Hepatitis C VirusPhase 4NCT01195181
Different PEG-interferon and Ribavirin Schedules for Chronic Hepatitis C in the Real Clinical Practice.
A Phase 4 study testing peginterferon plus ribavirin in people with Hepatitis C Virus and Chronic Liver Disease, run by Azienda Ospedaliera di Padova at 1 site in Italy.
Trial summary
Hepatitis C virus (HCV) infection provokes thousands of deaths every year all over the world, being the major cause of progressive liver disease, primary hepatic cancer and liver transplantation. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C Virus, Chronic Liver Disease, Viral Hepatitis
- What is being tested?
- peginterferon plus ribavirin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 506 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2005to Aug 2010
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Naive adult subject
- active HCV infection (HCV-RNA positive)
- histological/biochemical signs of chronic hepatitis or compensated cirrhosis
- willingness of treatment
Who cannot join
- autoimmune disorders
- severe depression or psychiatric disease
- previous decompensation of cirrhosis
- gastroesophageal bleeding
- hepatocellular carcinoma
- major disease with a life expectancy of less than 5 years
- pregnancy or nursing
Trial locations and contacts
1 site in 1 country.
Italy1 site
Department of Clinical and Experimental Medicine, Out-patients Hepatologic Unit, Azienda Ospedaliera di Padova.
Padua, 35100
About this study
Official title: Improvement of the Surveillance and Control of Liver Disease and Complication Due to Chronic Hepatitis C: Project A) Antiviral Drugs Use, Efficacy, Safety and Costs; Project B) Kinetics of Virological Response.
Hepatitis C virus (HCV) infection provokes thousands of deaths every year all over the world, being the major cause of progressive liver disease, primary hepatic cancer and liver transplantation. Today, a "curative" therapy is available, that can eradicate the viral infection and determine the regression of liver fibrosis, also in cirrhotic subjects.
The current standard-of-care for HCV chronic infection is combination therapy with peginterferon (P-IFN) and ribavirin (RBV). However, this treatment is not only expensive but determines several side effects, that can reduce drug tolerance and hence, patient adherence to therapy. There are two types of available P-IFN on the market: P-IFN alfa-2a (Pegasys®, F.Hoffmann-La Roche) administered at a flat-dose of 180 mcg/week and P-IFN alfa-2b (PegIntron®, Schering-Plough) given at a weight-based dose of 50 to 150 mcg/week. Since only a single amino acid differentiates these types of IFN, administration strategies depend on their pegilation with molecules of 40 or 12kDa, respectively, that accounts for differences in the pharmacokinetic and pharmacodynamic drug-profile and influences probably also bioactivity. No comparative data are available on the benefits and costs of the licensed Peg-IFN plus RBV for the treatment of HCV infection in the real clinical practice, even if, the benefit and favourable cost-efficacy of this antiviral therapy is well established and of large consensus. Recently, the first randomized controlled mega-trial to compare antiviral therapeutic efficacy in naïve patients with HCV-genotype 1 infection during different regimens of P-IFN alfa-2b (at low and standard-dose) and P-IFN alfa-2a plus RBV, has been published, confirming a similar efficacy, of around 40%, obtained with the three schedules evaluated.
Read more
In Italy, a regional program on the Surveillance and Control of HCV Infection, set up by the Regional Health Councillorship, has led to the development of a clinical and epidemiological observatory, constituted by a network of liver tertiary centres (Hepatological Cooperative Network of Veneto, HepCoVe). This collaborative group is connected on-line by a common database that, since 2003, has prospectively collected data on a cohort of more than 3000 patients with chronic HCV infection and, among them, of 506 naïve subjects that consecutively underwent combination therapy with P-IFN alfa-2a or alfa-2b plus RBV.
The aim of this study was to rationalize and improve the social regional health program on antiviral treatment of chronic hepatitis C by assessing the different schedules utilization of P-IFN plus RBV as well as the respective therapeutic effectiveness, safety and costs in the real clinical practice (Project A).
Read the detailed description
(Project B) To evaluate the viral kinetic decay during antiviral combination therapy with P-IFN alfa-2a and 2b type plus ribavirin.
