Therapy for Hepatitis C Virus (HCV) in Primary Treatment Failure in Pakistan
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 318
- 试验地点
- 1
- 主要终点
- Determine sustained virological response rate (SVR)
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •APRI score - calculated from serum AST concentration in IU/L and platelet count /L (a result of ≥2 demonstrates presence of cirrhosis)
- •Liver transient elastography assessment (a 'Fibroscan'). A result of ≥12.5 kPa will demonstrate cirrhosis.
- •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.
排除标准
- •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
研究组 & 干预措施
12 weeks - treatment with sofosbuvir/velpatasvir (usual regime)
134 first-line treatment failure patients randomly allocated to receive 12 weeks treatment with sofosbuvir/velpatasvir. 1:1 random allocation with stratification for the presence of cirrhosis
干预措施: Epclusa (nucleotide HCV NS5B polymerase inhibitors). (Drug)
24 weeks - treatment with sofosbuvir/velpatasvir (intervention)
134 first-line treatment failure patients randomly allocated to receive 24 weeks treatment with sofosbuvir/velpatasvir. 1:1 random allocation with stratification for the presence of cirrhosis
干预措施: Epclusa (nucleotide HCV NS5B polymerase inhibitors). (Drug)
结局指标
主要结局
Determine sustained virological response rate (SVR)
时间窗: 36+/- 2 weeks from the point of randomisation
Sustained virological response (SVR) defined as proportion of patients who are HCV RNA negative with a sensitive molecular test (sensitivity \<100 IU/ml) 36 +/- 2 weeks from the time of randomisation. 2\. To determine the proportion of people with decompensated cirrhosis who achieve a sustained virological response (SVR) 36 weeks (+/-2 weeks) after first dose of medication (sofosbuvir/velpatasvir) administered.
次要结局
- Cost effectiveness of treatment(24 weeks after randomisation)
- Determine viral polymorphisms in HCV(12 months)
- Health care costs(24 weeks after randomisation)