Clinical trial NCT04652804: Supporting Treatment Outcomes Among PWID
Official title: A Precision Randomized Trial to Evaluate the Impact of Tailored Hepatitis C Virus (HCV) Treatment Adherence Support on HCV Treatment Outcomes in HIV/HCV Co-infected and HCV Mono-infected People Who Inject Drugs (PWID) in India.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatitis C
HIV Coinfection
Keywords: Patient Navigation
Treatment Adherence
People who inject drugs (PWID)
Directly Observed Therapy (DOT)
India
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: YR Gaitonde Centre for AIDS Research and Education
name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2020-12-03
Enrollment: 3000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 3-arm, individual-level randomized clinical trial, in which treatment assignment probabilities vary according to participants' estimated propensity for treatment failure at baseline (precision randomization). Minimal risk individuals have a higher likelihood of being allocated to lower intensity intervention and elevated risk individuals have higher likelihood of being allocated to higher intensity intervention.
Primary purpose: TREATMENT

Brief summary: The goal of this study is to improve HCV care continuum outcomes for people who inject drugs (PWID), reduce potential onward transmission to others and improve HIV outcomes among those who are HIV/HCV coinfected. The study will evaluate whether HCV treatment outcomes (sustained virologic response, treatment completion, adherence) and post treatment outcomes (HCV reinfection, HIV viral suppression) in HCV mono- and HIV/HCV co-infected PWID can be optimized by tailoring treatment support in 7 PWID-focused integrated HIV/HCV prevention and treatment centers in India.

Detailed description: The primary objective is to evaluate whether the intensity of treatment adherence support affects sustained virologic response rates in HCV mono- and HIV/HCV co-infected participants receiving HCV direct-acting antivirals (DAA) in PWID-focused centers. Secondary objectives are: 1. To evaluate whether the intensity of treatment adherence support affects HCV treatment completion rates. 2. To evaluate whether the intensity of treatment adherence support affects HCV treatment adherence. 3. To estimate the incidence and correlates of HCV reinfection among HCV mono- and HIV/HCV coinfected PWID who achieve HCV cure. 4. To evaluate the impact of HCV cure on HIV viral suppression among HIV/HCV coinfected PWID.

Investigators will evaluate this via a 3-arm, individual-level randomized clinical trial, in which treatment assignment probabilities vary according to participants' estimated propensity for treatment failure at baseline (precision randomization). An estimated 3,000 persons will be enrolled and randomized at 7 community-based integrated care centers (ICCs) across India across a duration of 18 - 24 months. Data from these 7 ICCs on early HIV treatment refills/viral suppression (3-6 months after antiretroviral therapy (ART) initiation) will be used to develop and validate an algorithm to predict propensity for HCV treatment failure. Prior to treatment initiation, each participant will undergo a questionnaire to capture information on barriers/ facilitators to treatment adherence identified in the prediction model in order to determine the propensity for HCV treatment failure (minimal or elevated risk). Individuals will be preferentially randomized to the support level that matches their failure risk. Those at elevated risk for treatment failure will be randomized at an allocation ratio of 3:2:1 for Arm 3 (high intensity support), Arm 2 (medium intensity support) and Arm 1 (low intensity support), respectively. Conversely, those at minimal risk will be randomized at a ratio of 1:2:3 to Arm 3 (high intensity support), Arm 2 (medium intensity support) and Arm 1 (low intensity support), respectively. Participants and study staff will be blinded to the risk classification (minimal, elevated) but, because of the nature of the interventions, blinding to intervention assignment is not possible.

Persons will be treated for HCV according to the standard of care in India. Minimal laboratory monitoring will be used except when clinically indicated. Participants with decompensated cirrhosis will be excluded from treatment.

All HIV/HCV co-infected participants and those HCV monoinfected participants who achieve SVR will be followed post-treatment. These individuals will be followed every six months after the SVR assessment to assess HCV reinfection and HIV viral suppression (among HIV/HCV coinfected participants) for up to 30 months after SVR.

