Treating Hepatitis C in Pakistan. Strategies to Avoid Resistance to Antiviral Drugs

NCT04943588 | Recruiting DMC

• 1 other identifier: PakHepCscreen
• Study Type: observational
• Target: 25,000
• Locations: 1 country
• Sites: 1

Brief Summary

We will determine how best to manage the hepatitis C virus (HCV) epidemic in Pakistan by measuring effectiveness of Pakistan-government sponsored current therapies, emergence of viral resistance, consequences of infection (chiefly liver cancer) and through developing models, based on incidence data, determine the proportion of people who need curative treatment to eliminate HCV, and assess whether targeting can optimise this.

Conditions

Hepatitis C, Chronic

Outcome Measures

Primary Outcomes (3)

• SVR

  After first-line treatment, SVR will be measured to record treatment failure or success

  12 weeks after treatment completion

• Incidence of new infections

  Measure HCV antibodies in people who initially tested HCV antibody negative at screening.

  12 months after screening

• Incidence of re-infection

  In patients who achieved an SVR after first-line treatment will then be tested for HCV core antigen over 12 months.

  12 months after first SVR test.

Secondary Outcomes (5)

• Health related Quality of Life

  Screening stage

• Health care costs and productivity assessment associated with HCV infection

  screening stage

• Risk assessment

  12 months

• Viral polymorphisms in HCV

  2 years

• Viral polymorphisms in HCV associated with hepatocellular carcinoma

  4 years

Study Arms (4)

HCV Negative

At initial screen, this population will be HCV negative via the diagnostic testing. They will be eligible if they fulfil the following: 1. over 18 yrs old. 2. willing to participate 3. no previous history of therapy with oral medication for chronic HCV infection

Diagnostic Test: HCV Antibody test (Point of care)

HCV Positive with first-line treatment success

At the initial screen, this population (approx. 5000) will be HCV RNA positive and will undergo 12/24 week treatment of sofosbuvir plus daclatasvir. After treatment, their blood sample will show that they have achieved a sustained virological response (SVR) defined as HCV RNA undetectable.

Diagnostic Test: HCV RNA (PCR)

HCV positive with first-line treatment failure

At the initial screen, this population (approx. 5000) will be HCV RNA positive and will undergo 12/24 week treatment of sofosbuvir/daclatasvir. After treatment, this proportion of people will NOT achieve an (SVR - defined as HCV RNA undetectable).

Diagnostic Test: HCV RNA (PCR)

Cirrhotic Patients

Hepatitis C RNA positive that have cirrhosis

Diagnostic Test: AST/ALT and platelets measurement

Interventions

HCV RNA (PCR) DIAGNOSTIC_TEST

We will test HCV positive patients after treatment to observe if they achieve SVR

HCV Positive with first-line treatment success; HCV positive with first-line treatment failure

HCV Antibody test (Point of care) DIAGNOSTIC_TEST

HCV antibody test used to establish if patients have had or are actively infected with HCV

HCV Negative

AST/ALT and platelets measurement DIAGNOSTIC_TEST

AST/ALT and platelets to determine APRI score

Cirrhotic Patients

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Recruitment of uninfected and infected people will be from two provinces in Pakistan (Sindh and Punjab) where there is a high prevalence of HCV. Recruitment will reflect the community sample.

You may qualify if:

• Adults over 18yrs old
• Willing to undergo hepatitis C testing
• Able and willing to give informed consent
• Willing to return in 12 months time for repeat testing
• Resident in area and not planning to leave the region

You may not qualify if:

• Unwilling to give consent
• Unwilling or unable to undergo the necessary procedures
• Clinically significant illness (other than HCV) or other major medical condition that may interfere with the subject's treatment, assessment or compliance with protocol.
• Co-morbidities limiting life expectancy to less than 12 months

Sponsors & Collaborators

• Queen Mary University of London: lead
• Aga Khan University: collaborator
• Dow University of Health Sciences: collaborator
• University of Oxford: collaborator
• University of Bristol: collaborator

Study Sites (1)

Aga Khan University

Karachi, Pakistan

RECRUITING

Related Publications (9)

• El-Akel W, El-Sayed MH, El Kassas M, El-Serafy M, Khairy M, Elsaeed K, Kabil K, Hassany M, Shawky A, Yosry A, Shaker MK, ElShazly Y, Waked I, Esmat G, Doss W. National treatment programme of hepatitis C in Egypt: Hepatitis C virus model of care. J Viral Hepat. 2017 Apr;24(4):262-267. doi: 10.1111/jvh.12668. Epub 2017 Feb 1.

  PMID: 28145032 RESULT

• Smith D, Magri A, Bonsall D, Ip CLC, Trebes A, Brown A, Piazza P, Bowden R, Nguyen D, Ansari MA, Simmonds P, Barnes E; STOP-HCV Consortium. Resistance analysis of genotype 3 hepatitis C virus indicates subtypes inherently resistant to nonstructural protein 5A inhibitors. Hepatology. 2019 May;69(5):1861-1872. doi: 10.1002/hep.29837. Epub 2018 Apr 27.