- Conditions
- Hepatitis C Virus, Chronic Liver Disease, Viral Hepatitis, Therapeutic Uses, Antiviral Agents
- Being tested
- peginterferon plus ribavirin
- Keywords
- peginterferon alfa 2a and 2b type, ribavirin, chronic hepatitis C, antiviral therapy cost/efficacy, viral kinetics
- Medical subject headings
- Hepatitis C, Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
peginterferon plus ribavirinDrug
Also called Pegasys, PegIntron, Copegus, Rebetol
peginterferon alfa-2a at 180ug/week (preempt syringe, sc) or peginterferon alfa-2b at 1,5 ug/kg/week (standard dose) or at 1,0 ug/kg/week (lower dose)(preempt pen, sc) for 24 or 48 week in relation to HCV genotype plus ribavirin (capsules, po) at 15mg/kg/daily combination therapy.
| Study group | Role | What they receive |
|---|---|---|
| peginterferon alfa-2a plus ribavirin | Active comparator | patients will receive a fixed dose of 180ug/week of peginterferon alfa-2a plus ribavirin at 15mg/kg/daily. Receives: Drug: peginterferon plus ribavirin |
| peginterferon alfa-2b plus ribavirin | Active comparator | patients will receive a weight adjusted dose (1,5ug/kg) from 50 to 150ug/week of peginterferon alfa-2b (standard dose) or a lower dose (1,0ug/kg) at physician discretion (randomization list available only for 100 cases) plus ribavirin at 15mg/kg/daily. Receives: Drug: peginterferon plus ribavirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of real dose drugs intake in relation to sustained virological response (SVR).
Project A) The analysis will describe the efficacy (SVR) and costs of the 3 different antiviral schedules proposed.
Measured: Measurement of HCV-RNA at 24° week after therapy withdrawal.
Secondary outcomes (1)
Description of the profile of the virus decay during antiviral therapy in relation to virological response.
Project B) The analysis will evaluate the kinetics of virological response obtained with the two peginterferons plus ribavirin by HCV-RNA quantification (Cobas,TaqMan, Roche) at basal time and at 1°,4°,12°,24°,36°,48° week during therapy and at 24° week after therapy withdrawal.
Measured: Measurement of HCV-RNA during therapy in relation to negativity at 24° week after therapy withdrawal.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Sep 2010 (estimated)
- Study startSep 2005
- Primary completionDec 2009
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatitis C VirusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 506 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera di Padova
- Sponsor type
- University, hospital or other
- Collaborators
- Regione Veneto, University of Padova
- Investigators
- liliana chemello, M.D., Ph.D., Study chair, University of Padovaluisa cavalletto, M.D., Ph.D., Principal investigator, Azienda Ospedaliera di Padova
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01195181
- Sponsor's protocol ID
- HEPCOVE protocol
- Other IDs
- DRG N.2920/2002
- Status last verified
- Sep 2010
- First submitted
- 31 Aug 2010
- Last updated
- 6 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Alberti A, Chemello L. and Benvegnù L. Natural history of hepatitis C. J Hepatol. 1999;31:17. Stroffolini T, Andreone P, Andriulli A et al. Characteristics of hepatocellular carcinoma in Italy. J Hepatol. 1998;29:944. Veldt BJ, Heathcote EJ, Wedemeyer H, et al. Sustained virological response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Inter Med. 2007;147:677. Russo MW. and Fried MW. Side effects of therapy for chronic hepatitis C. Gastroenterology 2003;124:1711. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon-alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001; 358: 958. Caliceti P. Pharmacokinetics of pegylated interferons: What is misleading? Dig Liver Dis. 2004;36:S334. Di Bisceglie AM, Ghalib RH, Hamzeh FM. and Rustgi VK. Early virologic response after peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin treatment in patients with chronic hepatitis C. J Viral Hepatitis. 2007;14:721. Malone DC, Tran TT. and Poordad FF. Cost-efficacy analysis of peginterferon alfa-2b plus ribavirin compared with peginterferon alfa-2a plus ribavirin for the treatment of chronic hepatitis C. J Manag Care Pharm. 2005;11: 687. McHutchinson JG, Lawitz EJ, Shiffman ML, for the IDEAL Study Team. Peginterferon Alfa-2b or Alfa-2a with Ribavirin for treatment of hepatitis C infection. NEJM 2009;361(6):580. Hadziyannis SJ, Sette H.Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;2;140(5):346.
