Back to resultsRibavirin Dose Optimization for the Treatment of Hepatitis C
Primary Purpose
Chronic Hepatitis C
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Peg-interferon alpha-2a, Ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Ribavirin, Pegasys, Hepatitis
Eligibility Criteria
Inclusion Criteria:
- Age > 18 years
- Chronic hepatitis C and failure of prior treatment with peginterferon plus ribavirin (non-response: HCV-RNA decreased less than 2 logs after 3 months of treatment; relapse: HCV-RNA that becomes positive again after treatment is stopped
- Compensated hepatic disease (Child-Pugh ≤ 6)
- Provision by patient of his or her written consent
Exclusion Criteria:
- Females who are pregnant or lactating will be excluded
- Renal failure (estimated glomerular filtration rate < 50 ml/min)
- A contraindication to treatment with peginterferon plus ribavirin (uncontrolled psychiatric illness, pregnancy/nursing/non-use of effective contraceptive method, uncontrolled epilepsy for at least 6 months, heart failure, unstable angina, hemoglobin < 120 g/L, neutrophils < 1,000/mm3, platelets < 50 x 109/L, or any other condition that, in the investigator's opinion, contraindicates use of the treatment)
Sites / Locations
- Centre hospitalier de l'Université de Montréal
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Peg-interferon alpha-2a, Ribavirin
Arm Description
Adult patients with chronic hepatitis C and failure of prior treatment with peginterferon plus ribavirin(non-response or relapse). This is a pilot study with no control group.
Outcomes
Primary Outcome Measures
Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) analysis assay
Qualitative
Secondary Outcome Measures
Viral Kinetics
Plasma Ribavirin (RBV) Assays; Immune Response
Neutrophils
If neutrophils are < 500/mm, neupogen may be added
Hemoglobin
If hemoglobin is < 100g/L, erythropoietin and/or transfusions may be prescribed
Full Information
NCT ID
NCT01289496
First Posted
January 25, 2011
Last Updated
February 24, 2014
Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborators
Hoffmann-La Roche, Centre de Recherche du Centre Hospitalier de l'Université de Montréal
1. Study Identification
Unique Protocol Identification Number
NCT01289496
Brief Title
Ribavirin Dose Optimization for the Treatment of Hepatitis C
Official Title
Ribavirin Dose Optimization for the Treatment of Hepatitis C: A Pilot Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre hospitalier de l'Université de Montréal (CHUM)
Collaborators
Hoffmann-La Roche, Centre de Recherche du Centre Hospitalier de l'Université de Montréal
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Patients for whom treatment with peginterferon plus ribavirin was unsuccessful represent a category of patients for whom there is currently no worthwhile therapeutic alternative.
Several studies have shown that there is a relation between plasma ribavirin concentrations and treatment response. Adequate ribavirin plasma concentrations, especially during the first 12 weeks of treatment, should be associated with a better chance of response to the treatment.
The strategy for this study will be to use a loading dose of ribavirin before beginning the treatment with peg-interferon, thereby allowing for optimal ribavirin concentrations to be reached, and possibly improving the effectiveness of the treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C
Keywords
Ribavirin, Pegasys, Hepatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Peg-interferon alpha-2a, Ribavirin
Arm Type
Experimental
Arm Description
Adult patients with chronic hepatitis C and failure of prior treatment with peginterferon plus ribavirin(non-response or relapse).
This is a pilot study with no control group.
Intervention Type
Drug
Intervention Name(s)
Peg-interferon alpha-2a, Ribavirin
Other Intervention Name(s)
Peg-interféron alpha-2a (PEGASYS), Ribavirin (COPEGUS)
Intervention Description
4 weeks RBV priming;
24 or 48 weeks of Pegasys+Ribavirin (RBV) Treatment (depending on genotype);
24 weeks Follow-Up
Patients will receive PEGASYS® 180 µg in 0.5 mL (prefilled syringes) administered sc once weekly. Specific guidelines for adjusting the dose of PEGASYS® are provided in the product monograph.All PEGASYS® administrations will be via the sc route using sterile technique.
