Specialty: Hepatology, Primary sub-specialty: Hepatology
Conditions
Interventions
A total of 60 patients will be randomized (between weeks 8-12) to receive a total of 12 weeks of sofosbuvir/velpatasvir treatment (standard therapy) or 24 weeks of sofosbuvir/velpatasvir (extended th
Sponsors
Queen Mary University of London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Voluntarily signed informed consent form 2. Aged 18 years or older 3. Chronic HCV infection, defined by anti-HCV antibody or HCV RNA detection for greater than 6 months 4. Infected with genotype 3 HCV (identified by referring hospital) 5. Meets NHS England treatment criteria to commence sofosbuvir/velpatasvir 6. Pre-treatment HCV RNA >10,000 iu/mL (can be any time before treatment week 0) 7. HCV RNA > or equal to 30 iu/mL at treatment week 2 (+/- 3 days) 8. Has cirrhosis defined by: evidence of portal hypertension, OR APRI >2 plus AST:ALT ratio >1, OR radiological evidence of cirrhosis, OR fibroscan score >11.5kPa, OR liver biopsy showing cirrhosis 9. Patients with decompensated cirrhosis (variceal bleeding, ascites and encephalopathy) can be included 10. Patients with malignancy including hepatocellular carcinoma can be included 11. Patients with liver transplant can be included 12. Patients coinfected with chronic hepatitis B virus or human immunodeficiency virus can be included 13. Female subjects of childbearing potential must have documented negative pregnancy test prior to enrolment (negative urinary pregnancy test), and if engaged in heterosexual intercourse must use protocol specified method of contraception (see below) during study drug treatment and for 30 days after last dose 14. Male subjects engaged in heterosexual intercourse with a female of childbearing potential should protocol specified method of contraception during study drug treatment and for 30 days after last dose
Exclusion criteria
Exclusion criteria: 1. Any of the above inclusion criteria not met 2. Any of the following criteria excludes a subject from enrolling into this study 3. Clinically-significant medical or psychiatric illness (other than chronic HCV) in the past, present, or being evaluated, that may interfere with participant treatment, safety, assessment or compliance with the protocol. 4. Severe renal impairment with eGFR <30 mL/min/1.73m2 or requiring dialysis 5. Alcohol consumption or illicit drug abuse likely to interfere with participant treatment, safety, assessment or compliance with protocol, as deemed by the investigator 6. Previous exposure to sofosbuvir (or other NS5B inhibitor) or NS5A inhibitor 7. Severe allergy to study drugs, its metabolites or formulation excipient (see SmPC for details) 8. Any investigational medicinal product = 6 weeks prior to treatment start 9. Pregnant or nursing female, or males wishing to conceive during the period of study treatment + 30 days after 10. Patients who adhered to less than 90% of prescribed sofosbuvir/velpatasvir at screening 11. In accordance with the SmPC of sofosbuvir/velpatasvir concomitant use of the following medications are contraindicated: 11.1. Anticonvulsants - carbamazepine, phenytoin, phenobarbital, oxcarbazepine 11.2. Antimycobacterials – rifampicin, rifabutin, rifapentine 11.3. Antiretrovirals - efavirenz 11.4. St John’s wort 11.5. Modafinil 11.6. Proton-pump inhibitors should be avoided and if necessary, should be administered 4 hours after at maximum doses equivalent to 20mg omeprazole per day 11.7. Amiodarone should be avoided and if necessary, close monitoring is required 12. Using effective contraception if of child-bearing potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients in each group (12 or 24 weeks of sofosbuvir/velpatasvir) with undetectable HCV RNA (below limit of quantification up to 15 IU/mL) in serum at 12 weeks (+ 4 weeks) after end of treatment (SVR12). | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Proportion of patients in each group requiring premature treatment discontinuation, reported in patient notes, throughout the treatment period 2. Proportion of patients in each group who developed serious adverse events, reported in patient notes, throughout the trial period 3. Quality of life, measured as SF36 questionnaire scores, in each treatment group at end of study treatment and end of study follow-up (12 weeks post-treatment end) | — |
Countries
England, United Kingdom
Contacts
Public ContactMichelle;David Cheung;Lieberman
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Outcome results
None listed