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

Hepatitis C Clinical Trial

— DRIVE-C  

Official title:

Towards HCV Elimination: Evaluation of an Integrated Model of HCV Care Targeting People Who Inject Drugs in Hai Phong, Vietnam

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03537196
• Other study ID #: ANRS 12380 DRIVE-C
• Status: Completed
• Phase: Phase 4
• Start date: November 13, 2018
• Est. completion date: December 30, 2022

Study information

• Verified date: October 2023
• Source: ANRS, Emerging Infectious Diseases
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 979
• Est. completion date: December 30, 2022
• Est. primary completion date: November 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Drug Use
• Hepatitis
• Hepatitis A
• Hepatitis C
• Viral Hepatitis C

Intervention

Drug:
• Sofosbuvir 400 mg and Daclatasvir 60 mg
All patients will receive sofosbuvir 400-mg and daclatasvir 60-mg (1 tablet each per day) during 12 weeks.
• Sofosbuvir 400 mg and Daclatasvir 90 mg
For HIV/HCV co-infected patients receiving efavirenz or nevirapine, daclatasvir dose will be increased to 90-mg per day.
• Ribavirin
In case of cirrhosis: Ribavirin will be added to sofosbuvir/daclatasvir during the 12 weeks of treatment. The dose will be adapted to the patient weight although the vast majority of patients (weight < 75 kg) will receive 500 mg x 2/day. In case of ribavirin contra-indication or side effects leading to ribavirin discontinuation, sofosbuvir/daclatasvir will be used 24 weeks.
• Sofosbuvir and Daclatasvir for 24 weeks
In case of cirrhose and of ribavirin contra-indication or side effects leading to ribavirin discontinuation, sofosbuvir/daclatasvir will be used 24 weeks.

Locations

Country	Name	City	State
Vietnam	Viet Tiep Hospital	H?i Phòng
Vietnam	Hai Phong University of Medicine and Pharmacy	Hai Phong

Sponsors (1)

Lead Sponsor	Collaborator
ANRS, Emerging Infectious Diseases

Country where clinical trial is conducted

Vietnam, 

References & Publications (22)

Altice FL, Azbel L, Stone J, Brooks-Pollock E, Smyrnov P, Dvoriak S, Taxman FS, El-Bassel N, Martin NK, Booth R, Stover H, Dolan K, Vickerman P. The perfect storm: incarceration and the high-risk environment perpetuating transmission of HIV, hepatitis C virus, and tuberculosis in Eastern Europe and Central Asia. Lancet. 2016 Sep 17;388(10050):1228-48. doi: 10.1016/S0140-6736(16)30856-X. Epub 2016 Jul 14. — View Citation

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Clatts MC, Colon-Lopez V, Giang LM, Goldsamt LA. Prevalence and incidence of HCV infection among Vietnam heroin users with recent onset of injection. J Urban Health. 2010 Mar;87(2):278-291. doi: 10.1007/s11524-009-9417-9. — View Citation

Conti F, Buonfiglioli F, Scuteri A, Crespi C, Bolondi L, Caraceni P, Foschi FG, Lenzi M, Mazzella G, Verucchi G, Andreone P, Brillanti S. Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals. J Hepatol. 2016 Oct;65(4):727-733. doi: 10.1016/j.jhep.2016.06.015. Epub 2016 Jun 24. — View Citation

Des Jarlais D, Duong HT, Pham Minh K, Khuat OH, Nham TT, Arasteh K, Feelemyer J, Heckathorn DD, Peries M, Moles JP, Laureillard D, Nagot N; (The Drive Study Team). Integrated respondent-driven sampling and peer support for persons who inject drugs in Haiphong, Vietnam: a case study with implications for interventions. AIDS Care. 2016 Oct;28(10):1312-5. doi: 10.1080/09540121.2016.1178698. Epub 2016 May 13. — View Citation

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. EASL Recommendations on Treatment of Hepatitis C 2016. J Hepatol. 2017 Jan;66(1):153-194. doi: 10.1016/j.jhep.2016.09.001. Epub 2016 Sep 22. No abstract available. — View Citation

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Grebely J, Matthews GV, Lloyd AR, Dore GJ. Elimination of hepatitis C virus infection among people who inject drugs through treatment as prevention: feasibility and future requirements. Clin Infect Dis. 2013 Oct;57(7):1014-20. doi: 10.1093/cid/cit377. Epub 2013 May 31. — View Citation