Ribavirin 200 mg tablets
Primary Outcome Measure Information:
Title
Hepatitis C Virus-Ribonucleic Acid (HCV-RNA) analysis assay
Description
Qualitative
Time Frame
up to 24 weeks post treatment
Secondary Outcome Measure Information:
Title
Viral Kinetics
Description
Plasma Ribavirin (RBV) Assays; Immune Response
Time Frame
up to 24 weeks post treatment
Title
Neutrophils
Description
If neutrophils are < 500/mm, neupogen may be added
Time Frame
up to 24-48 weeks of treatment
Title
Hemoglobin
Description
If hemoglobin is < 100g/L, erythropoietin and/or transfusions may be prescribed
Time Frame
up to 24-48 weeks of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age > 18 years
Chronic hepatitis C and failure of prior treatment with peginterferon plus ribavirin (non-response: HCV-RNA decreased less than 2 logs after 3 months of treatment; relapse: HCV-RNA that becomes positive again after treatment is stopped
Compensated hepatic disease (Child-Pugh ≤ 6)
Provision by patient of his or her written consent
Exclusion Criteria:
Females who are pregnant or lactating will be excluded
Renal failure (estimated glomerular filtration rate < 50 ml/min)
A contraindication to treatment with peginterferon plus ribavirin (uncontrolled psychiatric illness, pregnancy/nursing/non-use of effective contraceptive method, uncontrolled epilepsy for at least 6 months, heart failure, unstable angina, hemoglobin < 120 g/L, neutrophils < 1,000/mm3, platelets < 50 x 109/L, or any other condition that, in the investigator's opinion, contraindicates use of the treatment)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Pierre Villeneuve, M.D., Ph.D.
Organizational Affiliation
Centre hospitalier de l'Université de Montréal (CHUM)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre hospitalier de l'Université de Montréal
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X1P1
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
12680884
Citation
Tsubota A, Hirose Y, Izumi N, Kumada H. Pharmacokinetics of ribavirin in combined interferon-alpha 2b and ribavirin therapy for chronic hepatitis C virus infection. Br J Clin Pharmacol. 2003 Apr;55(4):360-7. doi: 10.1046/j.1365-2125.2003.01780.x.
Results Reference
background
PubMed Identifier
17118126
Citation
Wade JR, Snoeck E, Duff F, Lamb M, Jorga K. Pharmacokinetics of ribavirin in patients with hepatitis C virus. Br J Clin Pharmacol. 2006 Dec;62(6):710-4. doi: 10.1111/j.1365-2125.2006.02704.x.
Results Reference
background
PubMed Identifier
18672540
Citation
Maynard M, Pradat P, Gagnieu MC, Souvignet C, Trepo C. Prediction of sustained virological response by ribavirin plasma concentration at week 4 of therapy in hepatitis C virus genotype 1 patients. Antivir Ther. 2008;13(4):607-11.
Results Reference
background
PubMed Identifier
17253142
Citation
Cheruvattath R, Rosati MJ, Gautam M, Vargas HE, Rakela J, Balan V. Pegylated interferon and ribavirin failures: is retreatment an option? Dig Dis Sci. 2007 Mar;52(3):732-6. doi: 10.1007/s10620-006-9457-x.
Results Reference
background
PubMed Identifier
10349689
Citation
Glue P. The clinical pharmacology of ribavirin. Semin Liver Dis. 1999;19 Suppl 1:17-24.
Results Reference
background
PubMed Identifier
15681898
Citation
Uchida M, Hamada A, Yamasaki M, Fujiyama S, Sasaki Y, Saito H. Assessment of adverse reactions and pharmacokinetics of ribavirin in combination with interferon alpha-2b in patients with chronic hepatitis C. Drug Metab Pharmacokinet. 2004 Dec;19(6):438-43. doi: 10.2133/dmpk.19.438.
