
Participant Survey 
 
 
 
 
 
 
 
 
Medical Care History 
  
  
X 
  
 X 
X 
***X  
  
Barriers to treatment 
  
  
X 
  
 X 
x 
***x  
  
Engagement with 
Harm Reduction & 
Substance Use 
Treatment 
  
  
X 
X 
X 
X 
 ***X 
  
Substance Use 
  
  
X 
X 
X 
X 
 ***X 
  
Perceived Stigma of 
Drug Use 
  
  
X 
X 
X 
X 
 ***X 
  
HCV Treatment 
History 
  
  
X 
  
 X 
 
  
  
HCV Treatment 
Completion 
  
  
  
  
X 
 
  
  
HCV Treatment 
Adherence 
  
  
  
X 
X 
 
  
  
Treatment 
Satisfaction 
  
  
  
  
X 
 
 
  
Experience with 
Telemedicine 
  
  
  
  
**X 
 
 
  
Experience with Peer 
Support Specialist 
  
  
  
  
 **X 
 
  
  
Blood Draw/ Medical 
Procedures 
  
  
  
  
  
 
  
  
HCV RNA 
  
X 
  
  
 
X 
  
  
Hepatitis B Sag 
  
X 
  
  
 
 
  
  
Hepatitis B SAg 
  
X 
  
  
 
 
  
  
Hepatitis B cAb 
  
X 
  
  
 
  
  
  
Hepatitis A Ab 
  
X 
  
  
 
 
  
  
CMP 
  
X 
  
  
 
X 
  
  

Page 11 of 17 
 
 
 
CBC 
  
X 
  
  
 
X 
  
  
INR/prothrombin 
 
X 
 
 
 
 
 
 
HCV genotype  
 
X 
 
 
 
 
 
 
B-HCG (women<50) 
  
X 
  
  
 
 
  
  
SC Reviews Labs 
  
X 
  
  
 
X 
  
  
Ultrasound 
  
  
  
  
  
 
  
**X 
Telemedicine Visit 
  
  
**X 
  
  
 
  
  
Medication 
Counseling 
  
  
**X 
**X 
X* 
 
  
  
HCV Genotype and 
Resistance Testing 
  
  
  
  
  
 
  
**X 
Chart Abstraction 
 
 
 
 
X 
X 
 
 
Peer interaction log 
 
 
 
 
X 
 
 
 
HCV treatment 
provider visits 
 
 
 
 
X 
 
 
 
Administrative 
  
  
  
  
  
 
  
  
Written informed 
consent 
 
X 
 
 
 
 
 
 
Locator Form 
x 
 
X 
X 
X 
X 
 
X 
Master Enrollment 
Log 
 
 
X 
 
 
 
 
 
Progress Note Check 
List 
X 
X 
X 
X 
X 
X 
X 
  
Reportable Events 
Log 
  
  
  
  
  
 
  
X 
Adverse Event 
  
  
  
  
  
 
  
X 
Inventory Form 
  
  
  
  
  
 
  
X 
Visit Compensation 
Log 
X 
  
X 
X 
X 
X 
X 
  
***X: 36 Week Survey only if participant qualifies  
**X: Only Telemedicine Pt.   
 
 
 
*X: Number of weeks of treatment depends on ppt.   
 
 
 
 
 
Participants complete brief REDCap surveys regarding symptoms, substance use, and harm reduction 
engagement at baseline, 4 weeks, end of treatment, 12 post end of treatment, and 36 weeks post end 
of treatment. These surveys will be conducted over the phone or in person.  
 
Participants undergo phlebotomy at screening and 12 post end of treatment. 
 
Study Measures: 
The primary outcome is sustained viral response at 12 weeks post treatment (SVR12). Secondary 
outcomes include a) HCV treatment initiation, b) HCV Treatment completion (filled final prescription and 
self-reported > 90% HCV treatment pills taken), c) engagement with harm reduction resources, d) 
substance use, e) perceived stigma, and f) engagement in addiction treatment resources. Exploratory 
endpoints include a) treatment satisfaction with hepatitis C treatment, adapted from the single-item 
Medication Satisfaction Questionnaire, and b) reinfection vs. virologic relapse/failure. 
 

