Clinical trial NCT00241618: Timing and Duration of Acute Hepatitis C Treatment
Official title: Phase IV Study of Treatment of Acute Hepatitis C With Pegylated Interferon
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis C
Keywords: Clinical trial
Randomized
Treatment
Prospective
Parallel Assignment
Efficacy Safety Study
Lead sponsor: Ain Shams University
Sponsor class: OTHER
Collaborators: name: University Hospital Freiburg
name: Beth Israel Deaconess Medical Center
name: Alexander von Humboldt Association
name: Fulbright
name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Tempus AI
name: International Society for Infectious Diseases
First posted: 2005-10-19
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Sustained viral response rate in treatment group versus control
Secondary outcomes:
measure: End of treatment virologic response
measure: Early virologic response at week 4
measure: Quality of life
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: ASU
city: Cairo
country: Egypt
facility: ASU Specialized Hospital
city: Cairo
country: Egypt
facility: Shebin Liver Center
Study officials:
affiliation: Ain Shams University
name: Alaa Ismail, M.D.
role: STUDY_CHAIR
affiliation: Ain Shams University
name: Sanaa M Kamal, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard Medical School (HMS and HSDM)
name: Nezam H Afdhal, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: ASU
name: Manal El Sayed, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1002/hep.20266.
citation: 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. doi: 10.1016/s0016-5085(03)00668-1.
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. doi: 10.1002/hep.20196.
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. doi: 10.1053/gast.2001.27024.
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. doi: 10.1016/s1590-8658(03)00007-0.
citation: Wiegand J, Jackel 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. doi: 10.1002/hep.20291.
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. doi: 10.1136/gut.2004.057182.
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. doi: 10.1056/NEJMoa011232.
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. doi: 10.1053/jhep.2002.36129.