A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study.

BACKGROUND AND AIMS: Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable. APPROACH AND RESULTS: We conducted a pragmatic randomized controlled trial (NCT02786537) to compare the effectiveness of DAAs for HCV genotype 1a or 1b on viral response, safety, tolerability, and medication nonadherence. Adults with compensated liver disease, HCV genotype 1, not pregnant or breastfeeding, and with health insurance likely to cover ledipasvir/sofosbuvir (LDV/SOF) were recruited from 34 US viral hepatitis clinics. Participants were randomized (± ribavirin) to LDV/SOF, elbasvir/grazoprevir (EBR/GZR), and paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD; treatment arm stopped early). Primary outcomes included sustained viral response at 12 weeks (SVR12), clinician-recorded adverse events, patient-reported symptoms, and medication nonadherence. Between June 2016 and March 2018, 1,609 participants were randomized. Among 1,128 participants who received ≥1 dose of EBR/GZR or LDV/SOF (± ribavirin), SVR12 was 95.2% (95% CI, 92.8%-97.6%) and 97.4% (95% CI, 95.5%-99.2%), respectively, with a difference estimate of 2.2% (-0.5% to 4.7%), falling within the "equivalence" interval (-5% to 5%). While most (56%) participants experienced adverse events, few were serious (4.2%) or severe (1.8%). In the absence of ribavirin, discontinuations due to adverse events were rare. Patient-reported symptoms and medication nonadherence were similar. Study limitations were dropout due to insurance denial and loss to follow-up after treatment, limiting the ability to measure SVR12. CONCLUSIONS: This pragmatic trial demonstrated high SVR12 for participants treated with EBR/GZR and LDV/SOF with few adverse effects. Overall, the two regimens were equivalent in effectiveness. The results support current HCV guidelines that do not distinguish between ribavirin-free EBR/GZR and LDV/SOF.

Experiences of an HCV Patient engagement group: a seven-year journey.

Historically, few publications exist where patient engagement in clinical studies is a driving force in study design and implementation. The Patient Centered Outcomes Research Institute (PCORI), established in 2010, employed a new model of integrating stakeholder perspectives into healthcare research. This manuscript aims to share the experience of a Patient Engagement Group (PEG) that has engaged in hepatitis C (HCV) clinical research alongside investigators conducting two studies funded by PCORI and to inspire others to get more involved in research that can impact our healthcare and health policies.There are many gaps in treating infectious diseases. Traditionally, treatment and research have been strictly clinical/medical approaches with little focus on the biopsychosocial aspects of individual patients. Our PEG reflected on its own personal experiences regarding how research design can affect study implementation by including patients who are normally excluded. We considered barriers to treatment, out of pocket costs, access to insurance, and patient race/ethnicity. Common themes were discovered, and four major topics were discussed. In addition, measures used in the two studies to collect patient data were considered, tested, and implemented by the group.We describe in detail how we were formed and how we have worked together with researchers on two PCORI funded projects over the past 7 years. We formulated and implemented guidelines and responsibilities for operating as a PEG as well as appointing a chair, co-chair, and primary author of this manuscript.Written from the perspective of a PEG whose members experienced HCV treatment and cure, we provide lessons learned, and implications for further research to include patients. PEGs like ours who are included as active partners in research can provide useful input to many areas including how patients are treated during clinical trials, how they interact with research teams, and how the clinical benefits of drugs or devices are defined and evaluated. PCORI believes engagement impacts research to be more patient-centered, useful, and trustworthy, and will ultimately lead to greater use and interest of research results by the patient and the broader healthcare community.

A randomized controlled trial of an integrated care intervention to increase eligibility for chronic hepatitis C treatment.

OBJECTIVES: Mental health and substance abuse (MH/SA) comorbidities are the most oft-cited reasons for deferral from peginterferon (PegIFN) therapy for chronic hepatitis C virus (HCV). We sought to determine whether an integrated care intervention (INT) for patients deferred from PegIFN owing to MH/SA could improve subsequent treatment eligibility rates. METHODS: In this randomized controlled trial, 101 HCV patients who were evaluated at two hepatology centers and deferred from antiviral therapy owing to MH/SA were enrolled. Participants were randomized to an INT (N=50) or standard of care (SC; N=51). The INT group received counseling and case management for up to 9 months. All participants underwent 3-, 6-, and 9-month clinical follow-up visits, where hepatologists, masked to group, re-evaluated patients for treatment eligibility. Standardized mood and alcohol use instruments were administered to all participants to aid clinicians in treatment decisions. RESULTS: Of 101 participants, the mean age was 48 years and 50% were men, 61% Caucasian, and 77% genotype 1. Patients were initially deferred owing to psychiatric issues (35%), alcohol abuse (31%), drug abuse (9%), or more than one of these reasons (26%). In an intent-to-treat analysis, 42% (21/50) of INT participants became eligible for therapy compared to 18% (9/51) of SC participants (P=0.009, relative risk (RR)=2.38, 95% confidence interval (CI) (1.21, 4.68)). When baseline predictors significant at P<0.10 in univariate models were entered into multivariate models adjusted for treatment group, only baseline depression remained significant (P=0.05, RR=0.98, 95% CI (0.96, 1.00)). With the exception of a model adjusted for genotype, treatment group remained significant in all models. CONCLUSIONS: This trial suggests that INTs can increase eligibility for HCV treatment and expand treatment to the underserved population with MH/SA comorbidities.