Impact of Antiviral Therapy on Gastroesophageal Varices.

Completed

• Conditions: Chronic Hepatitis C; Cirrhosis
• Interventions: Drug: Pegylated interferon alfa-2a + Ribavirin; Drug: Pegylated interferon alfa-2a + Ribavirin + Boceprevir; Drug: Ledipasvir/Sofosbuvir; Drug: Pegylated interferon alfa-2a + Ribavirin +Telaprevir; Drug: Ombitasvir/paritaprevir/ritonavir+Dasabuvir; Drug: Daclatasvir+Sofosbuvir; Drug: Simeprevir+Sofosbuvir

• Registration Number: NCT02758509
• Lead Sponsor: Parc de Salut Mar

Brief Summary

Hepatitis C virus (HCV) chronic infection affects 200 million people worldwide. HCV antiviral treatment has evolved rapidly since 2011. The use of pegylated interferon (PEG-INF) with ribavirin (RBV) has supposed high serious adverse events (SAEs) and low efficacy, especially in patients with cirrhosis. The introduction of 1st generation protease inhibitors (PIs) in genotype-1 (GT1) HCV, such as boceprevir (BOC) and telaprevir (TVR), improved the efficacy but increased the SAEs. Currently, interferon-free direct-acting antivirals (IF-DAAs) achieve great effectiveness with minimum SAEs. However, studies evaluating efficacy and safety of DAAs in cirrhotic patients are limited in real clinical practice. The aim of our study is to evaluate in HCV-cirrhotic patients the efficacy and safety of 3 treatment strategies (PEG-IFN/RBV, PEG-IFN/RBV/PIs, and IF-DAAs) in routine practice according to European guidelines from 2010 to 2015. The secondary aim is to evaluate the impact of sustained virological response on gastroesophageal varices (GOV).

Detailed Description

Not available

Study Timeline

• Study Start: 2010-01-01
• Study First Submitted: 2016-04-26
• Study First Submitted QC: 2016-04-29
• Study First Posted: 2016-05-02
• Primary Completion: 2017-06-15
• Study Completion: 2017-10-15
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-18
• Last Update Posted: 2018-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 237

Inclusion Criteria

• Age ≥ 18 years.
• Signed informed consent.
• Chronic hepatitis C (anti-HCV antibodies and detectable HCV-RNA).
• Liver cirrhosis (transient elastography ≥ 14 kPa).
• Baseline upper gastrointestinal endoscopy to assess gastroesophageal varices

Exclusion Criteria

• Negative to provide signed informed consent.
• Negative to perform gastrointestinal endoscopy

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
PEG/RBV	Pegylated interferon alfa-2a + Ribavirin	Pegylated interferon alfa-2a 180 microg/week plus ribavirin 800-1200 mg during 48 weeks according to routine practice and European Guidelines (EASL recommendations 2011)
PEG/RBV+BOC or TVR	Pegylated interferon alfa-2a + Ribavirin + Boceprevir	Boceprevir 800 mg/8h or Telaprevir 750 mg/8h plus Pegylated interferon alfa-2a 180 microg/week plus ribavirin 800-1200 mg during 48 weeks according to routine practice and European Guidelines (EASL recommendations 2014)
PEG/RBV+BOC or TVR	Pegylated interferon alfa-2a + Ribavirin +Telaprevir	Boceprevir 800 mg/8h or Telaprevir 750 mg/8h plus Pegylated interferon alfa-2a 180 microg/week plus ribavirin 800-1200 mg during 48 weeks according to routine practice and European Guidelines (EASL recommendations 2014)
IF-DAAs	Ledipasvir/Sofosbuvir	Interferon-free direct-acting antiviral combinations according to routine practice and European Guidelines (EASL recommendations 2015) * Fixed-dose combination of sofosbuvir (400 mg) and ledipasvir (90 mg) daily +/- ribavirin 12-24 weeks * Fixed-dose combination of ombitasvir (75 mg), paritaprevir (12.5 mg) and ritonavir (50 mg) in one single tablet (two tablets once daily) and dasabuvir (250 mg) (one tablet twice daily) with ribavirin 800-1200 mg 12 weeks (Genotype 1b) or 24 weeks (genotype 1a) * Daily sofosbuvir (400 mg) and daily simeprevir (150 mg) +/- ribavirin 12-24 weeks * Daily sofosbuvir (400 mg) and daily daclatasvir (60 mg) +/- ribavirin 12-24 weeks
IF-DAAs	Ombitasvir/paritaprevir/ritonavir+Dasabuvir	Interferon-free direct-acting antiviral combinations according to routine practice and European Guidelines (EASL recommendations 2015) * Fixed-dose combination of sofosbuvir (400 mg) and ledipasvir (90 mg) daily +/- ribavirin 12-24 weeks * Fixed-dose combination of ombitasvir (75 mg), paritaprevir (12.5 mg) and ritonavir (50 mg) in one single tablet (two tablets once daily) and dasabuvir (250 mg) (one tablet twice daily) with ribavirin 800-1200 mg 12 weeks (Genotype 1b) or 24 weeks (genotype 1a) * Daily sofosbuvir (400 mg) and daily simeprevir (150 mg) +/- ribavirin 12-24 weeks * Daily sofosbuvir (400 mg) and daily daclatasvir (60 mg) +/- ribavirin 12-24 weeks
IF-DAAs	Daclatasvir+Sofosbuvir	Interferon-free direct-acting antiviral combinations according to routine practice and European Guidelines (EASL recommendations 2015) * Fixed-dose combination of sofosbuvir (400 mg) and ledipasvir (90 mg) daily +/- ribavirin 12-24 weeks * Fixed-dose combination of ombitasvir (75 mg), paritaprevir (12.5 mg) and ritonavir (50 mg) in one single tablet (two tablets once daily) and dasabuvir (250 mg) (one tablet twice daily) with ribavirin 800-1200 mg 12 weeks (Genotype 1b) or 24 weeks (genotype 1a) * Daily sofosbuvir (400 mg) and daily simeprevir (150 mg) +/- ribavirin 12-24 weeks * Daily sofosbuvir (400 mg) and daily daclatasvir (60 mg) +/- ribavirin 12-24 weeks
IF-DAAs	Simeprevir+Sofosbuvir	Interferon-free direct-acting antiviral combinations according to routine practice and European Guidelines (EASL recommendations 2015) * Fixed-dose combination of sofosbuvir (400 mg) and ledipasvir (90 mg) daily +/- ribavirin 12-24 weeks * Fixed-dose combination of ombitasvir (75 mg), paritaprevir (12.5 mg) and ritonavir (50 mg) in one single tablet (two tablets once daily) and dasabuvir (250 mg) (one tablet twice daily) with ribavirin 800-1200 mg 12 weeks (Genotype 1b) or 24 weeks (genotype 1a) * Daily sofosbuvir (400 mg) and daily simeprevir (150 mg) +/- ribavirin 12-24 weeks * Daily sofosbuvir (400 mg) and daily daclatasvir (60 mg) +/- ribavirin 12-24 weeks

Primary Outcome Measures

Name	Time	Method
sustained virological response (SVR)	12 weeks after treatment completion	undetectable HCV viral load 12 weeks after the end of antiviral treatment in each cohort of antiviral treatment

Secondary Outcome Measures

Name	Time	Method
Number of patients with gastroesophageal varices	gastroesophageal varices (GOV) before antiviral treatment and 12-24 weeks after treatment completion	Number of patients with GOV before and 12-24 weeks after treatment completion in patients with or without SVR