Pegylated Alfa-2b Interferon Therapy of Patients With Hepatitis C-related Cirrhosis and High Liver Cell Proliferation (P02733/MK-4031-085)
|Carcinoma, Hepatocellular||Biological: Peginterferon alfa-2b Other: Observation (no treatment)||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
|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|
- 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.
- 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.
- 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.
- 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).
- 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.
- 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.
|Study Start Date:||March 2002|
|Study Completion Date:||November 2009|
|Primary Completion Date:||November 2009 (Final data collection date for primary outcome measure)|
Experimental: Arm A - PegIntron
Participants randomized to Arm A received peginterferon α-2b (PegIntron), 50 μg, weekly, subcutaneously (SC), for a period of 3 years.
Biological: Peginterferon alfa-2b
Peginterferon alfa-2b, 50 μg, weekly, SC, for a period of 3 years.
Arm B - Control
Participants randomized to Arm B were under observation and received no treatment.
Other: Observation (no treatment)
No treatment was given to participants enrolled in the control arm (Arm B).