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

Hepatitis C Clinical Trial

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

Status Enrolling by invitation

Clinical Trial 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.

Clinical Trial Description

Chronic infection with the hepatitis C virus (HCV) causes liver damage and, in many, liver cancer. We have effective drugs allowing us to cure most infected people and this stops the liver becoming damaged. Hepatitis C is common in Pakistan and the government is planning a massive national program to find and treat everyone who is infected. The government funded treatment program will fund therapy and assumes that the drugs will cure the vast majority of infected people and hence, in line with international recommendations, they are not planning to evaluate treatment outcomes. The efficacy of the drugs used in Pakistan (sofosbuvir plus daclatasvir) have not been widely assessed in the Pakistani population and their efficacy is not yet proven. In a separate protocol the efficacy of first line therapy in Pakistan will be determined and this study will examine the optimal management for people who have not responded.

This trial will determine optimal treatment regimens in resource poor settings by comparing two affordable, readily available treatment options. 268 patients who meet the inclusion criteria and who accept participation will be enrolled. These patients will be randomly allocated to two equal sized groups (134 per group) and allocated 1:1 (stratified by the presence or absence of cirrhosis) to receive: i) 12 weeks treatment with sofosbuvir/velpatasvir or ii) 24 weeks treatment with sofosbuvir/velpatasvir. An additional 50 patients with decompensated cirrhosis will form a third observational group iii) who will receive 24 weeks of sofosbuvir/velpatasvir. Patients will be assessed for sustained virological response (SVR) from the point of randomisation at 12 (+/-1 week) and 24 weeks (+/-1 week) and then finally at 36 weeks (+/-2 weeks).

The study outline is as follows:

1) HCV patients who fail to respond to the first-line therapy regime will be identified via sustained virological response (SVR) assessment 12 weeks (range 11-18 weeks) after completion of a course of all oral antiviral therapy with sofosbuvir plus daclatasvir for either 12 or 24 weeks with or without ribavirin provided by a recognized provider of health care in Pakistan.

• Potential participants who have been invited to participate will have a member of the medical team explain the details of the trial, they will then be given a maximum of 24h to read the relevant information sheets and to speak to a clinical member of the study team to ask any further questions, before they commence the process of fully informed consent.

• After obtaining written informed consent, a study specific participant identification number (ID) will be assigned to the participant.

• Consenting patients will have venepuncture performed as per the site's standard operating procedure (SOP). The donated pre-treatment plasma sample will be retained

• Once enrolled, the 268 patients accepted into the study will be randomly allocated into two groups (134 patients per group) using a computerised 1:1 randomisation programme (stratified by the presence or absence of decompensated cirrhosis) to receive:

i) sofosbuvir(400mg/day)/velpatasvir (100mg/day) - 12 weeks ii) sofosbuvir(400mg/day)/velpatasvir (100mg/day) - 24 weeks

• The third observational group of decompensated patients (up to 50 patients) will be given sofosbuvir (400mg/day)/velpatasvir (100mg/day) - 24 weeks

• All patients will be treated for either 12 or 24 weeks.

• Each patient will be reviewed at weeks: 4 (+/- 1 week), 12 (+/-1 week), 24 (+/-1 week) and 36 ((+/- 2 week) after the first dose of second-line treatment (randomisation).

• Patients with second-line treatment failure will have 10ml blood sample taken for viral sequencing.

• Data will be collected on paper case report forms (CRFs) which will be securely stored prior to the data being transferred to a secure on-line database. Paper records will be retained as primary source documents.

• Cost effectiveness of the treatment regimens will be measured from the Pakistan health service perspective. Costings for the drugs, clinic, laboratory testing, staff and facility costs associated with each treatment regimen per patient will be calculated. ;

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

• NCT number: NCT05248919
• Study type: Interventional
• Source: Queen Mary University of London
• Status: Enrolling by invitation
• Phase: N/A
• Start date: June 1, 2023
• Completion date: December 2024