Ribavirin Pre-treatment Followed by Combined Standard Therapy in Hepatitis C Virus (HCV) Recipients

NCT00993122 | Completed Phase 4 DMC

• 1 other identifier: Ribavirin Pre-treatment
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The results of antiviral therapy in patients with recurrent hepatitis C after liver transplantation are lower than standard. Ribavirin has immune-modulating effects and seems to be crucial to optimize viral treatment. The aim of this multicenter controlled study is to examine the effect of Ribavirin pre-treatment preceding the combination therapy with peginterferon plus ribavirin on the sustained virological response.

Conditions

Hepatitis C

Keywords

pre treatment; therapy compliance; SVR; sustained virological response; TH1 TH2 ratio

Outcome Measures

Primary Outcomes (1)

• HCV-RNA level, Transaminases level

  4°,12°,24°,36°48° week and six months after therapy conclusion

Secondary Outcomes (1)

• liver biopsy and Transient elastography at baseline and after six month since therapy conclusion

  0°, 72° week

Study Arms (2)

ribavirin pre-treatment

ACTIVE COMPARATOR

patient will receive ribavirin in monotherapy for 8 weeks before the combined 48 weeks antiviral therapy

Drug: ribavirin pre-treatment

combined stardard therapy

ACTIVE COMPARATOR

patients will receive the standard combined therapy with ribavirin and pegylated interferon for 48 weeks

Drug: ribavirin pre-treatment

Interventions

ribavirin pre-treatment DRUG

patients receive ribavirin (10,4 mg/kg/day) and pegylated interferon alfa-2b (1,5 mcg/kg/week).Pre-treatment arm will receive a 8-week monotherapy treatment with only ribavirin (same dosage) and the controlled arm will receive 48 week of standard combined therapy (ribavirin plus pegylated interferon)

Also known as: ribavirin pre treatment, ribavirin priming, Recurrence of hepatitis c, hepatitis c, transplanted patients, ribavirin, HCV

combined stardard therapy; ribavirin pre-treatment

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Liver transplantation from \> 6 months
• Positive HCV-RNA viremia
• Elevated transaminase levels (greater than 1,2 normal values) in at least two consecutive determinations during the last month
• Histology pattern showing hepatitis C recurrence

You may not qualify if:

• Multiple organ transplantation
• Histology showing evidence of hepatic allograft rejection \> 3/9 RAI score
• Concomitant active biliary disease
• Concomitant HBV infection
• Normal transaminases levels
• Less than 1500 neutrophiles in more than one blood test
• Less than 50000 platelets in more than one blood test
• Hemoglobin \< 9 g/ dL
• Creatinine clearance \< 35 ml/min
• Positive antibodies \> 1:80
• Auto-immune thyroid pathology
• Severe psychiatric disease
• Diagnosis of ischemic cardiopathy in the last 12 months
• Active alcohol abuse
• Low compliance to other medical treatments

Sponsors & Collaborators

• University of Roma La Sapienza: lead

Study Sites (1)

Sapienza University of Rome

Rome, Rome, 00100, Italy

Location

Related Publications (10)

• Gordon FD, Kwo P, Vargas HE. Treatment of hepatitis C in liver transplant recipients. Liver Transpl. 2009 Feb;15(2):126-35. doi: 10.1002/lt.21694.

  PMID: 19177439 BACKGROUND

• Furusyo N, Kubo N, Toyoda K, Takeoka H, Nabeshima S, Murata M, Nakamuta M, Hayashi J. Helper T cell cytokine response to ribavirin priming before combined treatment with interferon alpha and ribavirin for patients with chronic hepatitis C. Antiviral Res. 2005 Jul;67(1):46-54. doi: 10.1016/j.antiviral.2005.04.001.

  PMID: 15913800 BACKGROUND

• Feld JJ, Nanda S, Huang Y, Chen W, Cam M, Pusek SN, Schweigler LM, Theodore D, Zacks SL, Liang TJ, Fried MW. Hepatic gene expression during treatment with peginterferon and ribavirin: Identifying molecular pathways for treatment response. Hepatology. 2007 Nov;46(5):1548-63. doi: 10.1002/hep.21853.

  PMID: 17929300 BACKGROUND

• Ogawa K, Hige S, Nakanishi M, Yamamoto Y, Chuma M, Nagasaka A, Asaka M. Immunological and mutagenic actions of ribavirin monotherapy preceding combination therapy with interferon for patients with chronic hepatitis C. Antivir Ther. 2009;14(4):513-22.

  PMID: 19578236 BACKGROUND

• Tox U, Schulte S, Heindl B, Goeser T, Drebber U, Stelzer A, Steffen HM. Ribavirin priming in patients with chronic hepatitis C and normal ALT: a pilot study. Hepatogastroenterology. 2008 Sep-Oct;55(86-87):1666-70.

  PMID: 19102366 BACKGROUND

• Cuevas JM, Gonzalez-Candelas F, Moya A, Sanjuan R. Effect of ribavirin on the mutation rate and spectrum of hepatitis C virus in vivo. J Virol. 2009 Jun;83(11):5760-4. doi: 10.1128/JVI.00201-09. Epub 2009 Mar 25.

  PMID: 19321623 BACKGROUND

• Dixit NM, Perelson AS. The metabolism, pharmacokinetics and mechanisms of antiviral activity of ribavirin against hepatitis C virus. Cell Mol Life Sci. 2006 Apr;63(7-8):832-42. doi: 10.1007/s00018-005-5455-y.

  PMID: 16501888 BACKGROUND

• Berenguer M. Systematic review of the treatment of established recurrent hepatitis C with pegylated interferon in combination with ribavirin. J Hepatol. 2008 Aug;49(2):274-87. doi: 10.1016/j.jhep.2008.05.002. Epub 2008 May 22.

  PMID: 18571272 BACKGROUND

• Berenguer M, Prieto M, Rayon JM, Mora J, Pastor M, Ortiz V, Carrasco D, San Juan F, Burgueno MD, Mir J, Berenguer J. Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation. Hepatology. 2000 Oct;32(4 Pt 1):852-8. doi: 10.1053/jhep.2000.17924.

  PMID: 11003634 BACKGROUND

• Berenguer M, Lopez-Labrador FX, Wright TL. Hepatitis C and liver transplantation. J Hepatol. 2001 Nov;35(5):666-78. doi: 10.1016/s0168-8278(01)00179-9. No abstract available.

  PMID: 11690716 BACKGROUND

MeSH Terms

Conditions

Hepatitis C; Patient Compliance

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: October 8, 2009
• First Posted: October 12, 2009
• Study Start: October 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: February 1, 2012
• Last Updated: June 22, 2015

Record last verified: 2015-06

Locations

IT (1)