Eligibility criteria: Inclusion Criteria:

* Registered for care at an Integrated Care Center (ICC) in one of the 7 field sites.
* Active HCV infection confirmed by a detectable HCV RNA by polymerase chain reaction (PCR) (HCV RNA ≥ 30 copies/ml) within 90 days prior to study entry.
* Liver disease stage defined as non-cirrhotic or compensated cirrhotic (metric/diagnostic criteria used for fibrosis staging) within 90 days prior to study entry.

  i. Albumin \>3.0 g/L. ii. Hemoglobin \>8.0 g/dL for women; \>9.0 g/dL for men. iii. Platelet count \>50,000/mm3. iv. Calculated creatinine clearance (CrCl) using Cockcroft-Gault method \>30 mL/min. v. Aspartate aminotransferase (AST/SGOT) \<10 times the upper limit of the normal range (ULN). vi. Alanine aminotransferase (ALT/SGPT) \<10 times the ULN. vii. Total bilirubin \<1.5 times the ULN for participants not on atazanavir (ATV) and \<3 times the ULN for participants on ATV. viii. International normalized ratio (INR) \<1.5 times the ULN.
* Life expectancy greater than 1 year (as determined by study clinician)
* Willing to initiate HCV treatment
* Agree to be randomized to an adherence support strategy
* Ability and willingness to provide written informed consent
* Female participants of reproductive potential must not be pregnant
* All female participants of reproductive potential must agree not to participate in a conception process
* All female participants of reproductive potential must agree to use at least one reliable form of contraceptive while receiving protocol-specified medication, and for 6 weeks after stopping the medication.

Exclusion Criteria:

* Psychologically unfit to provide written informed consent.
* Planning to migrate within the next six months.
* Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation.
* Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry.
* In HIV positive participants, presence of active or acute AIDS-defining opportunistic infections within 30 days prior to study entry.
* Use of prohibited medications within the past 14 days prior to study entry.
* Evidence of decompensated liver disease on clinical exam.
* Evidence of active tuberculosis.
* Evidence of chronic hepatitis B infection (HBsAg positive).
* Currently on HCV treatment.
* Prior history of DAA-based HCV treatment
* Confirmed active SARS CoV-2 infection or suspected active SARS CoV-2 infection at enrollment.
* Currently nursing (breastfeeding).

Primary outcomes:
measure: Sustained Virologic Response (SVR) by Intervention Group Stratified by Defined Risk for Treatment Failure (Minimal vs Elevated)
timeFrame: Between 10 and 60 weeks after scheduled end of treatment.
Secondary outcomes:
measure: HCV Treatment Completion
timeFrame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
measure: Adherence >90% (Self-report)
timeFrame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
measure: Adherence >90% (Medication Records)
timeFrame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
measure: Adherence Level (Self-report)
timeFrame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
measure: Adherence Level (Medication Records)
timeFrame: Measured at the end of prescribed course of treatment (12 or 24 weeks)
measure: HCV Reinfection
timeFrame: Measured at 6 month intervals after confirmation of SVR for up to 36 months.
measure: HIV Viral Suppression Among HIV/HCV Coinfected Participants
timeFrame: After assessment of SVR for up to 36 months.
Other outcomes:
measure: Exploratory Outcome Measure: Medication for Opioid Use Disorder (MOUD) Initiation
timeFrame: Measured daily from Entry Visit to post SVR for up to 36 months
measure: Exploratory Outcome Measure: Medication for Opioid Use Disorder Retention
timeFrame: Measured daily from Entry Visit to post SVR for up to 36 months
measure: Exploratory Outcome Measure: Quality of Life
timeFrame: Measured at 6 month intervals at the SVR visit and post SVR for up to 36 months.
measure: Exploratory Outcome Measure: Mortality
timeFrame: Measured from Entry visit to post SVR for up to 36 months.
measure: Exploratory Outcome Measure: Cost Effectiveness of Tailored Support Options (Low, Medium and High Intensity)
timeFrame: Measured at weekly intervals starting from Entry visit to SVR visit (up to 12 weeks after treatment completion).
measure: Exploratory Outcome Measure: Acceptability of Low, Medium and High Intensity Interventions
timeFrame: Qualitative interviews will be conducted between the end of treatment visit and the SVR visit (up to 12 weeks after treatment completion).
Locations:
city: Chennai
country: India
facility: YR Gaitonde Centre for AIDS Research and Education
state: Tamil Nadu
Study officials:
affiliation: Johns Hopkins University School of Medicine and Y.R. Gaitonde Centre for AIDS Research and Education
name: Sunil S Solomon, PhD MBBS MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Johns Hopkins Bloomberg School of Public Health
name: Shruti H Mehta, PhD MPH
role: PRINCIPAL_INVESTIGATOR
References: