HCV Treatment Initiation During Acute Psychiatric Admission

INSPIRE: Interventions for Screening and Treatment of Psychiatric Inpatients With HCV Resulting in Elimination

Hepatitis C virus (HCV) disproportionally affects certain populations, including those facing substance use and mental health challenges. In the past, many individuals with mental illness were not treated due to the psychiatric side-effects of interferon. However, the development of highly effective, direct-acting antivirals (DAA) has revolutionized HCV treatment such that cure rates are >95% with 8-12 weeks of simple, safe, and well-tolerated therapy.

A recent systematic review reported that across 13 North American studies, HCV prevalence among people admitted to psychiatric hospitals was a staggering 17.4% (13.2-22.6%). Despite these concerning figures, mental health facilities have not been a focus of HCV elimination efforts to date. The Centre for Addiction and Mental Health (CAMH) in Toronto is the largest mental health facility in Canada, with a psychiatric emergency department seeing ~35 patients per day with many admitted to the acute psychiatric units for safety and stabilization. Currently, psychiatric patients screened for HCV at CAMH have a 75% 'no show' rate at the Toronto Centre for Liver Disease (TCLD), which is located less than 5km away, suggesting that referral upon discharge is ineffective.

This study will be the first trial to evaluate whether it would be feasible and beneficial to initiate treatment during an acute psychiatric admission rather than referring to specialty upon discharge. The combination of broad HCV screening with rapid linkage to treatment has led to successful elimination of HCV within defined populations, so-called micro-elimination. The investigators hypothesize that HCV treatment can be effectively delivered by providers in psychiatric care facilities, which will improve treatment uptake over traditional referral models.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis C
• Intervention / Treatment: Other: HCV care provided by hospitalist during acute psychiatric admission

• Study Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mia Biondi, NP-PHC, PhD; Phone Number: 6476286461; Email: mia.biondi@mail.mcgill.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M6J 1H3
      • Recruiting
      • Centre for Addiction and Mental Health
      • Contact: Renee Logan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Chronic HCV infection, positive HCV RNA
2. Aged 18 to 80
3. Willingness and capacity to provide informed consent, or consent is provided by a substitute decision maker

Exclusion Criteria:

1. Presence of or history of decompensated cirrhosis (evidence of decompensation with history of either ascites, variceal hemorrhage, or hepatic encephalopathy)
2. Platelets < 75,000/mm3, total albumin <35 g/L, total bilirubin >34 μmol/L, INR >1.5
3. History of current or past hepatocellular carcinoma.
4. HBV (HBsAg +ve) co-infection or untreated HIV co-infection
5. Prior HCV antiviral therapy with DAA with or without peginterferon/ribavirin
6. Chronic liver disease other than mild nonalcoholic or alcoholic fatty liver disease from a cause other than HCV
7. Pregnancy/breastfeeding/inability to use contraception
8. Use of concomitant contraindicated medications

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Referral to outpatient specialty for HCV care; Acute psychiatric patients who test HCV RNA positive by OraQuick HCV Antibody Test will be referred for outpatient specialty follow-up at the Toronto Centre for Liver Disease (TCLD) where they will be assessed and offered treatment as per standard of care. TCLD referrals are triaged by clinicians unaware of the trial and prioritized based on urgency of treatment. Patients who do not attend the initial visit will be rescheduled. After 3 'no-show' visits, the person will not be scheduled again at TCLD and will be deemed a 'treatment failure' for the trial with subsequent HCV follow-up at the discretion of the CAMH provider, consistent with current practice.
Experimental: Receive HCV care during inpatient admission by a hospitalist; CAMH hospitalists covering the inpatient units will undergo a training designed for non-specialist providers, used in the ASCEND trial, which has already occurred. An algorithm-based work-up which has been used for non-specialist treaters in ECHO Liver, a Ministry-of-Health supported tele-mentoring program, will then be completed for all who test HCV RNA positive. Labs will be drawn by the hospital phlebotomist following a positive HCV RNA result from the Gene Xpert Viral Load Assay. At this time, a sample will also be obtained to send to for conventional HCV RNA quantification and genotyping.	Other: HCV care provided by hospitalist during acute psychiatric admission; HCV diagnosis and treatment will be conducted by a hospitalist during an acute psychiatric admission at CAMH

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SVR12 by intention to treat (ITT) in each arm	To determine whether screening for HCV using rapid diagnostics during an acute psychiatric admission with inpatient initiation of HCV treatment is superior to standard post-discharge referral and treatment by intention to treat (ITT).	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SVR12 by modified intention to treat (mITT) in each arm	To determine whether screening for HCV using rapid diagnostics during an acute psychiatric admission with inpatient initiation of HCV treatment is superior to standard post-discharge referral and treatment by modified intention to treat (mITT).	24 months
HCV relapse rate	To compare the HCV viral relapse rate in both arms (re-appearance of HCV RNA in those undetectable at end of treatment; relapse distinguished from reinfection by sequencing of the recurrent HCV RNA and comparing to baseline).	24 months
HCV seroprevalence rates	To determine HCV seroprevalence rates among acute vs addictions patients admitted to CAMH.	12 months
HCV RNA positivity rates	To determine HCV RNA positivity rates among acute vs addictions patients admitted to CAMH.	12 months
CAMH staff acceptability of POC antibody and RNA testing	CAMH staff involved in the trial will be asked to particiapte in an acceptibility survey regarding rapid POC antibody and RNA testing on the acute units.	12 months
Concordance of POC HCV RNA with HCV RNA by phlebotomy	To determine concordance of POC HCV RNA (GeneXpert) with HCV RNA by phlebotomy (Abbott RealTime).	12 months
Minimum and mean times from diagnosis to treatment initiation	Evaluate the mean and minimum times to treatment initiation in both arms, and compare.	24 months
Adherence with out-patient follow-up visits	Evaluate and compare out-patient follow-up visit adherence in both arms.	24 months.
Adherence to HCV treatment, by HCV regimen	Evaluate and compare both arms for medication adherence (patient self-report and pill count), and variance by medication regimen.	24 months.
Adverse events while on HCV treatment	To determine and compare adverse events in both arms while patients are on treatment.	18 months.
HCV Reinfection	Reinfection rates by the end of the defined as HCV RNA detectability after prior SVR with demonstration of distinct viral sequence from baseline sample to distinguish	24 months.

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Centre for Addiction and Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: September 29, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): May 5, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Treatment; Hospital; Hepatitis C; Psychiatric
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Hepatitis C
• Other Study ID Numbers: 20-5188

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No