Interferon/Ribavirin-Free Sofosbuvir Based Treatment (AURIC) (AURIC)

Interferon/Ribavirin-Free Sofosbuvir Based Treatment Regimens In Patients With Advanced Liver Disease - Results Of A Real-Life Austrian Ribavirin-/Interferon Free Cohort (AURIC)

Since the availability of interferon free direct acting antivirals (DAA) the centers authorized to prescribed these drugs in Austria submitted their data to a central data base (AURIC) using treatment regimes without interferon and ribavirin in patients with advanced liver disease (F3/4)

Study Overview

• Status: Completed
• Conditions: Cirrhosis; Chronic Hepatitis C

Detailed Description

From end of 2013 303 HCV-monoinfected patients with advanced liver disease (F3/4) were treated with interferon (IFN)-free and RBV-free SOF-based regimens. During this period only 7 patients received additional RBV. These patients were not included in this analysis. Only patients who completed 12 weeks of treatment-free follow up until July 2015 were included in this analysis. In Austria, prescription of DAAs is restricted to specialized treatment centers. Data are obtained by 6 participating centers and submitted to the central database forming for of the Austrian Ribavirin- and Interferon-free cohort (AURIC). Incoming data are reviewed by the staff of the hepatitis study group of the Dept. of Medicine III, Medical university of Vienna.The treatment regimens consisted of SOF/DCV, SOF/SMV, and SOF/LDV. The duration of treatment was based on a response guided approach at the discretion of the treating physician (12 or 24 weeks).

Sixty six patients who had started therapy before August 2014 received SMV or DCV as part of a named patient program, SOF was prescribed. For the remaining patients all drugs were prescribed and paid for by the Austrian social insurance.

This study will investigate various aspects of treatment response to regimens containing direct-acting antiviral agents for the treatment of chronic hepatitis C:

Sustained virologic response (SVR) defined as undetectable HCV-RNA after 12 weeks of treatment free follow up

Virological breakthrough/relapse defined as reappearance of HCV on treatment/during follow up

Impact of viral kinetics on prediction of treatment efficacy: Viral load measured repeatedly (at baseline, on days 2,7,14,21,28,and than every 4 weeks until end of treatment) allows to study the rapidity of viral clearance. This parameter was used to assess whether length of treatment can be modified. Plasma HCV RNA levels were quantified by One Signal Amplification (Versant HCV RNA 3.0),

Adverse Event Recording (using standard GCP criteria)

Longterm outcome after SVR based on examining patients with SVR in six monh intervals. Examination will include liver sonography, elastography, routine blood chemistry including alpha1-fetoprotein

• Study Type: Observational
• Enrollment (Actual): 558

Contacts and Locations

Study Locations

• Austria
  • Wien, Austria, A1090
    • Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients with fibrosis grade F3 or F4, age >18 years, with indication for antiviral treatment

Description

Inclusion Criteria:

• All adult patients (age 18 or older) being treated with antiviral HCV treatment regimens

Exclusion Criteria:

• other disease with poor prognosis (ie. metastatic cancer, heart failure)
• participation in a clinical trial

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
SOF/SMV; SOF/SMV 400mg/150mg QD 12-24 weeks
SOF/DCV; SOF/DCV 400mg/60mg QD 12-24 weeks
SOF/LDV; SOF/LDV 400mg/90mg QD 12-24 weeks
treatment duration; 12 - 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with sustained virologic response (SVR)	SVR is defined by the undetectability of HCV-RNA after 12 weeks of treatment free follow up	12 weeks treatment free follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
On treatment predictability of SVR	Virus testing at baseline, day 2,7,14,21,28, than every 4 weeks until SVR. Rapidity of viral clearance may be a useful parameter to determine the duration of treatment	12/24 weeks of treatment + 12 weeks of follow up
Number of patients with liver events (Mortality, Hepatic decompensation, Variceal Bleeding,Hepatocellular Carcinoma, Need for Liver Transplantation) on longterm clinical outcome	regular clinical visits including laboratory test, fibroscan and sonography will be performed every six months after achieving SVR	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	adverse events will be recorded and graded	treatment (12 to 24 weeks) +12weeks treatment free follow up

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Harald Hofer, MD,Prof, Medical University of Vienna

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 8, 2015
• First Posted (Estimate): December 11, 2015

Study Record Updates

• Last Update Posted (Actual): September 6, 2017
• Last Update Submitted That Met QC Criteria: September 2, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Hepatitis C; sofosbuvir; daclatasvir; ledipasvir; simeprevir
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: I3MHCV