Page 12 of 17 
 
 
 
Adherence to Phone Visits: Adherence to these phone visits is defined as +/- 5 days 
 
Prescreen, baseline and follow-up surveys collected in the field or via phone will first be documented on 
paper forms. These will then be entered into REDCap by the RA. The source documents will be kept in 
a locked file cabinet in a secure location.  
 
Qualitative interviews will be recorded on an encrypted recorder and stored on a secure, encrypted 
computer.  
 
Survey data will be used to determine HCV status of participants with a detectable plasma HCV RNA, 
which were collected on or after SVR12 timepoint (either 12 weeks after end of treatment for those who 
initiated treatment or 32 weeks after randomization for those who did not initiate treatment). The 
primary SVR12 outcome will be sustained viral response 12 weeks after treatment for participants who 
initiated treatment within 6 months. Participants who did not start treatment within 6 months will be 
considered treatment failure. Measuring detectable plasma HCV RNA for both participants who initiated 
and did not initiated within 6 months of randomization will provide a framework to assess for potential 
biasing impact of spontaneous clearance on assumption of treatment failure for participants who did not 
initiate treatment within 6 months. 
 
Probable Relapse/Failure: Probable virologic relapse or failure is defined as a detectable plasma HCV 
RNA 12 weeks or more after the end of treatment if a) participant denies any injection drug use, or b) 
participant injecting drugs but notes 100% adherence to recommendations on Safe injection practices, 
including use of clean works (cooker, cotton, rinse) with every injection. 
 
Probable Reinfection: Probable reinfection is defined as a detectable plasma HCV RNA 12 weeks or 
more after the end of treatment if a) participant completes full course of DAA regimen, and b) 
participant notes injection behavior of substantial risk, including i) Receptive use of injection equipment 
(needles, cotton, cooker) from someone of either unknown HCV serostatus or known positive 
serostatus on one or more occasion and ii) use happened between end of treatment and HCV RNA test 
 
Indeterminant Relapse vs Reinfection: Indeterminant virologic relapse vs reinfection is defined as a 
participant with a detectable plasma HCV RNA 12 weeks or more after the end of treatment in 
participants a) not completing DAA regimen, and b) with injection behavior of substantial risk, as noted 
above. 
 
Qualitative Interview Procedures: 
We will conduct qualitative interviews by telephone with a sample of purposively selected study 
participants. An interview guide will be used, and interviews will last approximately 45 minutes. Up to 35 
interviews will be conducted by trained researchers. Participants will be reimbursed $50 for their 
participation. The participant qualitative interview guide will assess tele-HCV acceptability, satisfaction, 
perceived quality of care, advantages and disadvantages relative to face-to-face appointments, and 
barriers and facilitators to treatment initiation and adherence. Questions will also examine the role of 
peers in facilitating telemedicine, medication access, and adherence. 
 
We will also conduct virtual focus groups with peer support specialists and tele-HCV clinicians. The 
peer support specialist focus group guide will assess tele-HCV and HCV treatment barriers and 
facilitators; peer specialist activities and adaptations; and advantages and disadvantages of tele-HCV. 
The clinician focus group guide will assess peer-assisted tele-HCV procedures; barriers and facilitators; 
experiences engaging with specialty pharmacies, payers, and peers; and clinical considerations related 
to tele-HCV. 
   
 

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Data and Specimens 
a) Handling of Data and Specimens 
 
Survey Data: Participants complete brief surveys regarding symptoms and substance use at baseline, 
4, end of treatment, 12 weeks post-end of treatment, and 36 weeks post end of treatment. Survey data 
will be collected from PWUD by Research staff or PCCs, via 2-in-1 laptops or local office PCs or hand-
held devices using REDCap data collection, detailed below (Privacy, Confidentiality, and Data Security).  
 
