Antiviral Pharmacology and Adherence in Drug Users

NCT ID: NCT02573376

Last Updated: 2022-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2021-06-30

Brief Summary

Approximately one half of all Americans living with Hepatitis C virus (HCV) are drug users, yet they are the least likely to receive HCV treatment. Drug users are presumed non-adherent and therefore denied potentially life-saving therapy. This assumption can only be confirmed or dispelled through prospective pharmacologic and adherence studies in this population. Such studies would be greatly enhanced by an objective, quantitative measure of adherence which does not currently exist in the HCV field. Through the work proposed in this application, sixty HIV/HCV co-infected drug users will be treated with direct acting antiviral agents (DAA) and randomized to receive directly observed DAA therapy (DOT) vs. no directly observed therapy (no-DOT). Patients randomized to no-DOT will have wirelessly observed therapy (WOT) which involves use of a portable medication dispenser that sends a signal to a server with the date and time when the dispenser is opened. In Aim 1, DAA concentrations will be compared in those randomized to DOT vs. no-DOT. DAA pharmacokinetics will also be defined accounting for clinical factors like degree of hepatic impairment and use of concomitant recreational and antiretroviral drugs. The goal is to quantify adherence in this population and the effect of variable adherence on drug concentrations. In Aim 2, DAA concentrations (plasma, cellular, hair) will be linked with adherence patterns identified using WOT and DOT. The goal is to identify a drug concentration biomarker that predicts adherence in this population. In Aim 3, the relationship between DAA adherence (as measured by WOT and DOT and drug concentrations) and rate of cure will be established. The goal is to define the degree of adherence needed for HCV cure.

Conditions

HEPATITIS C; Virus, Human Immunodeficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Sofosbuvir/Ledipasvir with Directly Observed Therapy (DOT)

Participants randomized to vDOT will be provided a smart phone with cellular service and will be pre-programmed with the mobile phone-based video application and contact information for study personnel.

Group Type: OTHER

Directly Observed Therapy

Intervention Type: BEHAVIORAL

Sofosbuvir/Ledipasvir with Wirelessly Observed Therapy (WOT)

Participants on WOT will be provided the Wisepill portable medication dispenser.

Group Type: OTHER

Wirelessly Observed Therapy

Intervention Type: BEHAVIORAL

Interventions

Directly Observed Therapy

Intervention Type: BEHAVIORAL

Wirelessly Observed Therapy

Intervention Type: BEHAVIORAL

Other Intervention Names

DOT; WOT

Eligibility Criteria

Inclusion Criteria

• Ability to give informed consent
• HIV-infected men and women
• Chronic HCV infection as documented by quantifiable HCV RNA
• HCV genotype 1, 4, 5, 6
• 18-70 years of age
• Willingness and ability to comply with study procedures, including DOT, WOT, and biweekly clinic visits
• Considered an active drug user by HCV provider and self-reported drug use within the past month

Exclusion Criteria

• Glomerular filtration rate < 30 mL/min/1.73 m2
• Receipt of prior HCV treatment and radiographic, histologic, or clinical evidence of cirrhosis
• Decompensated liver disease (i.e., ascites, history of esophageal variceal bleeding, hepatic encephalopathy)
• Medications not recommended per the SOF/LDV prescribing information (e.g., tipranavir and other P-gp inducers, tenofovir disoproxil fumarate plus cobicistat, rosuvastatin, amiodarone)
• Any medical condition that in the opinion of the investigators will make it challenging to adhere to the study protocol, such as unstable heart disease or cancer
• Chronic Hepatitis B virus Infection
• For females, active pregnancy or any intent to become pregnant
• For both sexes, an unwillingness to use contraception during the study period
• On parole or impending sentencing

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Denver Health and Hospital Authority

OTHER

Sponsor Role: collaborator

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jennifer J Kiser, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Countries

United States

Other Identifiers

1R01DA040499-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

15-0809

Identifier Type: -

Identifier Source: org_study_id