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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03537196
Other study ID # ANRS 12380 DRIVE-C
Secondary ID
Status Completed
Phase Phase 4
First received
Last updated
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
Health authority
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;

Study Design


Related Conditions & MeSH terms


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

Bruggmann P, Grebely J. Prevention, treatment and care of hepatitis C virus infection among people who inject drugs. Int J Drug Policy. 2015 Feb;26 Suppl 1:S22-6. doi: 10.1016/j.drugpo.2014.08.014. Epub 2014 Aug 30. — View Citation

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

Gish RG, Bui TD, Nguyen CT, Nguyen DT, Tran HV, Tran DM, Trinh HN; International Group for Liver Health in Viet Nam. Liver disease in Viet Nam: screening, surveillance, management and education: a 5-year plan and call to action. J Gastroenterol Hepatol. 2012 Feb;27(2):238-47. doi: 10.1111/j.1440-1746.2011.06974.x. — View Citation

Gower E, Estes C, Blach S, Razavi-Shearer K, Razavi H. Global epidemiology and genotype distribution of the hepatitis C virus infection. J Hepatol. 2014 Nov;61(1 Suppl):S45-57. doi: 10.1016/j.jhep.2014.07.027. Epub 2014 Jul 30. — View Citation

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

Guidelines for the Screening Care and Treatment of Persons with Chronic Hepatitis C Infection: Updated Version. Geneva: World Health Organization; 2016 Apr. Available from http://www.ncbi.nlm.nih.gov/books/NBK362924/ — View Citation

Kallman JB, Tran S, Arsalla A, Haddad D, Stepanova M, Fang Y, Wrobel VJ, Srishord M, Younossi ZM. Vietnamese community screening for hepatitis B virus and hepatitis C virus. J Viral Hepat. 2011 Jan;18(1):70-6. doi: 10.1111/j.1365-2893.2010.01278.x. — View Citation

Liang TJ, Ghany MG. Current and future therapies for hepatitis C virus infection. N Engl J Med. 2013 May 16;368(20):1907-17. doi: 10.1056/NEJMra1213651. — View Citation

Martin NK, Hickman M, Hutchinson SJ, Goldberg DJ, Vickerman P. Combination interventions to prevent HCV transmission among people who inject drugs: modeling the impact of antiviral treatment, needle and syringe programs, and opiate substitution therapy. Clin Infect Dis. 2013 Aug;57 Suppl 2(Suppl 2):S39-45. doi: 10.1093/cid/cit296. Erratum In: Clin Infect Dis. 2014 Apr;58(8):1203. — View Citation

Martin NK, Vickerman P, Grebely J, Hellard M, Hutchinson SJ, Lima VD, Foster GR, Dillon JF, Goldberg DJ, Dore GJ, Hickman M. Hepatitis C virus treatment for prevention among people who inject drugs: Modeling treatment scale-up in the age of direct-acting antivirals. Hepatology. 2013 Nov;58(5):1598-609. doi: 10.1002/hep.26431. Epub 2013 Aug 26. — View Citation

Mohd Hanafiah K, Groeger J, Flaxman AD, Wiersma ST. Global epidemiology of hepatitis C virus infection: new estimates of age-specific antibody to HCV seroprevalence. Hepatology. 2013 Apr;57(4):1333-42. doi: 10.1002/hep.26141. Epub 2013 Feb 4. — View Citation

Nguyen Truong T, Laureillard D, Lacombe K, Duong Thi H, Pham Thi Hanh P, Truong Thi Xuan L, Chu Thi N, Luong Que A, Vu Hai V, Nagot N, Tuaillon E, Dominguez S, Lemoine M. High Proportion of HIV-HCV Coinfected Patients with Advanced Liver Fibrosis Requiring Hepatitis C Treatment in Haiphong, Northern Vietnam (ANRS 12262). PLoS One. 2016 May 5;11(5):e0153744. doi: 10.1371/journal.pone.0153744. eCollection 2016. — View Citation

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 allClick 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
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