Biologic Specimen Data:  Biological specimen data will be stored at Peace Health, Mercy Medical, and 
Molecular Testing Labs. Serum samples drawn for DBS validation will be completed at Peace Health and 
Mercy Medical and shipped to Molecular Testing Labs.  
 
Participant Locator Form Data: We will collect identifying information (name, social security number, 
date of birth, address, phone numbers, employer information, e-mail address, and other contact 
information) to use for follow-up of patient for future studies. The locator form also asks what forms of 
social media are commonly used and where the individual commonly spends most of their time. 
Participants will be contacted on social media using a highly-private account specific to the study. Index 
after the study is completed. Data will be collected on paper and the original will stored in a locked file 
cabinet at HIV Alliance for the duration of the study. Data will be abstracted into a spreadsheet in Box, 
maintained behind the OHSU firewall, for future use. Only HIV Alliance and OHSU will have access to 
this information. 
 
b) Sharing of Results with Subjects 
Results of HCV tests will be shared with the participant.   
 
c) Data and Specimen Banking 
De-identified specimens may be shared with other researchers, including the National Rural Opioids 
Initiative data coordinating center at University of Washington, Molecular Testing Labs, and other 
National Rural Opioids Initiative collaborators. This study does not include genetic research. Participant 
contact information (including name, date of birth, address, and Social Security Number) will be entered 
by study staff into a spreadsheet in OHSU BOX and stored behind the OHSU firewall. Participants who 
indicate willingness to be contacted for future studies in the consent form may be contacted and offered 
participation in future studies. Dr. Korthuis will serve as the guardian of this repository.  Dr. Korthuis will 
ensure that data is received and released according to OHSU policy and the IRB approved repository 
protocol.  A repository sharing agreement will be executed each time data is released for research 
purposes.  Dr. Korthuis will track all releases of data.  Should a participant withdraw their consent, Dr. 
Korthuis will indicate this in an additional spreadsheet that will be kept in OHSU BOX, and will ensure 
that the participant’s data is destroyed.  Participants from OR-HOPE indicate in the informed consent 
form whether or not they agree to future contact regarding participation in additional studies.   
 
To certify documentation of local IRB approval to the OHSU IRB, a copy of the approval letter from the 
contributing site will be included in the submission to the repository.  Consent to contact for future studies 
and to store data will be obtained from the participant when the participant signs the optional section of 
the informed consent form.  To document whether the person from whom the data was obtained signed 
a legally effective consent and authorization, study staff will review the signatures and date from the 
original consent form and indicate the date that it was signed in the data collection spreadsheet.   
 
To ensure security and confidentiality during the collection of data, only study staff will be entering data 
into the data collection spreadsheet in OHSU BOX.  Only OHSU’s PI and Research Assistant and HIV 
Alliance study staff will have access to the data in OHSU BOX.  Only Dr. Korthuis will be able to grant 
access to the BOX files.  A Certificate of Confidentiality will be obtained to further protect the sensitive 
information obtained from participants.   
 

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Data Analysis:  
 
Pre-specified analyses for this study will be intention-to-treat (ITT) comparisons between telemedicine 
and treatment as usual (local treatment referral) on primary and secondary outcomes. Prior to 
conducting these analyses, we will compare baseline covariate distributions (demographics, etc.) 
between randomized groups using standardized mean differences (SMDs) and bivariate statistical tests 
(e.g. t-tests, Chi-square tests). If a significant imbalance in any variable is noted, i.e., a SMD > 0.25 and 
p < .2, we will include that variable as a covariate in future analyses. All primary and secondary 
analyses will utilize generalized linear (mixed) models (GLMMs) with distributions and link functions 
appropriate for the distribution of the outcome variable. Fixed effects of interest in the models will be 
timepoint (baseline, 4 weeks, end of treatment, 12 weeks post-treatment, 36 weeks post-treatment), 
randomized group (telemedicine vs. TAU), and their interaction. If more than one timepoint is included 
in the analysis, GLMMs will include person-level random intercepts to account for repeated 
measurements on subjects. Hypotheses will be tested using between-group comparisons at each 
timepoint of interest, or within-group comparisons across timepoints.  
 
