Clinical trial NCT03537196: DRug Use & Infections in ViEtnam - Hepatitis C (DRIVE-C)
Official title: Towards HCV Elimination: Evaluation of an Integrated Model of HCV Care Targeting People Who Inject Drugs in Hai Phong, Vietnam
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C
Drug Use
Viral Hepatitis C
Keywords: People who inject drugs
Hepatitis C
Direct Acting Antiviral
HCV Elimination
Vietnam
Viral hepatitis C
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
First posted: 2018-05-25
Enrollment: 979
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: All patients with detectable HCV RNA, eligible for treatment, will receive Direct Acting Antiviral drugs.
Primary purpose: TREATMENT

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.

Eligibility criteria: INCLUSION CRITERIA

* Participants of the ANRS 12353/NIDA ROI DA 041978 DRIVE study (age \> 18 years; positive urine test for heroin an/o methamphetamine \& skin marks of injection ) who either participated to the DRIVE RDS3 survey, or to the HIV-positive and HIV-negative DRIVE cohorts;
* Hepatitis C infection defined by a positive HCV RNA
* Signed informed consent form

EXCLUSION CRITERIA

* Severe associated diseases requiring specific treatment (including all specific AIDS defining illnesses, any severe sepsis, severe decompensated cirrhosis, suspicion of hepatocellular carcinoma);
* Any condition which might, in the investigator's opinion, compromise the safety of the patient by participating in the study including very severe clinical condition;
* Previous history of DAA use;
* Contraindication for treatment with sofosbuvir or daclatasvir;
* For women of childbearing potential i.e. women of childbearing age who are not menopausal, or permanently sterilized or not refraining from sexual activity:
* Pregnancy and breastfeeding
* Refusal to use a contraceptive method
* Renal failure with creatinine clearance ≤ 30 milliliter per minute;
* Person deprived of freedom by a judicial or administrative decision;
* Person who plan to move out from Hai Phong in the next 12 months;
* Person unable to understand the study;

Primary outcomes:
measure: Proportion of all patients in success of the model of care
timeFrame: Week 48
Secondary outcomes:
measure: Proportion of patients with detectable HCV RNA
timeFrame: Screening pre-inclusion
measure: Proportion of patients enrolled in care
timeFrame: Pre-inclusion visit
measure: Proportion of patients initiating DAA treatment
timeFrame: Initiation treatment visit
measure: Proportion of patients cured
timeFrame: Week 24
measure: Rate of reinfection
timeFrame: Week 48
measure: Rate of mortality
timeFrame: Week 48
measure: Frequency, type and time to grade 3 or 4 adverse clinical or biological events.
timeFrame: Week 48
measure: Frequency, type and time to drug-related clinical or biological adverse reactions
timeFrame: Week 48
measure: Adherence assessment
timeFrame: Week 12
measure: Factors associated with HCV treatment failure
timeFrame: Week 24
measure: Factors associated with HCV reinfection
timeFrame: Week 48
measure: Effect of the HCV treatment intervention
timeFrame: Week 48
measure: Incremental cost-effectiveness ratio (ICER)
timeFrame: Week 48
Other outcomes:
Locations:
city: Hai Phong
country: Vietnam
facility: Hai Phong University of Medicine and Pharmacy
city: Hải Phòng
country: Vietnam
facility: Viet Tiep Hospital
Study officials:
affiliation: Hai Phong University of Medicine and Pharmacy, Vietnam
name: KHUE M. PHAM, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nîmes University Hospital, France
name: DIDIER LAUREILLARD, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pathogenesis and Control of Chronic Infections (PCCI) UMR 1058 - INSERM, Univ Montpellier, EFS, Montpellier, France
name: NICOLAS NAGOT, MD, PhD
role: STUDY_DIRECTOR
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