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improvement of the Surveillance and Control of Liver Disease and Complication Due to Chronic Hepatitis C: Project A) Antiviral Drugs Use, Efficacy, Safety and Costs; Project B) Kinetics of Virological Response.
- ClinicalTrials.gov ID
- NCT01195181
- Acronym / sponsor ID
- HEPCOVE protocol
- Conditions
- Hepatitis C Virus, Chronic Liver Disease, Viral Hepatitis, Therapeutic Uses, Antiviral Agents
- Keywords
- peginterferon alfa 2a and 2b type, ribavirin, chronic hepatitis C, antiviral therapy cost/efficacy, viral kinetics
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 506 participants (actual)
- Lead sponsor
- Azienda Ospedaliera di PadovaUniversity, hospital or other
- Collaborators
- Regione Veneto, University of Padova
- Study start
- Sep 2005
- Primary completion
- Dec 2009 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 6 Sep 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hepatitis C virus (HCV) infection provokes thousands of deaths every year all over the world, being the major cause of progressive liver disease, primary hepatic cancer and liver transplantation. Today, a "curative" therapy is available, that can eradicate the viral infection and determine the regression of liver fibrosis, also in cirrhotic subjects.
The current standard-of-care for HCV chronic infection is combination therapy with peginterferon (P-IFN) and ribavirin (RBV). However, this treatment is not only expensive but determines several side effects, that can reduce drug tolerance and hence, patient adherence to therapy. There are two types of available P-IFN on the market: P-IFN alfa-2a (Pegasys®, F.Hoffmann-La Roche) administered at a flat-dose of 180 mcg/week and P-IFN alfa-2b (PegIntron®, Schering-Plough) given at a weight-based dose of 50 to 150 mcg/week. Since only a single amino acid differentiates these types of IFN, administration strategies depend on their pegilation with molecules of 40 or 12kDa, respectively, that accounts for differences in the pharmacokinetic and pharmacodynamic drug-profile and influences probably also bioactivity. No comparative data are available on the benefits and costs of the licensed Peg-IFN plus RBV for the treatment of HCV infection in the real clinical practice, even if, the benefit and favourable cost-efficacy of this antiviral therapy is well established and of large consensus. Recently, the first randomized controlled mega-trial to compare antiviral therapeutic efficacy in naïve patients with HCV-genotype 1 infection during different regimens of P-IFN alfa-2b (at low and standard-dose) and P-IFN alfa-2a plus RBV, has been published, confirming a similar efficacy, of around 40%, obtained with the three schedules evaluated.
In Italy, a regional program on the Surveillance and Control of HCV Infection, set up by the Regional Health Councillorship, has led to the development of a clinical and epidemiological observatory, constituted by a network of liver tertiary centres (Hepatological Cooperative Network of Veneto, HepCoVe). This collaborative group is connected on-line by a common database that, since 2003, has prospectively collected data on a cohort of more than 3000 patients with chronic HCV infection and, among them, of 506 naïve subjects that consecutively underwent combination therapy with P-IFN alfa-2a or alfa-2b plus RBV.
The aim of this study was to rationalize and improve the social regional health program on antiviral treatment of chronic hepatitis C by assessing the different schedules utilization of P-IFN plus RBV as well as the respective therapeutic effectiveness, safety and costs in the real clinical practice (Project A).
