Hepatitis C, Hepatitis C, Chronic
Conditions
Brief summary
The objective of the study is to evaluate the rates of Hepatitis C virus (HCV) eradication and relapse in participants treated with PegIntron and Rebetol in clinical practice in Greece. Participants will not be treated as part of the study. Data on participants treated in accordance with approved labeling will be collected retrospectively from approximately 30 sites in Greece.
Interventions
BIOLOGICALPegIntron (peginterferon alfa-2b, pegylated interferon alfa-2b)
Prior to enrollment in the study, PegIntron was to be administered at a dose of 1.5 μg/kg/week subcutaneously in accordance with approved labeling. Therapy duration varied from 24 to 48 weeks depending on HCV viral load and genotype followed by a 24-week post-treatment follow-up.
Prior to enrollment in the study, Rebetol was to be administered at a dose of 800-1200 mg/day orally in accordance with approved labeling. Therapy duration varied from 24 to 48 weeks depending on HCV viral load and genotype followed by a 24-week post-treatment follow-up.
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants who have already begun Summary of Product Characteristics (SmPC)-based combination treatment with pegylated interferon alpha-2b and ribavirin, prior to the site initiation date. * Participants who have been receiving combination treatment with pegylated interferon alpha-2b and ribavirin for at least 6 months before enrollment. * Participants who have achieved negative HCV RNA at the end of treatment, defined according to genotype (24 weeks for HCV genotypes 2/3 and 48 weeks for genotypes 1/4). * Participants with diagnosed chronic hepatitis C (CHC) and HCV genotype 1, 2, 3 or 4. * Participants older than 18 years, regardless of gender or race.
Exclusion criteria
* The participant has received treatment for CHC in the past (not treatment-naive). * The participant has received treatment in the context of a clinical trial in the participating site. * The participant has been diagnosed with a concomitant infection e.g. with hepatitis B or HIV * The participant has de-compensated liver disease or belongs to a special population, such as liver transplant, hemophilia, severe pre-existing psychiatric disorder, auto-immune disease, thalassaemia. * The participant has positive HCV RNA at the end of treatment. * Pregnant women or women intending to bear children or sexual partners of women wishing to bear children and for a 7-month period after the end of treatment, as indicated in the SmPC of Rebetol. * The participant is not eligible on grounds of contra-indications, special warnings, particular population and/or the section on pregnancy and lactation of the SmPC. * The participant has interrupted treatment for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up | 24 weeks following completion of 24 or 48 weeks of therapy | Sustained virological response (SVR) was assessed at the 24-week post-treatment follow-up (Visit 2). SVR was defined as undetectable plasma Hepatitis C virus Ribonucleic acid (HCV-RNA) at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). |
| Number of Participants Who Demonstrated Virological Relapse as Assessed at 24-week Post-treatment Follow-up | 24 weeks following completion of 24 or 48 weeks of therapy | Virological relapse was assessed at the 24-week post-treatment follow-up (Visit 2). Virological relapse was defined as undetectable plasma HCV-RNA at end of combination treatment (Visit 1- considered Week 24 or Week 48 after treatment start depending on treatment duration), but with positive HCV-RNA at the 24-week post treatment follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline | 24 weeks following completion of 24 or 48 weeks of therapy | SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on HCV-RNA viral load at baseline as assessed by investigator. Low viral load was defined as \<400,000 International Units/milliliter (IU/mL) and high viral load was defined as \>=400,000 IU/mL. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). |
| Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline | 24 weeks following completion of 24 or 48 weeks of therapy | SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on ALT levels at baseline as assessed by investigator. Normal baseline ALT level was defined as \<40 IU/mL and elevated baseline ALT level was defined as \>= 40 IU/mL. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). |
| Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline | 24 weeks following completion of 24 or 48 weeks of therapy | SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on HCV genotype (1, 2, 3, 4, or 2 & 3) at baseline. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). |
| Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response | 24 weeks following completion of 24 or 48 weeks of therapy | SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on achievement of rapid virological response (RVR) where data was available. RVR was defined as negative HCV-RNA after 4 (+/- 1) weeks of treatment. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). |
| Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Compliance With the 80/80/80 Rule | 24 weeks following completion of 24 or 48 weeks of therapy | SVR was assessed by subgroups based on compliance with the 80/80/80 rule where data was available. 80/80/80 compliant participants were those that received \>= 80% of the planned total doses of both pegylated interferon alfa-2b & ribavirin for \>=80% of the duration of therapy. 3 rates were to be computed: Compliance with study duration, compliance with pegylated interferon dose, & compliance with ribavirin dose. A participant was defined as compliant, if none of the 3 rates were \< than 80%. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment. |
| Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Study Treatment Dosage Modification | 24 weeks following completion of 24 or 48 weeks of therapy | SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on study treatment dosage modification: no dosage modification or any dosage modification of study treatment. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). |
| Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline | 24 weeks following completion of 24 or 48 weeks of therapy | SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on liver fibrosis stage, where biopsy was available, at baseline: absence, minimal, moderate, or significant as assessed by investigator. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration). |
Participant flow
Pre-assignment details
401 participants were screened for eligibility. 332 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin Participants with CHC of any genotype were treated with a standard treatment regimen of pegylated interferon alfa-2b and ribavirin. Each dose of pegylated interferon alfa-2b was administered as a subcutaneous injection calculated as 1.5 μg/kg once a week. Ribavirin was taken orally, twice daily, at a daily dose of 800 to 1200 mg. Therapy duration varied from 24 to 48 weeks depending on HCV genotype and viral load followed by a 24-week post-treatment follow-up. | 332 |
| Total | 332 |
Baseline characteristics
| Characteristic | Pegylated Interferon Alpha-2b and Ribavirin |
|---|---|
| Age, Continuous | 39.9 years STANDARD_DEVIATION 11.8 |
| Sex: Female, Male Female | 102 Participants |
| Sex: Female, Male Male | 230 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 123 / 401 |
| serious Total, serious adverse events | 5 / 401 |
Outcome results
Primary
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up
Sustained virological response (SVR) was assessed at the 24-week post-treatment follow-up (Visit 2). SVR was defined as undetectable plasma Hepatitis C virus Ribonucleic acid (HCV-RNA) at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Efficacy Analysis Set (EAS) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up | 286 Participants |
Primary
Number of Participants Who Demonstrated Virological Relapse as Assessed at 24-week Post-treatment Follow-up
Virological relapse was assessed at the 24-week post-treatment follow-up (Visit 2). Virological relapse was defined as undetectable plasma HCV-RNA at end of combination treatment (Visit 1- considered Week 24 or Week 48 after treatment start depending on treatment duration), but with positive HCV-RNA at the 24-week post treatment follow-up.
