Clinical trial NCT00759109: Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085)
Official title: Long-term Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation: a Multicenter Study of Hepatocellular Carcinoma Prevention in Patients Non-responders to Combined Therapy With Alpha Interferon + Ribavirin or Peginterferon Alpha + Ribavirin or to Interferon Monotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-09-25
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study aims to compare the role of peginterferon α-2b (50 μg/week) vs. control (no treatment) in the prevention of hepatocellular carcinoma, in adult patients with cirrhosis and initial signs of portal hypertension who did not respond to previous combined therapy with interferon alfa + ribavirin or peginterferon alfa + ribavirin or to interferon alfa monotherapy and with a high proliferation rate before entering the study. The duration of treatment will be 3 years, and the follow-up period will be 2 years.


Eligibility criteria: Inclusion Criteria:

* Cirrhotic participants, both sexes, Child Pugh A, B, HCV-RNA positive, age \< 70 years
* Participants non-responders to IFN + Ribavirin or PegIFN + Ribavirin or IFN monotherapy
* Pre-therapy liver biopsy (\< 36 months) with PCNA-LI \> 2.0
* Fibrosis score 5-6 (Ishak)
* Initial portal hypertension, such as gastroesophageal varices or one of the following US sign:

  * Collateral circles
  * Spleen longitudinal diameter \> 12 cm
  * Portal vein diameter at hilus \> 12 mm
  * Portal flow \> 12 cm/sec
  * Participants must have the following minimum hematologic and biochemical criteria:
  * Hemoglobin \>= 11 g/dL
  * Granulocyte count \> 1,000/mm\^3
  * Platelets \> 70,000/mm\^3
  * Prothrombin activity \> 50%
  * Total bilirubin \<3 mg/dL
  * Albumin \>= 3.5 g/dL
  * Serum creatinine within normal limits
* Uric Acid within normal limits
* Thyroid Stimulating Hormone (TSH), within normal limits
* Antinuclear antibodies (ANA) \< 1:160
* Written informed consent
* Women of childbearing potential must have a negative pregnancy test
* Acceptance of patients of both sexes of proper contraceptive measures for the study period

Exclusion Criteria:

* Pregnant or breast-feeding women
* Co-infection with HIV and/or HBV
* Autoimmune hepatitis or history of autoimmune disease
* Alcoholic liver disease
* Metabolic disease
* HCC
* Participants with liver and kidney transplants
* Evidence of decompensated liver disease such as history or presence of ascites, bleeding varices, spontaneous encephalopathy
* Chronic renal failure or creatinine clearance \< 50 mL/min
* Pre-existing thyroid disease unless it can be controlled with conventional treatment
* History or presence of psychiatric condition, especially depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt
* Epilepsy and/or compromised central nervous system (CNS) function
* Significant cardiovascular dysfunction within the previous 6 months before the study starts (eg, angina, congestive heart failure, recent myocardial infarction, moderate or severe hypertension, significant arrhythmia)
* Hemoglobinopathies
* Poorly controlled diabetes mellitus
* Chronic pulmonary disease (eg, chronic obstructive pulmonary disease)
* Clinical gout
* Hypersensitivity to interferons or any component of the drug

Primary outcomes:
measure: Number of Participants With the Development of Hepatocellular Carcinoma (HCC)
timeFrame: During 3 years of treatment and 2 years of follow-up
Secondary outcomes:
measure: Number of Participants With Development of Hepatic Decompensation
timeFrame: Baseline, During 3 years of treatment and 2 years of follow-up
measure: Survival Time of Participants
timeFrame: During 3 years of treatment and 2 years of follow-up
measure: Number of Patients With a Virological Response Rate
timeFrame: Baseline and every year during 3 years of treatment
measure: Change in the Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI)
timeFrame: Baseline and at 18 months of treatment
Other outcomes:
measure: Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI) at Baseline
timeFrame: Baseline
Locations:
Study officials:
References: