Smartphone Based aDOT Treatment With Fixed-Dose Elbasvir and Grazoprevir in PWIDs

Study Overview
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Brief Summary
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People who Inject Drugs (PWIDs) constitute 60% of the approximately 5 million people in the United States infected with hepatitis C virus (HCV). Successful HCV treatment leading to sustained viral response (SVR) is associated with increased survival, but to date successful treatment of PWIDs has been limited. Treatment of PWIDs is complex due to addiction, mental illness, poverty, homelessness, lack of positive social support, poor adherence-related skills, low motivation and knowledge, and poor access to and trust in the health care system. At Albert Einstein College of Medicine, the investigators have developed a multidisciplinary model of HCV care that integrates on-site primary care, substance abuse treatment, and HCV-related care within opiate agonist treatment clinics. To optimize HCV treatment outcomes, the investigators have introduced directly observed therapy (DOT). In the DOT model, one daily dose of oral HCV medication is administered with methadone. However, DOT is not feasible for PWIDs who are not enrolled in methadone maintenance treatment programs, and is less effective for methadone-maintained PWIDs who do not attend the methadone clinics every day. In addition, DOT has been used for decades both to measure and maximize adherence for treatment of tuberculosis infection, but the cost and logistical complexity of administering DOT for large HCV clinical programs would be prohibitive.

Detailed Description
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Automated DOT (a-DOT), a smartphone app that uses facial recognition software and advanced features to detect non-ingestion, combines the accuracy of in-person DOT with the convenience of real-time centralized data collection and monitoring. Adding a daily side effect diary to a-DOT will further allow precise tracking of timing of both medication ingestion and side effects which may be compromising adherence. Zepatier (elbasvir and grazoprevir) is a new once-daily fixe-dose combination tablet which has achieved high rates of SVR ranging from 94 to 97 percent in genotype-1 infected patients including those with HIV/HCV coinfection and renal impairment. Zepatier is administered for 12 to 16 weeks, depending on HCV genotype, prior treatment history, and the presence of certain baseline NS5A polymorphisms (1a only). By administering Zepatier via this innovative a-DOT platform, the investigators hypothesize that PWIDs treated in real-wrold settings can be successfully treated with high rates of adherence and SVR. In this proposed 18-month trials, 75 PWIDs enrolled in opiate agonist treatment (genotypes 1a and 1b) with chronic HCV will be enrolled over a 12-month period, and randomized to either aDOT or treatment as usual (TAU). The investigators will recruit PWIDs from diverse community settings include a syringe exchange program (NYHRE), federally-qualified health center (Comprehensive Health Care Center), homeless shelter (The Living Room), and a methadone maintenance treatment program (Montefiore Wellness Centers). All patients (inlcuding treatment-experienced and HIVV/HCV coinfected subjects) will be treated with Zepatier-based regimens as per the standard of care. Rigorous data are necessary to judge the contribution of a-DOT to the success of HCV treatment in PWIDs. By performing a randomized trial of a-DOT HCV therapy (Zepatier with and without ribavirin), the investigators will evaluate the efficacy of a-DOT for improving HCV treatment outcomes among PWIDs.

Official Title
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Smartphone Based Automated-Directly Observed Treatment Improves Adherence and SVR to Fixed-Dose Elbasvir and Grazoprevir in PWIDs: A Randomized Control Trial

Conditions
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Hepatitis C, Medication Adherence

Intervention / Treatment
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* Device: AiCure
* Device: AiCure with gamification


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCV-infected (HCV RNA test above the limit of quantification at baseline) Genotypes/Subtypes: G1a or G1b Eligible for HCV treatment per 2016 AASLD/IDSA guidelines Willing to receive HCV treatment on-site at DoSA clinics Health care provider decision to treat patient with Zepatier-based therapy with or without ribavirin based on 2016 AASLD/IDSA guidelines Using illicit drugs (either opiates, cocaine, or benzodizepenes) within the last 6 months Age 18 or older Able to provide informed consent English or Spanish speaking Exclusion Criteria: Known hypersensitivity (allergy) to elbasvir, grazoprevir, or ribavirin Pregnant or breast-feeding

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AiCure App<br>Participants will use a-DOT technology called AiCure (a Smartphone App) to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. | Device: AiCure<br>* Smartphone App<br>* Other names: a-DOT, Smartphone App;|
| No Intervention: Treatment As Usual<br>Participants will receive treatment for ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks without using the AiCure app. | |
| Active Comparator: AiCure with gamification<br>Sub-group of participants will use a-DOT technology called AiCure (a Smartphone app) with gaming to track ingestion of fixed-dose Elbasvir and Grazoprevir, 1 tablet, 50mg-100mg of each drug, respectively, daily for 12 weeks. The gaming feature is to test whether competition encourages engagement and helps to increase adherence to the HCV medication. | Device: AiCure with gamification<br>* Smartphone App with gaming.<br>* Other names: a-DOT with gamification;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV Treatment Adherence | The amount of medication taken by each patient during the treatment period is expressed as a percentage (range 0-100%). Subjects will be classified as adherent if they receive at least 80% of the total dose of Zepatier. The numbers below denotes the mean percent of the medication the participants in each arm took. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HCV Treatment Completion | Participants will be considered to have completed treatment if they have completed at least 80% of the planned treatment course (e.g. at least 10 week of 12-week course). | 12 weeks | 
| Number of Participants With Sustained Viral Response (SVR) | HCV viral load undectable 12 weeks after treatment completion. Undetectable HCV viral load is defined as <15 IU/ml and target not detected. IU refers to international units.One of the main outcomes looked for was the amount of patients who achieved Sustained Virologic Response (SVR) at 12 weeks post treatment, which denotes a cure of Hepatitis C. | 12 weeks post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Resistance, Addiction, Sustained Viral Response, Adherence, Adverse Effects, Direct Acting Antiviral Agent, Chronic Hepatitis C, Resistance Development, Methadone Clinic, Primary Care, Directly Observed Therapy, Randomized Controlled Trial, Reinfection, Treatment Outcome, Patient Navigation, Multi-Site, Liver Disease, Intervention