Results Reference
background
PubMed Identifier
15812187
Citation
Arase Y, Ikeda K, Tsubota A, Suzuki F, Suzuki Y, Saitoh S, Kobayashi M, Akuta N, Someya T, Hosaka T, Sezaki H, Kobayashi M, Kumada H. Significance of serum ribavirin concentration in combination therapy of interferon and ribavirin for chronic hepatitis C. Intervirology. 2005;48(2-3):138-44. doi: 10.1159/000081741.
Results Reference
background
PubMed Identifier
18667516
Citation
Badr G, Bedard N, Abdel-Hakeem MS, Trautmann L, Willems B, Villeneuve JP, Haddad EK, Sekaly RP, Bruneau J, Shoukry NH. Early interferon therapy for hepatitis C virus infection rescues polyfunctional, long-lived CD8+ memory T cells. J Virol. 2008 Oct;82(20):10017-31. doi: 10.1128/JVI.01083-08. Epub 2008 Jul 30.
Results Reference
background
PubMed Identifier
20399525
Citation
Hofer H, Donnerer J, Sator K, Staufer K, Scherzer TM, Dejaco C, Sator M, Kessler H, Ferenci P. Seminal fluid ribavirin level and functional semen parameters in patients with chronic hepatitis C on antiviral combination therapy. J Hepatol. 2010 Jun;52(6):812-6. doi: 10.1016/j.jhep.2009.12.039. Epub 2010 Mar 23.
Results Reference
background
PubMed Identifier
11034261
Citation
Jen JF, Glue P, Gupta S, Zambas D, Hajian G. Population pharmacokinetic and pharmacodynamic analysis of ribavirin in patients with chronic hepatitis C. Ther Drug Monit. 2000 Oct;22(5):555-65. doi: 10.1097/00007691-200010000-00010.
Results Reference
background
PubMed Identifier
12386637
Citation
Jen J, Laughlin M, Chung C, Heft S, Affrime MB, Gupta SK, Glue P, Hajian G. Ribavirin dosing in chronic hepatitis C: application of population pharmacokinetic-pharmacodynamic models. Clin Pharmacol Ther. 2002 Oct;72(4):349-61. doi: 10.1067/mcp.2002.127112.
Results Reference
background
PubMed Identifier
19380853
Citation
Jensen DM, Marcellin P, Freilich B, Andreone P, Di Bisceglie A, Brandao-Mello CE, Reddy KR, Craxi A, Martin AO, Teuber G, Messinger D, Thommes JA, Tietz A. Re-treatment of patients with chronic hepatitis C who do not respond to peginterferon-alpha2b: a randomized trial. Ann Intern Med. 2009 Apr 21;150(8):528-40. doi: 10.7326/0003-4819-150-8-200904210-00007.
Results Reference
background
PubMed Identifier
6175589
Citation
Kauppila A, Cantell K, Janne O, Kokko E, Vihko R. Serum sex steroid and peptide hormone concentrations, and endometrial estrogen and progestin receptor levels during administration of human leukocyte interferon. Int J Cancer. 1982 Mar 15;29(3):291-4. doi: 10.1002/ijc.2910290311.
Results Reference
background
PubMed Identifier
18435468
Citation
Loustaud-Ratti V, Alain S, Rousseau A, Hubert IF, Sauvage FL, Marquet P, Denis F, Lunel F, Cales P, Lefebvre A, Fauchais AL, Liozon E, Vidal E. Ribavirin exposure after the first dose is predictive of sustained virological response in chronic hepatitis C. Hepatology. 2008 May;47(5):1453-61. doi: 10.1002/hep.22217.
Results Reference
background
PubMed Identifier
14749543
Citation
Maeda Y, Kiribayashi Y, Moriya T, Maruhashi A, Omoda K, Funakoshi S, Murakami T, Takano M. Dosage adjustment of ribavirin based on renal function in Japanese patients with chronic hepatitis C. Ther Drug Monit. 2004 Feb;26(1):9-15. doi: 10.1097/00007691-200402000-00004.
Results Reference
background
Learn more about this trial
Ribavirin Dose Optimization for the Treatment of Hepatitis C
We'll reach out to this number within 24 hrs