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Efficacy Analysis Set (EAS) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Demonstrated Virological Relapse as Assessed at 24-week Post-treatment Follow-up | 23 Participants |
Secondary
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on achievement of rapid virological response (RVR) where data was available. RVR was defined as negative HCV-RNA after 4 (+/- 1) weeks of treatment. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. There was missing data for 250 participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response | RVR at Week 4 (+/- 1) | 20 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response | Non-RVR at Week 4 (+/- 1) | 16 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Achievement of Rapid Virological Response | Missing | 250 Participants |
Secondary
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on ALT levels at baseline as assessed by investigator. Normal baseline ALT level was defined as \<40 IU/mL and elevated baseline ALT level was defined as \>= 40 IU/mL. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. There was missing data for 6 participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline | Normal Baseline ALT levels | 28 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline | Elevated Baseline ALT levels | 252 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Alanine Aminotransferase (ALT) Levels at Baseline | Missing | 6 Participants |
Secondary
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Compliance With the 80/80/80 Rule
SVR was assessed by subgroups based on compliance with the 80/80/80 rule where data was available. 80/80/80 compliant participants were those that received \>= 80% of the planned total doses of both pegylated interferon alfa-2b & ribavirin for \>=80% of the duration of therapy. 3 rates were to be computed: Compliance with study duration, compliance with pegylated interferon dose, & compliance with ribavirin dose. A participant was defined as compliant, if none of the 3 rates were \< than 80%. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment.
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: No data had been captured in the Case Report Forms, and therefore no relevant analysis had been performed.
Secondary
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on HCV genotype (1, 2, 3, 4, or 2 & 3) at baseline. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. 23 participants were relapsers.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline | Genotype 1 | 81 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline | Genotype 2 | 28 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline | Genotype 3 | 146 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline | Genotype 4 | 30 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV Genotype at Baseline | Genotype 2 & 3 | 1 Participants |
Secondary
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on HCV-RNA viral load at baseline as assessed by investigator. Low viral load was defined as \<400,000 International Units/milliliter (IU/mL) and high viral load was defined as \>=400,000 IU/mL. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. There was missing data for 32 participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline | Low Viral Load | 99 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline | High Viral Load | 155 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on HCV-RNA Viral Load at Baseline | Missing | 32 Participants |
Secondary
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on liver fibrosis stage, where biopsy was available, at baseline: absence, minimal, moderate, or significant as assessed by investigator. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis. There was missing data for 157 participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline | Absence | 83 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline | Minimal | 27 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline | Moderate | 15 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline | Significant | 4 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Liver Fibrosis Stage at Baseline | Missing | 157 Participants |
Secondary
Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Study Treatment Dosage Modification
SVR was assessed at the 24-week post-treatment follow-up (Visit 2) by subgroups based on study treatment dosage modification: no dosage modification or any dosage modification of study treatment. SVR was defined as undetectable plasma HCV-RNA at 24 weeks after termination of combination treatment (24 or 48 weeks of treatment duration).
Time frame: 24 weeks following completion of 24 or 48 weeks of therapy
Population: Efficacy Analysis Set (N=309) included all participants enrolled into the study who attended the final study visit and had HCV RNA evaluation measurement available at the 24-week post-treatment follow-up. Of the 309 participants in this population, 286 achieved SVR and were included in this analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Study Treatment Dosage Modification | No Dosage Modification of Study Treatment | 234 Participants |
| Pegylated Interferon Alpha-2b and Ribavirin | Number of Participants Who Achieved Sustained Virological Response as Assessed at 24-week Post-treatment Follow-up by Subgroups Based on Study Treatment Dosage Modification | Any Dosage Modification of Study Treatment | 52 Participants |