Hypothesis 1: Participants randomized to receive tele-HCV treatment will have superior SVR-12 rates 
compared to those randomized to TAU (referral for local treatment).  
 
Analytic strategy: We assess the effect of telemedicine versus TAU on SVR at 12 weeks post-
treatment completion using logistic regression. Missing HCV viral load data will be considered non-
suppressed in the main ITT analysis. Sensitivity analyses will include a per-protocol analysis and a 
repeat of the main analysis using multiple imputation of missing data.  
 
Hypothesis 2: Participants randomized to receive tele-HCV treatment will have superior rates of HCV 
treatment initiation (filled first prescription) compared to those randomized to TAU.  
 
Analytic strategy: We assess the effect of telemedicine versus TAU on treatment initiation by 4 
weeks post-baseline using logistic regression. Missing treatment initiation data will be considered non-
initiated in the main ITT analysis. Sensitivity analyses will include a per-protocol analysis and a repeat 
of the main analysis using multiple imputation of missing data. 
 
Hypothesis 3: Participants randomized to receive tele-HCV treatment will have superior rates of HCV 
treatment completion (filled final prescription and self-reported > 90% HCV treatment pills taken) 
compared to those randomized to TAU.  
 
Analytic strategy: We assess the effect of telemedicine versus TAU on treatment completion by 12 
weeks post-baseline using logistic regression. Missing treatment completion data will be considered 
incomplete in the main ITT analysis. Sensitivity analyses will include a per-protocol analysis and a 
repeat of the main analysis using multiple imputation of missing data.  
 
Hypothesis 4: Participants randomized to receive tele-HCV treatment will have a higher likelihood of 
engagement with harm reduction resources, lower rates of substance use, lower stigma, and higher 
engagement in addiction treatment resources compared to those randomized to TAU (referral for local 
treatment).  
 
Analytic strategy: We assess the effect of telemedicine versus TAU on these outcomes at all post-
baseline timepoints using mixed effects regression models. Missing outcome data will be handled using 
full information maximum likelihood. We will conduct per-protocol analyses as sensitivity analyses.  
 
Qualitative Evaluation. Audio-recorded interviews will be professionally transcribed; transcripts will be 
uploaded into qualitative analysis software (NVivo). Comagine research staff create a coding scheme, 
conduct coding, and revise in an iterative process that has been successfully implemented by the study 
team in other mixed-methods projects. The qualitative data provides complementary information to 
illuminate and expand quantitative findings, including survey results and measures of treatment 
initiation and completion. 

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Privacy, Confidentiality and Data Security 
Our study procedures reflect high levels of protection for subjects.   
 
Training will include time for direct communication of specific roles.  HIV Alliance oversees PCC hiring, 
support, and intervention implementation at in participating counties. Study site visits will be a critical 
aspect of study success. OHSU research staff will visit PCC field sites at least quarterly support 
implementation and review data collection.  
 
Data will be stored in a manner intended to preserve patient confidentiality. Consent forms and all 
PHI will be stored in locked cabinets and on password protected, secure computers.  Only study team 
members will have access to data on secured computers. Participant hard-copy survey data will be 
stored only at study sites in a locked cabinet until study conclusion. Survey data will be identified only 
with a unique randomly generated identifier. The identifier will be used instead of subject names or 
medical record numbers and will not contain any part of the 18 HIPAA identifiers. The file linking the 
unique identifier with the patient’s name will be stored in a separate password-protected file on a 
secure computer at study sites. Only the study site and overall Study Coordinator, and OHSU PI 
(Todd Korthuis) will have access to the linked file. Survey data will be entered in the secure OHSU 
REDCap system by study staff, and study team members. Site and OHSU study staff will have access 
to the de-identified data in REDCap.  No identifiable information will be emailed between 
investigators.  Data are coded before any transfer.  De-identified data may be shared following data 
lock with the national rural opioids initiative data coordinating center at University of Washington. 
 