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Pawlotsky JM, Feld JJ, Zeuzem S, Hoofnagle JH. From non-A, non-B hepatitis to hepatitis C virus cure. J Hepatol. 2015 Apr;62(1 Suppl):S87-99. doi: 10.1016/j.jhep.2015.02.006. — View Citation

Pham DA, Leuangwutiwong P, Jittmittraphap A, Luplertlop N, Bach HK, Akkarathamrongsin S, Theamboonlers A, Poovorawan Y. High prevalence of Hepatitis C virus genotype 6 in Vietnam. Asian Pac J Allergy Immunol. 2009 Jun-Sep;27(2-3):153-60. — View Citation

Sereno L, Mesquita F, Kato M, Jacka D, Nguyen TT, Nguyen TN. Epidemiology, responses, and way forward: the silent epidemic of viral hepatitis and HIV coinfection in Vietnam. J Int Assoc Physicians AIDS Care (Chic). 2012 Sep-Oct;11(5):311-20. doi: 10.1177/1545109712453939. Epub 2012 Jul 24. — View Citation

Smith DJ, Combellick J, Jordan AE, Hagan H. Hepatitis C virus (HCV) disease progression in people who inject drugs (PWID): A systematic review and meta-analysis. Int J Drug Policy. 2015 Oct;26(10):911-21. doi: 10.1016/j.drugpo.2015.07.004. Epub 2015 Jul 26. — View Citation

Tanimoto T, Nguyen HC, Ishizaki A, Chung PT, Hoang TT, Nguyen VT, Kageyama S, Oka S, Pham VT, Ichimura H. Multiple routes of hepatitis C virus transmission among injection drug users in Hai Phong, Northern Vietnam. J Med Virol. 2010 Aug;82(8):1355-63. doi: 10.1002/jmv.21787. — View Citation

Vickerman P, Martin N, Turner K, Hickman M. Can needle and syringe programmes and opiate substitution therapy achieve substantial reductions in hepatitis C virus prevalence? Model projections for different epidemic settings. Addiction. 2012 Nov;107(11):1984-95. doi: 10.1111/j.1360-0443.2012.03932.x. Epub 2012 Jul 12. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of all patients in success of the model of care	Proportion of patients with HCV RNA < 15 IU/mL at the end of the study among patients who have signed the informed consent.	Week 48
Secondary	Proportion of patients with detectable HCV RNA	Proportion of patients with HCV RNA > 15 IU/mL among those with positive HCV Ab	Screening pre-inclusion
Secondary	Proportion of patients enrolled in care	Proportion of patients with HCV RNA > 15 IU/mL who attended the pre inclusion visit at HCV clinic among those with hepatitis C infection;	Pre-inclusion visit
Secondary	Proportion of patients initiating DAA treatment	Proportion of patients who initiate the treatment among patients enrolled in care and eligible for treatment	Initiation treatment visit
Secondary	Proportion of patients cured	Number of patients with HCV RNA < 15 IU/mL among those initiating the treatment eligible	Week 24
Secondary	Rate of reinfection	Number of patients with HCV RNA = 15 IU/mL at the end of the study among cured patients	Week 48
Secondary	Rate of mortality	Rate of deaths among all participants with hepatitis C infection	Week 48
Secondary	Frequency, type and time to grade 3 or 4 adverse clinical or biological events.	All adverse events will be graded according to the ANRS adverse events grading table	Week 48
Secondary	Frequency, type and time to drug-related clinical or biological adverse reactions	All drug-related clinical or biological adverse reactions of grade 3 or 4 or leading to treatment interruption	Week 48
Secondary	Adherence assessment	Self-questionnaire on DAA drug intake and drug accountability for DAA	Week 12
Secondary	Factors associated with HCV treatment failure	Socio-demographic, co-infection, virological, adherence, behavioral, psychiatric disorders, intervention contact, recent incarceration, homelessness factors	Week 24
Secondary	Factors associated with HCV reinfection	Socio-demographic, co-infection, virological, adherence, behavioral, psychiatric disorders, intervention contact, recent incarceration, homelessness factors	Week 48
Secondary	Effect of the HCV treatment intervention	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	Week 48
Secondary	Incremental cost-effectiveness ratio (ICER)	Estimation of the mean ICER which will be compared against standard thresholds for intervention's being cost-effective in LMIC settings	Week 48