Clinical trial NCT00146016: Study on Chronic Hepatitis C Treatment With Interferon Alpha, Ribavirin and Amantadine in Naive Patients
Official title: Study on Chronic Hepatitis C Treatment With Interferon Alpha, Ribavirin and Amantadine in Naive Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis C
Keywords: Chronic Hepatitis C
Amantadine
Triple therapy
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
First posted: 2005-09-05
Enrollment: 390
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: \* Adding Amantadine to standard anti-viral treatment can improve sustained response rates in patients with chronic hepatitis C

Detailed description: The CIRA-study is a double blind, placebo controlled, randomised, multicentre study in previously untreated patients suffering from chronic hepatitis C comparing double therapy, consisting of (PEG-)interferon alpha 2b ((PEG)Intron-A®) and ribavirin (Rebetol®), with triple therapy, consisting of (PEG-)interferon alpha 2b, ribavirin and amantadine, for 52 weeks. Follow-up is completed at week 104. 150 Subjects per treatment group will be included. Patients will be stratified before randomisation according to genotype (1 versus non-1). Viral load will not be a discriminating factor.

The aim is to investigate the efficacy of the adjunct amantadine to the currently used combination therapy with interferon alpha and ribavirin.

Eligibility criteria: Inclusion Criteria:

* Anti-HCV positivity \>6 months
* ALT and/or AST elevation on at least once in the previous 6 months
* Positive HCV-RNA
* Liver biopsy within one year before the start of therapy in non- cirrhosis. In the case of known cirrhosis, liver biopsy is not necessary
* Intention to be treated and participate treatment
* Obtained written informed consent

Exclusion Criteria:

* Age \< 18 years
* Pregnancy or intention to get pregnant within the 12 months period of treatment and up to 6 months after discontinuation of therapy, no adequate contraception, lactation
* Men not practicing or willing to practice acceptable methods of contraception during the treatment period and up to 6 months after discontinuation of therapy
* Life expectancy \< 1 year
* Child Pugh B or C (Appendix III)
* Creatinine \> 150 μmol/L or \> 1.70 mg/dl
* Haemoglobulin \< 6.5 mmol/l or \< 10.5 g/dl
* White blood cell count \< 2,5 x 109/L, neutrophil \< 1,5 x 109/L
* Platelet count \< 70 x 109/L
* HIV positivity
* Chemotherapy, systematical antiviral treatment during the 6 months prior to study entry
* Other serious disease (e.g. malignancy, uncontrolled myocardial disease or severe arrhythmias)
* Active uncontrolled psychiatric disorders and suicidal leanings
* Patients with a history of uncontrolled seizure or other significant CNS dysfunction
* Any condition which in the opinion of the (co-)investigator might interfere with the evaluation of the study objectives

Primary outcomes:
measure: Response rate at end of treatment and end of follow-up (sustained response rate)
Secondary outcomes:
Other outcomes:
Locations:
city: Utrecht
country: Netherlands
facility: UMC Utrecht
Study officials:
affiliation: UMC Utrecht, dept. Gastroenterology
name: Karel v. Erpecum, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: UMC Utrecht, dept gastroenterology
name: Melvin Samsom, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berg T, Kronenberger B, Hinrichsen H, Gerlach T, Buggisch P, Herrmann E, Spengler U, Goeser T, Nasser S, Wursthorn K, Pape GR, Hopf U, Zeuzem S. Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C: a placebo-controlled trial. Hepatology. 2003 Jun;37(6):1359-67. doi: 10.1053/jhep.2003.50219.
citation: Brillanti S, Levantesi F, Masi L, Foli M, Bolondi L. Triple antiviral therapy as a new option for patients with interferon nonresponsive chronic hepatitis C. Hepatology. 2000 Sep;32(3):630-4. doi: 10.1053/jhep.2000.16235.
citation: Younossi ZM, McCullough AC, Barnes DS, Post A, Ong JP, O'Shea R, Martin LM, Bringman D, Farmer D, Levinthal G, Mullen KD, Carey WD, Tavill AS, Ferguson R, Gramlich T. Pegylated interferon alpha-2b, ribavirin and amantadine for chronic hepatitis C. Dig Dis Sci. 2005 May;50(5):970-5. doi: 10.1007/s10620-005-2673-y.
citation: Van Vlerken LG, Van Soest H, Janssen MP, Boland GJ, Drenth JP, Burger DM, Siersema PD, Van Erpecum KJ. Suboptimal endogenous erythropoietin response in chronic hepatitis C patients during ribavirin and PEG interferon treatment. Eur J Gastroenterol Hepatol. 2010 Nov;22(11):1308-15. doi: 10.1097/MEG.0b013e32833e784d.