Retreatment of chronic hepatitis C patients with pegylated interferon (IFN), ribavirin and amantadine; a pilot study to establish if initial drop in viral load is predictive for sustained virological response
| ISRCTN | ISRCTN81536220 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN81536220 |
| Secondary identifying numbers | N/A |
- Submission date
- 14/02/2006
- Registration date
- 14/02/2006
- Last edited
- 25/02/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Dr Huub Gelderblom
Scientific
Scientific
Academic Medical Center (AMC)
Department of Gastroenterology
AMC Liver Center
C2-331
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
| Phone | +31 (0)20 5668748 |
|---|---|
| h.c.gelderblom@amc.nl |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Not Specified |
| Scientific title | Retreatment of chronic hepatitis C patients with pegylated interferon (IFN), ribavirin and amantadine; a pilot study to establish if initial drop in viral load is predictive for sustained virological response |
| Study acronym | VKF2 |
| Study objectives | 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(s) | Not provided at time of registration |
| Health condition(s) or problem(s) studied | 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/01/2002 |
| Completion date | 01/01/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 61 |
| Total final enrolment | 100 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 01/01/2002 |
| Date of final enrolment | 01/01/2007 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
Academic Medical Center (AMC)
Amsterdam
1100 DD
Netherlands
1100 DD
Netherlands
Sponsor information
Academic Medical Center (AMC), Department of Gastroenterology, AMC Liver Center (The Netherlands)
Not defined
Not defined
P.O. Box 22660
Amsterdam
1100 DD
Netherlands
"ROR" |
https://ror.org/03t4gr691 |
|---|
Funders
Funder type
Industry
Schering-Plough
Private sector organisation / For-profit companies (industry)
Private sector organisation / For-profit companies (industry)
- Location
- United States of America
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/04/2008 | 25/02/2021 | Yes | No |
Editorial Notes
The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
