Antiviral Pharmacology and Adherence in Drug Users
2 other identifiers
interventional
73
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Nov 2015
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 3, 2015
CompletedFirst Posted
Study publicly available on registry
October 9, 2015
CompletedStudy Start
First participant enrolled
November 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2021
CompletedMarch 8, 2022
March 1, 2022
4.3 years
June 3, 2015
March 4, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Compare each individual's modeled estimate of ledipasvir and metabolites of sofosbuvir (GS-331007 and GS-331007-TP) steady state concentrations (Css) from non-linear mixed effects modeling to Css in subjects receiving DOT vs. WOT.
12 weeks
Quantify GS-331007-TP concentrations in dried blood spots as a function of adherence (doses taken/doses prescribed).
12 weeks
Estimate the probability of HCV cure as a function of adherence using logistic regression.
24 weeks
Study Arms (2)
Sofosbuvir/Ledipasvir with Directly Observed Therapy (DOT)
OTHERParticipants 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.
Sofosbuvir/Ledipasvir with Wirelessly Observed Therapy (WOT)
OTHERParticipants on WOT will be provided the Wisepill portable medication dispenser.
Interventions
Eligibility Criteria
You may qualify if:
- 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
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Colorado, Denverlead
- Denver Health and Hospital Authoritycollaborator
- National Institute on Drug Abuse (NIDA)collaborator
- Gilead Sciencescollaborator
Study Sites (1)
University of Colorado Anschutz Medical Campus
Aurora, Colorado, 80045, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Jennifer J Kiser, PharmD
University of Colorado, Denver
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- OTHER
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 3, 2015
First Posted
October 9, 2015
Study Start
November 1, 2015
Primary Completion
March 1, 2020
Study Completion
June 1, 2021
Last Updated
March 8, 2022
Record last verified: 2022-03