  PMID: 29425396 RESULT

• Zeuzem S, Foster GR, Wang S, Asatryan A, Gane E, Feld JJ, Asselah T, Bourliere M, Ruane PJ, Wedemeyer H, Pol S, Flisiak R, Poordad F, Chuang WL, Stedman CA, Flamm S, Kwo P, Dore GJ, Sepulveda-Arzola G, Roberts SK, Soto-Malave R, Kaita K, Puoti M, Vierling J, Tam E, Vargas HE, Bruck R, Fuster F, Paik SW, Felizarta F, Kort J, Fu B, Liu R, Ng TI, Pilot-Matias T, Lin CW, Trinh R, Mensa FJ. Glecaprevir-Pibrentasvir for 8 or 12 Weeks in HCV Genotype 1 or 3 Infection. N Engl J Med. 2018 Jan 25;378(4):354-369. doi: 10.1056/NEJMoa1702417.

  PMID: 29365309 RESULT

• Lim AG, Walker JG, Mafirakureva N, Khalid GG, Qureshi H, Mahmood H, Trickey A, Fraser H, Aslam K, Falq G, Fortas C, Zahid H, Naveed A, Auat R, Saeed Q, Davies CF, Mukandavire C, Glass N, Maman D, Martin NK, Hickman M, May MT, Hamid S, Loarec A, Averhoff F, Vickerman P. Effects and cost of different strategies to eliminate hepatitis C virus transmission in Pakistan: a modelling analysis. Lancet Glob Health. 2020 Mar;8(3):e440-e450. doi: 10.1016/S2214-109X(20)30003-6.

  PMID: 32087176 RESULT

• Foster GR, Afdhal N, Roberts SK, Brau N, Gane EJ, Pianko S, Lawitz E, Thompson A, Shiffman ML, Cooper C, Towner WJ, Conway B, Ruane P, Bourliere M, Asselah T, Berg T, Zeuzem S, Rosenberg W, Agarwal K, Stedman CA, Mo H, Dvory-Sobol H, Han L, Wang J, McNally J, Osinusi A, Brainard DM, McHutchison JG, Mazzotta F, Tran TT, Gordon SC, Patel K, Reau N, Mangia A, Sulkowski M; ASTRAL-2 Investigators; ASTRAL-3 Investigators. Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection. N Engl J Med. 2015 Dec 31;373(27):2608-17. doi: 10.1056/NEJMoa1512612. Epub 2015 Nov 17.

  PMID: 26575258 RESULT

• Wing PAC, Jones M, Cheung M, DaSilva S, Bamford C, Jason Lee WY, Aranday-Cortes E, Da Silva Filipe A, McLauchlan J, Smith D, Irving W, Cunningham M, Ansari A, Barnes E, Foster GR. Amino Acid Substitutions in Genotype 3a Hepatitis C Virus Polymerase Protein Affect Responses to Sofosbuvir. Gastroenterology. 2019 Sep;157(3):692-704.e9. doi: 10.1053/j.gastro.2019.05.007. Epub 2019 May 10.

  PMID: 31078622 RESULT

• Huang R, Rao H, Xie Q, Gao Z, Li W, Jiang D, Mo H, Massetto B, Stamm LM, Brainard DM, Wei L. Comparison of the efficacy of sofosbuvir plus ribavirin in Chinese patients with genotype 3a or 3b HCV infection. J Med Virol. 2019 Jul;91(7):1313-1318. doi: 10.1002/jmv.25454. Epub 2019 Apr 3.

  PMID: 30861150 RESULT

• Lim AG, Qureshi H, Mahmood H, Hamid S, Davies CF, Trickey A, Glass N, Saeed Q, Fraser H, Walker JG, Mukandavire C, Hickman M, Martin NK, May MT, Averhoff F, Vickerman P. Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination. Int J Epidemiol. 2018 Apr 1;47(2):550-560. doi: 10.1093/ije/dyx270.

  PMID: 29309592 RESULT

• Arif A, Hasnain A, Chaudhry A, Asim M, Shafqat MN, Altaf A, Saba N, Kemos P, Ansari MA, Barnes E, Metcalfe C, Vickerman P, Qureshi H, Hamid S, Choudhry AA, Niaz SK, Foster GR, Choudhry N. HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol. BMC Public Health. 2023 Dec 18;23(1):2529. doi: 10.1186/s12889-023-17290-3.

  PMID: 38110885 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

We will take Blood samples to test presence of Hepatitis C RNA only.

MeSH Terms

Conditions

Hepatitis C, Chronic

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Graham R Foster, MBBS

  Queen Mary University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Graham R Foster, MBBS

CONTACT

07968836267; g.r.foster@qmul.ac.uk

Naheed Choudhry, Phd

CONTACT

07951160549; naheedchoudhry1@gmail.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Project Manager

Study Record Dates

• First Submitted: June 21, 2021
• First Posted: June 29, 2021
• Study Start: November 1, 2021
• Primary Completion: January 30, 2026
• Study Completion: January 30, 2026
• Last Updated: March 24, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)