Therapy for Hepatitis C Virus (HCV) in Primary Treatment Failure in Pakistan

• Status: Recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This trial is linked to a largescale observational study determining the efficacy of sofosbuvir/daclatasvir in people in Pakistan (involving a separate protocol). The observational study will identify a cohort of patients who have not responded to first-line antiviral therapy (sofosbuvir plus daclatasvir) and the optimal treatment for these patients is unclear. This trial will address this issue by comparing two second-line treatment regimens to determine the preferred treatment option.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Queen Mary University of London
• Collaborators: Aga Khan University; Bristol University; Dow University, Pakistan; University of Oxford

Criteria

Inclusion Criteria:

• Willing and able to give written informed consent or sign consent forms with a fingerprint.

• Male or female, age ≥ 18 years.

• Willing to comply with study procedures

• Resident in the area and not planning to leave the region.

• Have a confirmed diagnosis at the time of screening of active hepatitis C infection - defined as detectable HCV RNA using a molecular diagnostic assay with a sensitivity of >100IU/ml OR detectable HCV Core antigen using an assay with a sensitivity of >1.5 pg/ml.

• Treatment experience within the last 24 months of antiviral therapy drugs recommended by the government program and administered in line with national recommendations. The current recommendations are that patients without cirrhosis should receive sofosbuvir 400 mg per day in combination with daclatasvir 60 mg per day for a total of 12 weeks and for patients with cirrhosis therapy should involve sofosbuvir 400 mg per day in combination with daclatasvir 60 mg per day for a total of 24 weeks. Patients who receive additional medication (including ribavirin) can be enrolled in the study but the additional medication should be noted.

• The subject's medical records must include sufficient detail of prior treatment to confirm eligibility.

• Have a stored sample of serum or plasma that is known to contain detectable HCV RNA and which can be made available to the study team or be willing to provide such a sample

• Have undergone, or be willing to undergo, an approved screening test for determining liver cirrhosis either by:

1. APRI score - calculated from serum AST concentration in IU/L and platelet count /L (a result of ≥2 demonstrates presence of cirrhosis)

2. Liver transient elastography assessment (a 'Fibroscan'). A result of ≥12.5 kPa will demonstrate cirrhosis.

3. liver biopsy within 1 year of screening

• Females of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day 1 prior to enrolment.

• Lactating females must agree to discontinue nursing before starting study drug.

• Subjects must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments.

Exclusion Criteria:

• Unwilling or unable to give consent

• Clinically significant illness (other than HCV) or other major medical condition that may interfere with the subject's treatment, assessment or compliance with protocol.

• History of discontinuation the most recent regime due to an adverse event

• Co-morbidities limiting life expectancy to less than 12 months

• Gastrointestinal disorder that could interfere with the absorption of the study drugs

• Significant cardiac disease

• Unstable psychiatric condition

• Significant drug allergy (e.g. hepatotoxicity)

• Infection with hepatitis B virus (HBV) or Human immunodeficiency virus (HIV)

• Unable or unwilling to undergo the necessary procedures - undergoing blood testing and ultrasound/fibroscan scanning.

• Previous poor compliance with medication (defined as failure to take >80% of the prescribed medication)

• Have undergone liver or other solid organ transplantation

• Have a current or recent diagnosis of hepatocellular carcinoma or any other malignancy