Evaluation of HepCure Toolkit to Improve Harvoni Adherence

Study Overview
=================
Brief Summary
-----------------
There is limited data outside of clinical trials on adherence to once daily ledipasvir/sofosbuvir regimens. Many patients present with known barriers to medication adherence including untreated psychiatric illness and substance use disorders, cognitive impairment, and low health literacy. The goal of this study is to evaluate the baseline level of adherence to ledipasvir/sofosbuvir in a real-world clinic population and compare this to the level of adherence in patients provided with additional adherence support. Medication adherence in this study will be evaluated using AdhereTech, a wireless pill monitoring device that measures the dosage and time a medication was taken. Using cellular technology, AdhereTech can be used passively to collect data on when a medication is taken, when a refill is needed, and how often the bottle is opened. AdhereTech also can be used actively to monitor adherence and provide feedback to subjects using the device. When actively monitoring, AdhereTech can be set up to provide live feedback to a subject by lighting up, sounding chimes, and sending phone/text/email alerts to remind patients to take their medication (see attached PowerPoint presentation). HepCure is a web-based tool kit in the form of a dashboard for medical providers (MDs and NPs) and an application (or app) for patients. The app allows patients to become active participants in their treatment by enabling them to set medication reminders, record doses taken, and communicate their adherence to their medical provider using the provider dashboard.

Detailed Description
-----------------
Primary Objectives: The study will be conducted in two phases with the following aims: (1) To passively assess the adherence to hepatitis C virus (HCV) treatment with ledipasvir/sofosbuvir using a wireless pill monitoring device in 33 patients (Phase 1, months 1-3). (2) To test the impact on adherence of using the active wireless pill monitoring device in conjunction with the HepCure web-based tool kit in 66 patients (Phase 2, months 4-9). Participants in phase 2 will be randomized 1:1 to one of two conditions: (a) Patients using the HepCure patient app linked to a provider using the HepCure Provider Dashboard; AdhereTech passively monitoring adherence. (b) Patients using the HepCure patient app linked to a provider using the HepCure Provider Dashboard; AdhereTech actively monitoring adherence (chimes and reminders enabled). Secondary Objectives: The study design allows us to compare the additive effect on adherence of the HepCure provider toolkit and the HepCure provider toolkit + active AdhereTech reminder system. Primary Endpoints: The primary study endpoints are taking and timing adherence as assessed by electronic monitoring. There are numerous methods of assessing adherence to medication. They each have their strengths and weaknesses, and some are only feasible in the research but not clinical setting. The most commonly used methods of assessing adherence are (1) provider assessment, (2) structured self-report (3) pharmacy refill data (4) electronic monitoring (5) pill counts and (6) directly observed therapy. Electronic monitoring technology has been widely used in research studies of HIV medication adherence and is regarded by many as the most accurate method of assessing medication adherence (Weiss et al. 2009). In this method, the medication bottle cap has a microchip which records all openings and closings of the bottle. This microchip provides the researcher with a precise record of the date and time of each bottle opening. This method has been shown to be closely associated with random home pill count (Bangsberg et al., 2001a), viral suppression (Bangsberg et al., 2000; Paterson et al., 2000; Arnsten et al., 2001; Walsh et al., 2002b; Moss et al., 2004), and drug resistance (Walsh et al., 2002b). Studies have consistently found that provider assessment of adherence is poor (Bangsberg et al., 2001b; Gross et al., 2002; and Miller et al., 2002). Self-reported adherence tends to provide an over-estimate of actual adherence (Weiss et al. 2009). Pharmacy refill data is best employed when patients use one pharmacy for all prescriptions, pharmacy data are easily accessible to the clinician by computer, and prescriptions are not automatically delivered without the patient needing to request them or pick them up. Patients in clinical research studies are often asked to bring their medication to study visits so that the change in the number of pills (accounting for refills) since the last visit can be used to assess adherence. Potential problems associated with these announced pill counts are that patients may forget to bring their medication to study visits, and nonadherent patients may throw out pills prior to the visit (pill dumps) to avoid being labeled nonadherent. While directly observed therapy (DOT) provides a highly accurate assessment of adherence, the cost and intrusiveness of observing all doses of medication ingestion make it an impractical method of ARV adherence assessment, except in very specific settings (e.g., prisons or nursing homes).

Official Title
-----------------
Evaluation of HepCure Toolkit to Improve Harvoni Adherence

Conditions
-----------------
Hepatitis C, Medication Adherence

Intervention / Treatment
-----------------
* Other: HepCure ToolKit
* Device: AdhereTech Active Features
* Other: AdhereTech Passive Monitoring


Participation Criteria
=================
Eligibility Criteria
-----------------
No one will be excluded based on gender, age, race, or ethnic group. Inclusion criteria Phase 1 and 2: Age18 years and older Being prescribed Harvoni for treatment of HCV and not yet started treatment Speak and read English Inclusion criteria Phase 2 Only: Possessing a smartphone device Ability to use a smartphone device Registered with a physician currently using the HepCure Provider Dashboard. Speak and read English Exclusion criteria: Individuals with diminished mental capacity who are unable to give informed consent Prisoners Participants who do not speak or write in English as a primary language Participants who are unable to speak and read English Participants who are expected to have difficult with regular access to smart phone device.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 89 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: AdhereTech Passive Monitoring<br>Patients not using the HepCure patient app while AdhereTech passively monitors adherence (no chimes or reminders). | Other: AdhereTech Passive Monitoring<br>* AdhereTech passively monitors adherence (no chimes or reminders)<br>|
| Experimental: HepCure Toolkit<br>Patients using the HepCure patient app linked to a provider using the HepCure Provider Dashboard with AdhereTech passively monitoring adherence (no chimes or reminders). | Other: HepCure ToolKit<br>* HepCure is a web-based tool kit in the form of a dashboard for providers and an application (or app) for patients. The app allows patients to become active participants in their treatment by enabling them to enter prescribed treatment, add medications to Pill Box, log doses, visualize adherence, and includes several additional resources.<br>Other: AdhereTech Passive Monitoring<br>* AdhereTech passively monitors adherence (no chimes or reminders)<br>|
| Experimental: HepCure Toolkit and AdhereTech Active Features<br>Patients using the HepCure patient app linked to a provider using the HepCure Provider Dashboard and with AdhereTech actively monitoring adherence (chimes and reminders enabled). | Other: HepCure ToolKit<br>* HepCure is a web-based tool kit in the form of a dashboard for providers and an application (or app) for patients. The app allows patients to become active participants in their treatment by enabling them to enter prescribed treatment, add medications to Pill Box, log doses, visualize adherence, and includes several additional resources.<br>Device: AdhereTech Active Features<br>* AdhereTech, a wireless pill monitoring device that measures the dosage and time a medication was taken. It is a HIPAA-compliant, FDA-registered Class I medical device. Using cellular technology, AdhereTech can be used passively to collect data on when a medication is taken, when a refill is needed, and how often the bottle is opened. AdhereTech also can be used actively to monitor adherence and provide feedback to subjects using the device. When actively monitoring, AdhereTech can be set up to provide live feedback to a subject by lighting up, sounding chimes, and sending phone/text/email alerts to remind patients to take their medication.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication Adherence | AdhereTech bottles use sensors to provide a timestamp of when the bottle cap was open and closed. | up to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HCV RNA | The Sustained Viral Response (SVR) outcome will be monitored until the patient attains sustained virologic response post-treatment measured by HCV RNA from medical record. | up to 9 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis C, Adherence, Adheretech, HepCure, Telehealth, Health apps