Survey data will be collected using OHSU’s instance of REDCap. Access to the database will be limited 
to OHSU IRB-approved study staff that are approved to contact or interact with participants. REDCap 
is a secure, customizable, web-based application for building and managing databases (see 
https://octri.ohsu.edu/redcap/index.php). REDCap resides on a server housed in ITG's Advanced 
Computing Center (ACC) and is maintained by developers in the Oregon Clinical and Translational 
Research Institute (OCTRI) in accordance with all relevant OHSU policies and guidelines. 
Additionally, ACC employs a second firewall within the OHSU network to attain a high level of security 
and access control. In situations when a secure WiFi connection is not available for REDCap data 
collection, REDCap Mobile App will be used as an offline data collection means until a WiFi 
connection is available to securely transmit data to the main REDCap database. REDCap Mobile App 
database is encrypted on the mobile device’s hard drive using SQLCipher to prevent someone from 
breaking into the file in the event of a stolen device. The REDCap Mobile App will be used on an 
encrypted laptop/tablet purchased through ITG. REDCap Mobile App with reviewed and approved by 
ITG Security Engineering group prior to implementation. As a back-up, we may need to collect data 
using paper surveys and then entering data into REDCap when an internet connection becomes 
available. If paper surveys are used, those files will be held in a locked case, and stored in locked 
cabinet in a locked office to securely handle these data.   
 
Qualitative Data.  Interviews will be digitally audio-recorded and professionally transcribed and 
transcripts will be uploaded into qualitative analysis software (NVivo) by Comagine study team 
members. Recordings will be destroyed following analysis. Qualitative interview data will be stored at 
Comagine on secure servers in password-protected files, accessible only to researchers and subject 
to Comagine’s policy on safeguarding electronic data. Study documents and audio recordings will not 
contain any identifiable information, but instead will be assigned a unique study identifier. The list 
linking participants to their unique identifier will be password-protected and maintained within the 
study’s secure REDCap database. 
   
All study personnel will complete on-line training in appropriate conduct of research through the 
OHSU IRB, or equivalent training. The Institutional Review Board of Oregon Health & Science 
University has policies in place that meet the requirements of 45 CFR 46, Subpart C. The Board 

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reviews all protocols that involve prisoners; does not permit waivers of consent for subjects who are 
prisoners; requires OHRP certification once IRB approval is granted; and includes a prisoner 
representative on the Board during consideration of prison-related proposals, continuing reviews, and 
amendments. The research protocol will also adhere to the federal policies for protection for children 
involved as subjects in research (45 CFR 46, Subpart D). The proposed research complies with the 
Additional Protocol Requirements of 45 CFR 46, Subpart A. The research will be on a condition 
(substance use disorder) that particularly affects children age 13-21. 
 
 
Risks and Benefits  
a) Risks to Subjects 
 
Risk of Underlying Conditions: As the study population will have significant ongoing health and 
substance use issues, events related to complications of HCV and substance use may occur, including 
admission for substance use detoxification and treatment, hospitalizations for medical and psychological 
complications, and death. These events will be captured on study specific forms. 
 
Risks to Confidentiality: There are also risks to confidentiality, particularly because we collect 
information about substance use. There is also a risk to confidentiality when using telehealth due to the 
internet and Wi-Fi use.  
 
Phlebotomy Risks: Blood drawing for confirmatory testing may cause pain or bruising at the site and 
carries a small risk of infection. 
 
Telemedicine Risks: Telemedicine participants may be less likely to engage in other primary care 
services than peer-assisted primary care intervention arm.  
 
b) Potential Benefits to Subjects 
Subjects may benefit from participation in the proposed study by being diagnosed with HCV and offered 
assistance in enrolling with health insurance, and harm reduction services during screening. 
Subjects who are diagnosed with hepatitis C may also benefit by gaining access to treatment and 
cure in a region with little current treatment access.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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