Pharmacist-led Hepatitis C Management

Study Overview
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Brief Summary
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Hepatitis C virus (HCV) continues to disproportionately affect vulnerable and marginalized persons in Canada. During the interferon treatment era, certain circumstances precluded individuals from receiving treatment, most notably mental health concerns or active substance use. In addition to the tolerability and efficacy of all-oral direct acting antivirals (DAAs), novel diagnostic strategies have also increased engagement in the care cascade. Point-of care and/or dried blood spot antibody as well as RNA testing allow for diagnosis without the need for phlebotomy, a major barrier for those with a history of past or current injection drug use. Despite these advances in diagnostic streamlining and increased cure rates, engagement post-diagnosis continues to be a major gap. Although the exact mechanism of HCV acquisition may not be clear - people who inject drugs, persons who are street-involved or low-income, or persons who are difficult-to-reach for other reasons, often experience both structural and geographic challenges to obtaining care. Community pharmacists may be the first point of contact for higher risk populations and may avoid testing and/or treatment for fear of judgement or poor treatment in hospital/specialist settings. While studies have demonstrated the feasibility of treating people receiving opioid against therapy (OAT), it remains unclear whether Canadian pharmacists can safely and effectively screen, and/or confirm HCV, work-up patients for HCV treatment, and prescribe with minimal oversight. If this model proves successful, it may have global utility especially in areas of the world where pharmacists are the initial point of contact for healthcare issues. The aim of this study is to determine whether being tested and linked care and treatment will be more effective in a community pharmacy than a referral to a tertiary care hospital for management of HCV among people on stable OAT, or other populations who experience barriers to care but use community pharmacy services.

Official Title
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Pharmacist-led Hepatitis C Diagnosis and Rapid Management - in Community

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Behavioral: Pharmacist-Led care
* Behavioral: Standard of Care (Hepatology)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCV infection HCV RNA > 1,000 IU/mL Aged 18 to 80 Willingness and capacity to provide informed consent Exclusion Criteria: Presence of or history of decompensated cirrhosis. This will be defined as evidence of clinical decompensation (history of either ascites, variceal hemorrhage, or hepatic encephalopathy/confusion), and Child-Pugh-Turcotte and Model for Endstage Liver Disease (MELD) score will also be used to assess this using laboratory investigations and clinical findings. Platelets < 75,000/mm3, total albumin <35 g/L, total bilirubin (total and direct) >34.2 μmol/L, International Normalized Ratio (INR) >1.5 History of current or past hepatocellular carcinoma Hepatitis B virus (HBV) co-infection as indicated by positive testing for hepatitis B surface antigen (HBsAg +ve)or untreated HIV co-infection Prior HCV antiviral therapy with direct-acting antivirals with or without peginterferon/ribavirin Chronic liver disease other than mild non-alcoholic or alcoholic fatty liver disease from a cause other than HCV Significant co-morbid illness that precludes inclusion in the opinion of the investigator Life expectancy of less than 1 year. If clarity is required, the provider who delivered the diagnosis will be contacted. Pregnancy/breast-feeding/inability to use contraception Use of concomitant contraindicated drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Screening, evaluation and treatment at an outpatient pharmacy compared to referral to hepatology clinics
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Community Pharmacist-Led<br>Patients in Arm 1 will receive care and treatment at their home pharmacy and be evaluated and treated by a community pharmacist under medical directives and with study oversight. | Behavioral: Pharmacist-Led care<br>* Rapid testing in a community pharmacy, with rapid linkage to care and treatment that is pharmacist-led<br>|
| Active Comparator: Academic hepatology<br>Patients in Arm 2 will be evaluated and treated by hepatologists at the Toronto Centre for Liver Disease. | Behavioral: Standard of Care (Hepatology)<br>* Rapid testing in a community pharmacy, with standard of care referral to academic hepatology<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intention to treat by Completion Rates | Intention to treat direct acting antiviral (DAA) completion rates in non-cirrhotic or compensated cirrhotic patients treated with DAAs in pharmacist-led programs in community pharmacies, compared to treatment completion rates with referral and treatment in tertiary care hepatology (Toronto Centre for Liver Disease). | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained Virologic Response by Intention-to-Treat | Compare Sustained Virologic Response rates by Intention to treat in both sites. | 24 months | 
| Sustained Virologic Response by modified Intention-to-Treat | Compare the rates of Sustained Virologic Response by modified Intention to treat (including all participants who take at least one dose of medication) | 24 months | 
| Sustained Virologic Response by Per Protocol analysis | Compare the rates of Sustained Virologic Response by per protocol analysis including all individuals who complete treatment in both groups. | 24 months | 
| Hepatitis C Community seroprevalence in downtown Toronto | Determine the seroprevalence of HCV among individuals tested in downtown Toronto. | 18 months | 
| Community Pharmacist Fibrosis Identification | Comparison of pharmacist-assessed fibrosis stage vs fibrosis stage assessed by hepatologist (gold standard) | 18 months | 
| Community Pharmacist Decompensation Identification | Comparison of pharmacist-assessed hepatic decompensation score vs hepatic decompensation assessed by hepatologist (gold standard) | 18 months | 
| Minimum Mean Time-to-Treatment | Determine the minimum mean time-to-treatment initiation in both groups | 18 months | 
| Community Appointment Adherence | Assess appointment adherence in both arms | 24 months | 
| Medication Adherence | Assess self-reported medication adherence at both sites | 18 months | 
| Quality of Life and Substance Use | Evaluate quality of life for patients with chronic liver disease (CLDQ-HCV) before and after treatment (endpoint and SV12) at both sites. | 24 months | 
| Substance Use | Evaluate the Maudsley Addiction Profile (MAP) before and after treatment (endpoint and SV12) at both sites. | 24 months | 
| Patient Understanding and Satisfaction | Compare patient understanding and satisfaction with HCV treatment with the Hepatitis Patient Satisfaction Questionnaire (HPSQ) | 24 months | 
| Reinfection | Assess rates of reinfection in patients who achieve Sustained Virologic Response, at 48 weeks. | 24 months | 
| Patient empowerment | Compare measure of patient empowerment by treatment-arm using the Health Care Empowerment (HCE) survey | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Point-of-care testing, Rapid access to treatment, Pharmacist-led, Service co-localization