Hepatitis C Treatment in PWIDs: MAT or Syringe Exchange Assisted-therapy vs Standard of Care

Study Overview
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Brief Summary
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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
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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.

Official Title
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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 Safety Net Clinic Setting Engaged in Either a Medication Assisted Therapy (MAT) or Syringe Exchange Program

Conditions
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Hepatitis C, Substance Use Disorders, Substance Abuse, Intravenous

Intervention / Treatment
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* Drug: elbasvir-grazoprevir (50 mg/100 mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Genotype 1b and genotype 1a without baseline NS5A resistance or Genotype 4 APRI Score <0.7; if >0.7 a Fibrosure/Fibrotest or Fibroscan score of F2 or less No clinical or laboratory evidence of cirrhosis Readiness for treatment based on ability to make >2/3 sequential office visits Patients must be assessed to have decision-making capacity, be capable of consenting, and not be displaying evidence of overt intoxication. Exclusion Criteria: Clinical or Laboratory Evidence of Cirrhosis Elevated prothrombin time unrelated to anticoagulation, hemoglobin level less than 12.3 g/L in females and <14 g/L in males, platelet count <150 × 109 cells/L), white blood cells (WBC) <4.0 x103/mm3 , aminotransferase levels more than 10 times the upper limit of normal, or albumin level <3.5 g/L. Previous treatment for hepatitis C infection Hepatocellular carcinoma HIV or hepatitis B virus co-infection Subjects taking medications that are contra-indicated to administer with Zepatier including phenytoin, carbamazepine, rifampin, St. John's Wort, and cyclosporine AND unable to change these medications to one without interactions.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two parallel investigational groups in different community health clinic treatment settings assigned to treatment with elbasvir-grazoprevir as compared to an academic hepatology clinic retrospective cohort treated with elbasvir-grazoprevir.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Old Town Clinic, Medication Assisted Therapy group<br>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. | Drug: elbasvir-grazoprevir (50 mg/100 mg)<br>* 12 week treatment of elbasvir-grazoprevir (50 mg/100 mg)<br>* Other names: Zepatier;|
| Active Comparator: Outside In Clinic, Needle Exchange Program<br>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. | Drug: elbasvir-grazoprevir (50 mg/100 mg)<br>* 12 week treatment of elbasvir-grazoprevir (50 mg/100 mg)<br>* Other names: Zepatier;|
| Other: OHSU Hepatology Clinic, Academic center Retrospective Cohort<br>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. | Drug: elbasvir-grazoprevir (50 mg/100 mg)<br>* 12 week treatment of elbasvir-grazoprevir (50 mg/100 mg)<br>* Other names: Zepatier;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR 12 | Sustained Viremic Response at 12 weeks post-completion of treatment. SVR12 was determined negative if undetectable (<20 copies) by polymerase chain reaction and positive if EITHER loss-to-follow up and no lab data or virus was detected greater than 20 copies. | 24 weeks post-initiation of treatment (12 weeks post-completion of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR 48 | Sustained Viremic Response at 48 weeks post-completion of treatment (SVR48). Participants Achieving SVR48 had a negative hepatitis C real time polymerase chain reaction (RT-PCR) test at 48 weeks after end of treatment. Participants who Did Not Achieve SVR48 had a positive hepatitis C RT-PCR test at 48 weeks after end of treatment. | 60 weeks post-initiation of treatment (48 weeks post-completion of treatment) | 
| Discontinuation Rate or Lost To Follow Up | Percentage of patients discontinuing medications prior to completion of 12 weeks or being lost to follow up, defined as inability to reach patient after 3 attempts and patients not following up with primary endpoint labs (SVR 12, 48) | Study duration (60 weeks) | 
| NS5A Resistance | Percentage of patients with genotype 1a and NS5A Resistance-Associated Variants (RAVs) | At Study Screening/Enrollment | 
| Medication Adherence | Adherence determined by client/subject self-reported medication adherence measured by percentage of pills taken on a monthly basis. Categorically separated into < 90% adherence, 90-99% adherence, 100% adherence. | 12 weeks (duration of treatment) | 
| Injection Drug Use Relapse (IDU) | Self reported relapse IDU following HCV treatment (MAT arm) | Duration of study (60 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PWID, Hepatitis C, HCV, People Who Inject Drugs, Medication Assisted Therapy, MAT, Needle Exchange Program