Timing and Duration of Acute Hepatitis C Treatment

Hepatitis C Clinical Trial

Official title:

Phase IV Study of Treatment of Acute Hepatitis C With Pegylated Interferon

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00241618
• Other study ID #: 994058402
• Secondary ID: AI054887AI41563F
• Status: Completed
• Phase: Phase 4
• First received: October 18, 2005
• Last updated: September 7, 2006
• Start date: January 2002
• Est. completion date: January 2006

Study information

• Verified date: September 2006
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Institutional Review BoardUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Spontaneous resolution of acute hepatitis C infection cannot be predicted and the majority of cases persist and become chronic. This randomized trial assesses the efficacy and safety of peginterferon alfa-2b. The investigators hypothesize that therapy strategies could prevent the development of chronic hepatitis.

Description:

With nearly 4 million people in the United States, and an estimated 170-200 million people worldwide, the hepatitis C virus (HCV) represents a clear and significant public health issue. Unfortunately, for most people infected with HCV (70%-85%) spontaneous resolution is uncommon and 60% to 80% of patients with acute hepatitis C infection develop chronic hepatitis. This randomized trial focuses on defining the effect of treatment of acute HCV on prevention of chronic hepatitis in addition to optimization of the treatment regimen, onset and the length of peginterferon alpha therapy in acute hepatitis C infections. This randomized, multi-center prospective study assesses the efficacy of peginterferon in acute hepatitis. We will also compare differences in sustained viral response rates in patients with acute hepatitis C starting treatment at 8, 12, or 24 weeks. We will also compare the efficacy of 8, 12 or 24 weeks therapy with PEG-IFN-alpha. All eligible patients are enrolled and screened for an initial observation period starting from the time of their first positive HCV-RNA-PCR, during which bi-weekly serum ALT and HCV-RNA subjects were performed. Patients who did not resolve spontaneously (loss of HCV-RNA without treatment) by the end of the observation period were randomly assigned to receive PEG-IFN-alpha at the assigned onset and/or duration. Patients who do not consent to therapy at enrollment are included as a non-randomized comparison group. All subjects with SVR were followed for 48 weeks after the follow-up at 24 weeks when SVR was determined.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Age: 18-50 years, with or without symptoms

• Diagnosis of acute hepatitis C: elevated serum alanine aminotransferase (ALT) > 10 times the upper limit of normal (ULN)

• Seroconversion from negative to positive anti-HCV antibody status (third-generation enzyme-linked immunosorbent assay)

• Conversion from negative to positive polymerase chain reaction (PCR) for HCV-RNA, ruling out other causes of hepatitis by history and appropriate serologic and virologic studies.

Exclusion Criteria:

• Decompensated liver disease

• Coinfection with human immunodeficiency virus (HIV) or Schistosoma mansoni

• Marked anemia (hemoglobin level = 120 g/L in women and = 130 g/L in men)

• Neutropenia (< 1,500/mm3)

• Thrombocytopenia (< 90,000/mm3)

• A creatinine concentration > 1.5 times ULN

• Serum alpha-fetoprotein > 25 ng/ml

• An organ transplant

• Neoplastic disease

• Severe cardiac or pulmonary disease

• Unstable thyroid dysfunction

• A psychiatric disorder

• Seizure disorder

• Severe retinopathy

• A current pregnancy or were breast feeding or unwillingness to practice contraception

• Therapy with immunomodulatory agents within the last 6 months

• Alcohol or drug dependence within 1 year of study entry.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

Drug:
• Pegylated interferon alpha 2

• Ribavirin

Locations

Country	Name	City	State
Egypt	ASU	Cairo
Egypt	ASU Specialized Hospital	Cairo
Egypt	Shebin Liver Center	Cairo

Sponsors (8)

Lead Sponsor	Collaborator
Ain Shams University	Alexander von Humboldt Association, Beth Israel Deaconess Medical Center, Fulbright, International Society for Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), TEMPUS, University Hospital Freiburg

Country where clinical trial is conducted

Egypt, 

References & Publications (9)

Gerlach JT, Diepolder HM, Zachoval R, Gruener NH, Jung MC, Ulsenheimer A, Schraut WW, Schirren CA, Waechtler M, Backmund M, Pape GR. Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance. Gastroenterology. 2003 Jul;125(1):80-8. — View Citation

Jaeckel E, Cornberg M, Wedemeyer H, Santantonio T, Mayer J, Zankel M, Pastore G, Dietrich M, Trautwein C, Manns MP; German Acute Hepatitis C Therapy Group. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med. 2001 Nov 15;345(20):1452-7. — View Citation

Kamal SM, El Tawil AA, Nakano T, He Q, Rasenack J, Hakam SA, Saleh WA, Ismail A, Aziz AA, Madwar MA. Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response. Gut. 2005 Jun;54(6):858-66. — View Citation

Kamal SM, Ismail A, Graham CS, He Q, Rasenack JW, Peters T, Tawil AA, Fehr JJ, Khalifa Kel S, Madwar MM, Koziel MJ. Pegylated interferon alpha therapy in acute hepatitis C: relation to hepatitis C virus-specific T cell response kinetics. Hepatology. 2004 Jun;39(6):1721-31. — View Citation

Kamal SM, Rasenack JW, Bianchi L, Al Tawil A, El Sayed Khalifa K, Peter T, Mansour H, Ezzat W, Koziel M. Acute hepatitis C without and with schistosomiasis: correlation with hepatitis C-specific CD4(+) T-cell and cytokine response. Gastroenterology. 2001 Sep;121(3):646-56. — View Citation

Larghi A, Zuin M, Crosignani A, Ribero ML, Pipia C, Battezzati PM, Binelli G, Donato F, Zanetti AR, Podda M, Tagger A. Outcome of an outbreak of acute hepatitis C among healthy volunteers participating in pharmacokinetics studies. Hepatology. 2002 Oct;36(4 Pt 1):993-1000. — View Citation

Nomura H, Sou S, Tanimoto H, Nagahama T, Kimura Y, Hayashi J, Ishibashi H, Kashiwagi S. Short-term interferon-alfa therapy for acute hepatitis C: a randomized controlled trial. Hepatology. 2004 May;39(5):1213-9. — View Citation

Santantonio T, Sinisi E, Guastadisegni A, Casalino C, Mazzola M, Gentile A, Leandro G, Pastore G. Natural course of acute hepatitis C: a long-term prospective study. Dig Liver Dis. 2003 Feb;35(2):104-13. — View Citation

Wiegand J, Jäckel E, Cornberg M, Hinrichsen H, Dietrich M, Kroeger J, Fritsch WP, Kubitschke A, Aslan N, Tillmann HL, Manns MP, Wedemeyer H. Long-term follow-up after successful interferon therapy of acute hepatitis C. Hepatology. 2004 Jul;40(1):98-107. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained viral response rate in treatment group versus control
Secondary	End of treatment virologic response
Secondary	Early virologic response at week 4
Secondary	Quality of life