Opportunistic treatment of hepatitis C virus infection (OPPORTUNI-C): study protocol for a pragmatic stepped wedge cluster randomized trial of immediate versus outpatient treatment initiation among hospitalized people who inject drugs

Abstract

Background: Scaled-up direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection among people who inject drugs (PWID) is crucial to reach the World Health Organization HCV elimination targets within 2030. One of the critical obstacles to HCV care in this population is the lack of treatment models within specialist healthcare adapted to marginalized individuals.

Methods: OPPORTUNI-C is a pragmatic stepped wedge cluster randomized trial comparing the efficacy of immediate initiation of HCV treatment with the current standard of care among PWID admitted for inpatient care. Screening for HCV RNA will be performed as soon as possible after admission. The intervention includes immediate non-invasive liver disease assessment, counseling, and initiation of pan-genotypic DAA treatment with individualized follow-up. Standard of care is a referral to outpatient care at discharge. To mimic usual clinical practice as closely as possible, we will use a pragmatic clinical trial approach utilizing clinical infrastructure, broad eligibility criteria, flexible intervention delivery, clinically relevant outcomes, and collection of data readily available from the electronic patient files. The stepped wedge design involves a sequential rollout of the intervention over 16 months, in which seven participating clusters will be randomized from standard of care to intervention in a stepwise manner. Randomization will be stratified according to cluster size to keep high prevalence clusters separated. The trial will include approximately 220 HCV RNA positive individuals recruited from departments of internal medicine, addiction medicine, and psychiatry at Akershus University Hospital, Oslo University Hospital, and Lovisenberg Diaconal Hospital, Oslo, Norway. Individuals not able or willing to give informed consent and those with ongoing HCV assessment or treatment will be excluded. The primary outcome is treatment completion, defined as dispensing of the final prescribed DAA package from the pharmacy within 6 months after inclusion. Secondary outcomes include treatment uptake, virologic response, reinfection incidence, and resistance-associated substitutions.

Discussion: Representing a novel model of care suited to reach and engage marginalized PWID in HCV care, this study will inform HCV elimination efforts locally and internationally. If the model proves efficacious and feasible, it should be considered for broader implementation, replacing the current standard of care.

Trial registration: ClinicalTrials.gov, NCT04220645. Registered on 7 January 2020.

Keywords: Direct-acting antivirals; Hepatitis C virus; Model of care; People who inject drugs; Pragmatic clinical trial; Reinfection; Resistance-associated substitutions; Stepped wedge cluster randomized trial; Study protocol.

Conflict of interest statement

HM has received advisory boards fees and lecture fees from Gilead, Abbvie, and MSD. OD has received grant and research support from Abbvie, Gilead, and MSD; advisory boards fees from Gilead and MSD; and lecture fees from Abbvie and MSD. The other authors report no competing interests.

Figures

Fig. 1

The stepped wedge cluster randomized trial design of OPPORTUNI-C. Seven clusters will be sequentially assigned to change from standard of care to intervention in a random order. Blank cells represent control observations and shaded cells represent intervention observations. The length of each step is 2 months

Fig. 2

CONSORT diagram showing flow of study participants in OPPORTUNI-C

Fig. 3

Schedule of enrolment, interventions, assessments, and visits for participants in OPPORTUNI-C

Fig. 4

Diagram showing the estimated average number of included participants needed per cluster for each step of the study. Shaded cells represent intervention periods