Chronic Hepatitis C
Conditions
Brief summary
This observational study will examine the efficacy and safety of pegylated interferon (peginterferon) alfa-2a, mostly in combination with ribavirin treatment in chronic hepatitis C (CHC). Quality of care will also be assessed. Approximately 12% of the interferon-treated CHC patient population in Germany is expected to be studied over a period of 5 years.
Interventions
DRUGPegylated interferon alfa-2a
Pegylated interferon alfa-2a administered according to corresponding summary of product characteristics (SmPC).
DRUGRibavirin
Ribavirin administered according to corresponding summary of product characteristics (SmPC).
Sponsors
Hoffmann-La Roche
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or over * Clinically diagnosed CHC with detectable virus replication * Women of childbearing potential should use adequate contraception. It is important that female participants of childbearing potential and their sexual partners use 2 contraceptive methods at the same time during treatment and 4 months after treatment discontinuation. During this time pregnancy tests have to be performed monthly. Particular attention is also required and pregnancy should be avoided 7 months after treatment discontinuation in female sexual partners of male participants taking ribavirin (Copegus®). Both should use adequate contraception.
Exclusion criteria
* Any contraindications for peginterferon alfa-2a or ribavirin treatment * Pregnant or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Serious Adverse Drug Reactions (SADR) | Up to Week 96 | — |
| Percentage of Participants With Rapid Virologic Response (RVR) | At Week 4 | RVR is defined as Hepatitis C-Virus (HCV) Polymerase Chain Reaction (PCR) assay result qualitatively negative and/or viral load ≤50 International Units/milliliter (IU/ml) at Week 4. |
| Percentage of Participants With Early Virologic Response (EVR) | At Week 12 | EVR is defined as HCV-PCR assay result qualitatively negative and/or decline of viral load of ≥2 log levels and/or viral load ≤50 IU/ml at Week 12. |
| Percentage of Participants With End of Treatment (EOT) Response | Up to Week 72 | EOT Response is defined as HCV-PCR assay result below limit of detection or viral load ≤50 IU/ml and/or qualitatively negative at the end of treatment. |
| Percentage of Participants With Sustained Virologic Response (SVR) | Up to Week 96 | SVR is defined as HCV-PCR assay result below limit of detection or viral load ≤50 IU/ml and/or qualitatively negative at least 12 weeks after the end of treatment at follow up. Follow-up visit occurred at 12 to 24 weeks following discontinuation of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Cumulative Dose of Ribavirin Received | Up to Week 96 | Data for the accumulation of the cumulative dose of ribavirin were analyzed and reported as the percentage of the intended dose participants received. Cumulative doses were evaluated for participants for whom dosage data were documented consistently throughout the observational period. If the treatment was ongoing at the study end, the cumulative dose was aggregated for the documented observational period. |
| Duration of Peginterferon Alfa-2a Therapy | Up to Week 72 | Treatment duration was evaluated for participants for whom dates of treatment start and end of therapy were documented. |
| Percentage of Participants With the Most Frequent Concomitant Medications | At Baseline (Day 1) | Most frequent concomitant medications were defined as those, which were observed in \>1 % of participants. |
| Percentage Cumulative Dose of Peginterferon Alfa-2a Received | Up to Week 96 | Data for the accumulation of the cumulative dose of peginterferon alfa-2a were analyzed and reported as the percentage of the intended dose participants received. Cumulative doses were evaluated for participants for whom dosage data were documented consistently throughout the observational period. If the treatment was ongoing at the study end, the cumulative dose was aggregated for the documented observational period. |
Countries
Germany
Participant flow
Pre-assignment details
Per protocol participants were not allocated to study arms. Separation of participants was performed post hoc for all analyses. Participants who underwent elastography were allocated to separate arms as another time schedule was used and also untreated participants were documented, who were analyzed separately from treated participants.
