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DRug Use & Infections in ViEtnam - Hepatitis C (DRIVE-C)

Registration Number
NCT03537196
Lead Sponsor
ANRS, Emerging Infectious Diseases
Brief Summary

The study aims to assess the effectiveness of a model of hepatitis C screening and integrated care, targeting people who inject drugs (PWIDs) in Hai Phong, Vietnam. In a wider perspective, this model linked to mass screening through repeated Respondent Driven Sampling (RDS) surveys, to simplified treatment protocol, and to large community-based support to improve referral to care, retention in care, adherence to treatment and prevention of reinfection, may have the potential to eliminate HCV among PWIDs in this city.

Detailed Description

Objectives :

The primary objective of this study is to assess the effectiveness of a model of hepatitis C screening and integrated care targeting PWIDs in Hai Phong, Vietnam.

This model will encompass all steps involved in achieving HCV cure among PWIDs:

i) Mass detection of hepatitis C infection among PWIDs: in the community through a large community-based Respondent Driven Sampling survey (RDS); and in HIV out-patient clinics and methadone treatment centers where serological testing should have been made, but not HCV RNA to confirm hepatitis C infection.

ii) a community-based support to improve referral to specific care for those with hepatitis C infection; iii) a HCV care system delivery integrated within the existing health system with a simplified treatment protocol taking into account PWIDs specificities such as frequent HIV co-infection and methadone treatment; iv) an optimized treatment adherence through a combination of health care therapeutic education and CBO support; v) an increase in harm reduction activities to encompass HCV risk transmission and to prevent HCV reinfection.

Secondary objectives are:

* to assess all steps of the hepatitis C cascade of care (Hepatitis C infection diagnosis; HCV care enrolment; HCV treatment initiation; HCV treatment success);

* to assess the occurrence of adverse events (death, morbidity) and drug-related side-effects;

* to evaluate adherence to HCV treatment;

* to determine factors associated with treatment failure defined by a positive HCV RNA 12 weeks after the end of HCV treatment;

* to estimate the reinfection rate at the end of the study and to identify risk factors of HCV reinfection;

* to project the impact and cost-effectiveness of the implemented HCV treatment intervention.

Study design : the effectiveness-implementation hybrid study type 1 design will simultaneously allow assessing the effectiveness of Direct-Acting Antivirals (DAA) care strategy among PWIDs in Vietnam, and the potential obstacles to widespread implementation.

The strategy of care includes a large community-based mass screening, a simplified treatment protocol based on a combination of DAAs, taking into account co-morbidities (addiction, HIV), physician training and important support of Community Based Organizations (CBO's) for linkage to care after screening, treatment adherence and prevention of reinfection after cure.

In addition, 2 others components are included in the study:

* A modeling exercise to assess the impact of the intervention at the population level,

* A cost-effectiveness analysis to further inform policy-makers.

Patients will be followed for 48 weeks after initiating HCV treatment. The estimated enrolment is 1050 participants.

Study population: people who currently inject drugs or who have recently started opioid substitution treatment.

Implementation: The study is linked to the NIDA RO1 DA041978 / ANRS 12353 DRIVE project. Participant recruitment will take place through DRIVE RDS survey and DRIVE cohort follow-up visit in two community sites managed by peer-groups in Hai Phong. All participants with positive HCV serology will be screened for hepatitis C and positive HCV RNA will be proposed for DAA treatment in 3 hospital-based HCV clinics. All participants will attend 9 study visits, comprising of clinical examination, blood collection for side effects and viral load assessment, therapeutic education, questionnaires on alcohol use, on sexual, drug use and other behaviors focusing on HCV infection risks or HCV reinfection risks and on quality of life, and harm reduction activities with the support of CBOs.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
979
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
All patientsSofosbuvir 400 mg and Daclatasvir 60 mgAll patients will receive sofosbuvir 400-mg and daclatasvir 60-mg (1 tablet each per day) during 12 weeks.
HIV/HCV co-infected patientsSofosbuvir 400 mg and Daclatasvir 90 mgFor HIV/HCV co-infected patients receiving efavirenz or nevirapine, daclatasvir dose will be increased to 90-mg per day (sofosbuvir 400 mg and daclatasvir 90 mg)
Cirrhosis with ribavirin contra-indicationSofosbuvir and Daclatasvir for 24 weeksIn case of cirrhosis with ribavirin contra-indication : sofosbuvir and daclatasvir for 24 weeks
CirrhosisRibavirinIn case of cirrhosis : ribavirin will be added to sofosbuvir / daclatasvir 12 weeks
Primary Outcome Measures
NameTimeMethod
Proportion of all patients in success of the model of careWeek 48

Proportion of patients with HCV RNA \< 15 IU/mL at the end of the study among patients who have signed the informed consent.

Secondary Outcome Measures
NameTimeMethod
Proportion of patients curedWeek 24

Number of patients with HCV RNA \< 15 IU/mL among those initiating the treatment eligible

Rate of mortalityWeek 48

Rate of deaths among all participants with hepatitis C infection

Factors associated with HCV treatment failureWeek 24

Socio-demographic, co-infection, virological, adherence, behavioral, psychiatric disorders, intervention contact, recent incarceration, homelessness factors

Rate of reinfectionWeek 48

Number of patients with HCV RNA ≥ 15 IU/mL at the end of the study among cured patients

Frequency, type and time to drug-related clinical or biological adverse reactionsWeek 48

All drug-related clinical or biological adverse reactions of grade 3 or 4 or leading to treatment interruption

Factors associated with HCV reinfectionWeek 48

Socio-demographic, co-infection, virological, adherence, behavioral, psychiatric disorders, intervention contact, recent incarceration, homelessness factors

Adherence assessmentWeek 12

Self-questionnaire on DAA drug intake and drug accountability for DAA

Proportion of patients enrolled in carePre-inclusion visit

Proportion of patients with HCV RNA \> 15 IU/mL who attended the pre inclusion visit at HCV clinic among those with hepatitis C infection;

Proportion of patients initiating DAA treatmentInitiation treatment visit

Proportion of patients who initiate the treatment among patients enrolled in care and eligible for treatment

Incremental cost-effectiveness ratio (ICER)Week 48

Estimation of the mean ICER which will be compared against standard thresholds for intervention's being cost-effective in LMIC settings

Proportion of patients with detectable HCV RNAScreening pre-inclusion

Proportion of patients with HCV RNA \> 15 IU/mL among those with positive HCV Ab

Frequency, type and time to grade 3 or 4 adverse clinical or biological events.Week 48

All adverse events will be graded according to the ANRS adverse events grading table

Effect of the HCV treatment interventionWeek 48

Estimation of the impact of the intervention on HCV infections and DALYs averted, QALYs saved, HCV incidence and prevalence as projected by the model under various scenarios

Trial Locations

Locations (2)

Hai Phong University of Medicine and Pharmacy

🇻🇳

Hai Phong, Vietnam

Viet Tiep Hospital

🇻🇳

Hải Phòng, Vietnam

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