Contact information
Type
Scientific
Primary contact
Dr Huub Gelderblom
ORCID ID
Contact details
Academic Medical Center (AMC)
Department of Gastroenterology
AMC Liver Center
C2-331
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
+31 (0)20 5668748
h.c.gelderblom@amc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
VKF2
Study hypothesis
In this study are patients with chronic hepatitis C with a previous virological relapse or a virological non response to IFN or IFN/Ribavirin combination therapy, with a high induction dose of pegylated Interferon combined with Ribavirin and Amantadine. Subsequently a lower dose pegylated Interferon combined with Ribavirin and Amantadine is given to the patients. The aim of the study is to determine if a drop in viral load in the first 4 weeks of treatment is predictive for virological sustained response.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Not Specified
Patient information sheet
Condition
Hepatitis C
Intervention
This study will be an open pilot study. Data will be analysed on an intention to treat basis.
Eighty patients will be included.
All patients:
2 weeks Intron A (3 x 6 MU daily), Ribavirin (1000-1200 mg daily) and Amantadine (200 mg daily), 2 weeks Intron A (3 x 3 MU daily), Ribavirin (1000-1200 mg daily) and Amantadine (200 mg daily), 2 weeks Intron A (2 x 3 MU daily), Ribavirin (1000-1200 mg daily) and Amantadine (200 mg daily).
After 6 weeks of induction therapy, 3 groups of patients will be divided according to their viral load decline.
Viral load decline calculated by the equation:
Viral load decline = Viral load at day 0 – Viral load at week 4
Viral load expressed in log.
Group 1, non responders: =/< 0.5 log decline in viral load
Group 2, slow responders: >0.5 - <3 log decline in viral load
Group 3, rapid responders: >/= 3 log decline in viral load
Non-responders (group 1) and slow responders (group 2):
42 weeks: Pegylated Interferon 1.5 microgram/kg/week, Ribavirin 1000-1200 mg a day, Amantadine 200 mg a day.
Treatment will be stopped at week 28 when patients are still HCV-RNA positive at week 24 of treatment.
Rapid responders (group 3):
Patients will be randomised to receive either:
Group 3A: 22 weeks treatment: Pegylated Interferon 1.5 microgram/kg/week, Ribavirin 1000-1200 mg a day, Amantadine 200 mg a day
OR
Group 3B: 42 weeks treatment: Pegylated Interferon 1.5 microgram/kg/week, Ribavirin 1000-1200 mg a day, Amantadine 200 mg a day
Treatment will be stopped at week 28 in all patients who are HCV-RNA positive at week 24 of treatment.
Intervention type
Drug
Phase
Not Specified
Drug names
pegylated interferon, ribavirin and amantadine.
Primary outcome measure
To determine if initial drop in viral load is predictive for virological sustained response.
Secondary outcome measures
To determine if other co-factors i.e. viral load or HCV genotype are predictive for sustained virological response.
Overall trial start date
01/01/2002
Overall trial end date
01/01/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients with a chronic hepatitis C virus (HCV) infection, with virological relapse, or with virological non response to previous antiviral therapy diagnosed by
a. Anti-HCV positive
b. Serum HCV-RNA positive by polymerase chain reaction (PCR)
2. Patients who have not used antiviral or immune modulating therapy, including interferon, in the previous 6 months
3. Male and female patients >18 and <65 years of age
4. Patients who have given written informed consent after a detailed explanation of the study by the investigator
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
61
Participant exclusion criteria
1. Patients who are pregnant and patients (male or female) who are not willing to practise adequate contraception during the treatment period and up to 6 months after ending the treatment period
2. Patients who are HBsAg or HIV antibody positive or are unwilling to have these tests done
3. Patients with decompensated cirrhosis (e.g. albumin <32 g/l, PTT prolonged >4 s, bilirubin > upper limit of normal, AT III <60%, ascites, gastrointestinal [GI] bleeding, encephalopathy)
4. Patients with a history of intravenous (iv) drug use within 6 months prior to entry
5. Patients with any clinically significant systemic disease other than liver disease (e.g. malignant disease, congestive heart failure, uncontrolled diabetes mellitus, renal failure [serum creatinine >181 micromol/ml], or autoimmmune disease)
6. Patients with a history of auto-immune hepatitis
7. Patients using immune modulating treatment during the 6 months prior to study entry
8. Patients with a history of hypersensitivity to any component of the study drugs
9. Patients with pre-existing bone marrow depression such as hematocrit <32%, white blood cell count <3.0 x 10^9/l, granulocytes <10%, platelets <100 x 10^9/l, neutrophil count <1.5 x 10^9 or Hemoglobin <8.1 mmol/l for males and <7.5 mmol/l for females
10. Patients with severe depression or other psychiatric illness
11. Patients with a history of epilepsy, or other clinically significant central nervous system (CNS) dysfunction
12. Patients with any condition, that in the opinion of the investigator, might interfere with the outcome of the study
Recruitment start date
01/01/2002
Recruitment end date
01/01/2007
Locations
Countries of recruitment
Netherlands
Trial participating centre
Academic Medical Center (AMC)
Amsterdam
1100 DD
Netherlands
Funders
Funder type
Industry
Funder name
Schering-Plough
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list