Hepatitis C Virus Infection in Patients With Hemoglobinopathies

Hepatitis C, Chronic Clinical Trial

Official title:

Treatment of Hepatitis C Virus Infection With Direct-acting Antiviral Drugs in Patients With Hemoglobinopathies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03149289
• Other study ID #: HCV-SITE
• Status: Completed
• Phase: N/A
• First received: April 14, 2017
• Last updated: May 9, 2017
• Start date: March 1, 2015
• Est. completion date: February 1, 2017

Study information

• Verified date: January 2017
• Source: Società Italiana Talassemie ed Emoglobinopatie
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication are efficacy to prevent liver complications. EASL and AASLD guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are very few This large, observational study evaluated the safety and efficacy of standard therapy with DAAs in a large Italian cohort of with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis.

Description:

Many patients with hemoglobinopathies have been infected with hepatitis C virus (HCV) through blood transfusion, mostly before screening of blood donors was introduced in 1992. The reported prevalence of anti-HCV-positive thalassemia patients varies between 4.4% in Turkey and 85.4% in Italy. HCV infection is associated with decompensated cirrhosis, hepatocellular carcinoma and other liver complications, especially if left untreated. Prevalence of cirrhosis in thalassemia patients up to 32% have been reported.

Thalassemia patients with cirrhosis have an increased risk of death. Progression of liver fibrosis is strongly related to the presence of chronic HCV infection and extent of iron overload. Thalassemia patients with elevated serum aminotransferase levels for >6 months should be tested for HCV infection and, in the event of HCV infection, HCV genotyping is recommended in order to plan antiviral therapy and the likelihood of response. Noninvasive transient elastography (FibroScan®) can be used to determine the presence of fibrosis in thalassemia patients with HCV infection.

Effective chelation therapy and treatment of HCV infection are needed in order to prevent liver complications and decrease morbidity and mortality. For many years, pegylated interferon (peg-IFN) plus ribavirin was the standard of care for the treatment of chronic HCV infection and decompensated cirrhosis. Studies of peg-IFN plus ribavirin have demonstrated sustained virological response (SVR) rates of 25−64% in patients with thalassemia and HCV infection. However, peg-IFN and ribavirin are both associated with anemia. Ribavirin-associated hemolysis leads to an increased requirement for blood transfusions, which in turn can lead to worsening of iron overload. Therefore, European Association for the Study of the Liver (EASL) 2015 guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. The aim of this study was to evaluate the safety and efficacy of DAA standard regimens in patients with hemoglobinopathies and chronic HCV liver disease treated in Italy.

Antiviral treatments were administered according to Italian Medicines Agency (AIFA) guidelines.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: February 1, 2017
• Est. primary completion date: March 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with hemoglobinopathies, chronic hepatitis due to HCV and the presence of fibrosis (defined as Fibroscan® stiffness =10 kPa) or a bioptic evaluation of cirrhosis (same ISHAK fibrosis score) determined within 6 months previously. Patients with extrahepatic manifestations of chronic hepatitis C virus infection (cryoglobulinemia with organ damage, B-lymphoproliferative disorders) were also included.

Exclusion Criteria:

• Patients with active cancer, including hepatocellular carcinoma, and pregnant or lactating females were excluded from the study

Related Conditions & MeSH terms

• Hemoglobinopathies
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Virus Diseases

Intervention

Drug:
• Antiviral drugs
sofosbuvir, ribavirin, daclatasvir, ledipasvir, simeprevir, paritaprevir, dasabuvir, ombitasvir

Locations

Country	Name	City	State
n/a

Sponsors (10)

Lead Sponsor	Collaborator
Società Italiana Talassemie ed Emoglobinopatie	Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello, Cardarelli Hospital, Ente Ospedaliero Ospedali Galliera, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Reggio Calabria, Second University of Naples, University of Cagliari, University of Palermo, University of Turin, Italy

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the number of participants with undetectable serum HCV RNA is being assessed at the end of treatment	The quantification of hepatitis virus particles in serum is assessed and expressed in IU/mL (IU, international units ) through quantitation of virus ribonucleic acid by real time polymerase chain reaction (PCR).	baseline and 12 weeks