Participants by arm
| Arm | Count |
|---|---|
| Main Analysis Set Participants with CHC treated with peginterferon alfa-2a monotherapy, or with peginterferon alfa-2a and ribavirin with or without other approved CHC therapy were observed. Treatments were administered according to their corresponding SmPC. | 9,620 |
| Elastography Analysis Set: Treated Participants with CHC treated with peginterferon alfa-2a monotherapy, or with peginterferon alfa-2a and ribavirin with or without other approved CHC therapy were observed. The elastography analysis set includes participants, who underwent elastography and were documented in the fibroscan module. The treated set included those who were treated with HCV treatment as indicated. | 90 |
| Elastography Analysis Set: Untreated The untreated elastography analysis set includes those participants with CHC, who underwent elastography, were documented in the fibroscan module and were not treated with HCV treatment. | 518 |
| Total | 10,228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Change of Laboratory Parameter | 10 | 0 | 0 |
| Overall Study | Concomitant Disease | 74 | 2 | 0 |
| Overall Study | Hospitalization/Surgical Intervention | 6 | 0 | 0 |
| Overall Study | Lack of Compliance | 211 | 7 | 0 |
| Overall Study | Lack of Tolerability | 305 | 3 | 0 |
| Overall Study | Lack of Virological Response | 1,044 | 8 | 0 |
| Overall Study | Lost to Follow-up | 451 | 8 | 0 |
| Overall Study | Patient Died | 19 | 0 | 0 |
| Overall Study | Patients Request | 307 | 9 | 0 |
| Overall Study | Relocation/Change of Physician | 40 | 1 | 0 |
| Overall Study | Unplanned Event | 82 | 2 | 0 |
Baseline characteristics
| Characteristic | Main Analysis Set | Elastography Analysis Set: Treated | Elastography Analysis Set: Untreated | Total |
|---|---|---|---|---|
| Age, Continuous | 42.2 years STANDARD_DEVIATION 11.4 | 44.9 years STANDARD_DEVIATION 10.5 | 51.1 years STANDARD_DEVIATION 12.8 | 42.6 years STANDARD_DEVIATION 11.6 |
| Number of Participants With Each Hepatitis C Viral Genotype Genotype 1 | 5699 participants | 51 participants | 377 participants | 6127 participants |
| Number of Participants With Each Hepatitis C Viral Genotype Genotype 2 | 544 participants | 3 participants | 11 participants | 558 participants |
| Number of Participants With Each Hepatitis C Viral Genotype Genotype 3 | 2903 participants | 30 participants | 89 participants | 3022 participants |
| Number of Participants With Each Hepatitis C Viral Genotype Genotype 4 | 421 participants | 6 participants | 18 participants | 445 participants |
| Number of Participants With Each Hepatitis C Viral Genotype Genotype 5 | 17 participants | 0 participants | 2 participants | 19 participants |
| Number of Participants With Each Hepatitis C Viral Genotype Genotype 6 | 15 participants | 0 participants | 1 participants | 16 participants |
| Number of Participants With Each Hepatitis C Viral Genotype Genotype unknown | 21 participants | 0 participants | 20 participants | 41 participants |
| Number of Participants With Low or High Viral Load High viral load | 5771 participants | 66 participants | 356 participants | 6193 participants |
| Number of Participants With Low or High Viral Load Low viral load | 3769 participants | 24 participants | 139 participants | 3932 participants |
| Number of Participants With Low or High Viral Load Not determined/not assessable | 80 participants | 0 participants | 23 participants | 103 participants |
| Sex: Female, Male Female | 3273 Participants | 23 Participants | 217 Participants | 3513 Participants |
| Sex: Female, Male Male | 6347 Participants | 67 Participants | 301 Participants | 6715 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 5,721 / 9,620 | 82 / 90 | 0 / 518 |
| serious Total, serious adverse events | 439 / 9,620 | 4 / 90 | 0 / 518 |
Outcome results
Primary
Percentage of Participants With Early Virologic Response (EVR)
EVR is defined as HCV-PCR assay result qualitatively negative and/or decline of viral load of ≥2 log levels and/or viral load ≤50 IU/ml at Week 12.
