Skip to main content
OpenTrials
Completed

NCT Number: NCT00759109

Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085)

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Carcinoma, Hepatocellular Adenocarcinoma Carcinoma Digestive System Diseases Digestive System Neoplasms Liver Diseases Liver Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Peginterferon alfa-2b

Biological

Peginterferon alfa-2b, 50 μg, weekly, SC, for a period of 3 years.

Other names: PegIntron, Pegylated Alfa-2b, SCH 054031

Observation (no treatment)

Other

No treatment was given to participants enrolled in the control arm (Arm B).

Primary outcomes

  1. Number of Participants With the Development of Hepatocellular Carcinoma (HCC)

    Time frame: During 3 years of treatment and 2 years of follow-up

    Participants were tested for focal lesions by liver ultrasound and for AFP levels every 6 months the during study (treatment and follow-up).

    The development of hepatocellular carcinoma was determined by:

    • the appearance of a focal lesion detected by liver ultrasound with metastases confirmed by fine needle biopsy, or
    • the appearance of a focal lesion detected by ultrasound + alphafetoprotein (AFP) levels in blood >400 ng/mL.

Secondary outcomes

  1. Number of Participants With Development of Hepatic Decompensation

    Time frame: Baseline, During 3 years of treatment and 2 years of follow-up

    The development of hepatic decompensation, defined as worsening of the hepatic function as measured by Child Pugh Score. The Child Pugh score was calculated based on biochemical changes (changes in serum albumin, serum bilirubin, prothrombin time) and clinical impairment (ascites, encephalopathies) or both. Each of the 5 parameters was scored from 1-3, and the Child Pugh Score represented the total score. The maximum score was 15, and a score of 10-15 represents the worst outcome and a life expectancy of 1-3 years.

  2. Survival Time of Participants

    Time frame: During 3 years of treatment and 2 years of follow-up

    Survival time was defined as time from screening visit to the death of the participant and was studied with Kaplan-Meier and Log-rank tests. If a participant did not die, he or she was censored with the last available date.

  3. Number of Patients With a Virological Response Rate

    Time frame: Baseline and every year during 3 years of treatment

    Virological Response rate was measured by the disappearance of Hepatitis C Virus from serum. Serum samples from participants were analyzed for the

    presence of HCV-RNA using a qualitative polymerase chain reaction (PCR).

  4. Change in the Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI)

    Time frame: Baseline and at 18 months of treatment

    PCNA-LI was measured at baseline and at 18 months of treatment, and the change in PCNA-LI was calculated.

    To measure PCNA-LI, liver tissue samples obtained from biopsies were fixed and immunostained to detect PCNA. PCNA-LI is the percentage of immunohistochemically stained (PCNA positive) cells in 1,000 HCC cells counted. A higher PCNA-LI indicates a worse outcome.

Other outcomes

  1. Proliferating Cell Nuclear Antigen Labeling Index (PCNA-LI) at Baseline

    Time frame: Baseline

    Liver tissues obtained from biopsies were fixed and immunostained to detect PCNA. PCNA-LI is the percentage of immunohistochemically stained (PCNA positive) cells in 1,000 HCC cells counted. A higher PCNA-LI indicates a worse outcome.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Important dates

Study start
2002
Primary completion
2009
Study completion
2009
First posted
Sep 25, 2008
Registry last updated
Apr 7, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.