Detailed description
(Project B) To evaluate the viral kinetic decay during antiviral combination therapy with P-IFN alfa-2a and 2b type plus ribavirin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| peginterferon alfa-2a plus ribavirin | Active comparator | Drug: peginterferon plus ribavirinpatients will receive a fixed dose of 180ug/week of peginterferon alfa-2a plus ribavirin at 15mg/kg/daily. |
| peginterferon alfa-2b plus ribavirin | Active comparator | Drug: peginterferon plus ribavirinpatients will receive a weight adjusted dose (1,5ug/kg) from 50 to 150ug/week of peginterferon alfa-2b (standard dose) or a lower dose (1,0ug/kg) at physician discretion (randomization list available only for 100 cases) plus ribavirin at 15mg/kg/daily. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Naive adult subject
- active HCV infection (HCV-RNA positive)
- histological/biochemical signs of chronic hepatitis or compensated cirrhosis
- willingness of treatment
Key exclusion criteria (7 listed)
- autoimmune disorders
- severe depression or psychiatric disease
- previous decompensation of cirrhosis
- gastroesophageal bleeding
- hepatocellular carcinoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| peginterferon plus ribavirinAlso: Pegasys, PegIntron, Copegus, Rebetolpeginterferon alfa-2a at 180ug/week (preempt syringe, sc) or peginterferon alfa-2b at 1,5 ug/kg/week (standard dose) or at 1,0 ug/kg/week (lower dose)(preempt pen, sc) for 24 or 48 week in relation to HCV genotype plus ribavirin (capsules, po) at 15mg/kg/daily combination therapy. | Drug | peginterferon alfa-2a plus ribavirin, peginterferon alfa-2b plus ribavirin |
Primary outcome
Evaluation of real dose drugs intake in relation to sustained virological response (SVR).
Time frame: Measurement of HCV-RNA at 24° week after therapy withdrawal.
Project A) The analysis will describe the efficacy (SVR) and costs of the 3 different antiviral schedules proposed.
1 secondary outcome
Description of the profile of the virus decay during antiviral therapy in relation to virological response.
Time frame: Measurement of HCV-RNA during therapy in relation to negativity at 24° week after therapy withdrawal.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2010.
- BackgroundAlberti A, Chemello L. and Benvegnù L. Natural history of hepatitis C. J Hepatol. 1999;31:17. Stroffolini T, Andreone P, Andriulli A et al. Characteristics of hepatocellular carcinoma in Italy. J Hepatol. 1998;29:944. Veldt BJ, Heathcote EJ, Wedemeyer H, et al. Sustained virological response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Ann Inter Med. 2007;147:677. Russo MW. and Fried MW. Side effects of therapy for chronic hepatitis C. Gastroenterology 2003;124:1711. Fried MW, Shiffman ML, Reddy KR, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975. Manns MP, McHutchison JG, Gordon SC, et al. Peginterferon-alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001; 358: 958. Caliceti P. Pharmacokinetics of pegylated interferons: What is misleading? Dig Liver Dis. 2004;36:S334. Di Bisceglie AM, Ghalib RH, Hamzeh FM. and Rustgi VK. Early virologic response after peginterferon alpha-2a plus ribavirin or peginterferon alpha-2b plus ribavirin treatment in patients with chronic hepatitis C. J Viral Hepatitis. 2007;14:721. Malone DC, Tran TT. and Poordad FF. Cost-efficacy analysis of peginterferon alfa-2b plus ribavirin compared with peginterferon alfa-2a plus ribavirin for the treatment of chronic hepatitis C. J Manag Care Pharm. 2005;11: 687. McHutchinson JG, Lawitz EJ, Shiffman ML, for the IDEAL Study Team. Peginterferon Alfa-2b or Alfa-2a with Ribavirin for treatment of hepatitis C infection. NEJM 2009;361(6):580. Hadziyannis SJ, Sette H.Jr, Morgan TR, et al. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;2;140(5):346.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
liliana chemello, M.D., Ph.D. study chair
University of Padova
luisa cavalletto, M.D., Ph.D. principal investigator
Azienda Ospedaliera di Padova
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing peginterferon plus ribavirin in people with Hepatitis C Virus and Chronic Liver Disease, run by Azienda Ospedaliera di Padova at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of real dose drugs intake in relation to sustained virological response (SVR). (time frame: Measurement of HCV-RNA at 24° week after therapy withdrawal.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01195181, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2010.