Time frame: At Week 12
Population: Only treated participants were analyzed for this Outcome Measure. In each analysis set only those participants were included for whom a valid HCV PCR result was available or who discontinued from treatment before Week 12.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Analysis Set | Percentage of Participants With Early Virologic Response (EVR) | 71.2 percentage of participants |
| Elastography Analysis Set: Treated | Percentage of Participants With Early Virologic Response (EVR) | 77.8 percentage of participants |
Primary
Percentage of Participants With End of Treatment (EOT) Response
EOT Response is defined as HCV-PCR assay result below limit of detection or viral load ≤50 IU/ml and/or qualitatively negative at the end of treatment.
Time frame: Up to Week 72
Population: Only treated participants were analyzed for this Outcome Measure. All participants within each analysis set were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Analysis Set | Percentage of Participants With End of Treatment (EOT) Response | 59.2 percentage of participants |
| Elastography Analysis Set: Treated | Percentage of Participants With End of Treatment (EOT) Response | 51.1 percentage of participants |
Primary
Percentage of Participants With Rapid Virologic Response (RVR)
RVR is defined as Hepatitis C-Virus (HCV) Polymerase Chain Reaction (PCR) assay result qualitatively negative and/or viral load ≤50 International Units/milliliter (IU/ml) at Week 4.
Time frame: At Week 4
Population: Only treated participants were analyzed for this Outcome Measure. In each analysis set only those participants were included for whom a valid HCV PCR result was available or who discontinued from treatment before Week 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Analysis Set | Percentage of Participants With Rapid Virologic Response (RVR) | 40.0 percentage of participants |
| Elastography Analysis Set: Treated | Percentage of Participants With Rapid Virologic Response (RVR) | 41.7 percentage of participants |
Primary
Percentage of Participants With Serious Adverse Drug Reactions (SADR)
Time frame: Up to Week 96
Population: Only treated participants were analyzed for this Outcome Measure. All participants within each analysis set were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Analysis Set | Percentage of Participants With Serious Adverse Drug Reactions (SADR) | 3.5 percentage of participants |
| Elastography Analysis Set: Treated | Percentage of Participants With Serious Adverse Drug Reactions (SADR) | 3.3 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response (SVR)
SVR is defined as HCV-PCR assay result below limit of detection or viral load ≤50 IU/ml and/or qualitatively negative at least 12 weeks after the end of treatment at follow up. Follow-up visit occurred at 12 to 24 weeks following discontinuation of treatment.
Time frame: Up to Week 96
Population: Only treated participants were analyzed for this Outcome Measure. All participants within each analysis set were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Main Analysis Set | Percentage of Participants With Sustained Virologic Response (SVR) | 41.4 percentage of participants |
| Elastography Analysis Set: Treated | Percentage of Participants With Sustained Virologic Response (SVR) | 36.7 percentage of participants |
Secondary
Duration of Peginterferon Alfa-2a Therapy
Treatment duration was evaluated for participants for whom dates of treatment start and end of therapy were documented.
Time frame: Up to Week 72
Population: Only treated participants were analyzed for this Outcome Measure. Only participants with evaluable data for this Outcome Measure were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Analysis Set | Duration of Peginterferon Alfa-2a Therapy | 27.3 weeks |
| Elastography Analysis Set: Treated | Duration of Peginterferon Alfa-2a Therapy | 29.3 weeks |
Secondary
Percentage Cumulative Dose of Peginterferon Alfa-2a Received
Data for the accumulation of the cumulative dose of peginterferon alfa-2a were analyzed and reported as the percentage of the intended dose participants received. Cumulative doses were evaluated for participants for whom dosage data were documented consistently throughout the observational period. If the treatment was ongoing at the study end, the cumulative dose was aggregated for the documented observational period.
Time frame: Up to Week 96
Population: Only treated participants were analyzed for this Outcome Measure. Only participants with evaluable data for this Outcome Measure were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Analysis Set | Percentage Cumulative Dose of Peginterferon Alfa-2a Received | 97.9 percentage of cumulated dose |
| Elastography Analysis Set: Treated | Percentage Cumulative Dose of Peginterferon Alfa-2a Received | 94.8 percentage of cumulated dose |
Secondary
Percentage Cumulative Dose of Ribavirin Received
Data for the accumulation of the cumulative dose of ribavirin were analyzed and reported as the percentage of the intended dose participants received. Cumulative doses were evaluated for participants for whom dosage data were documented consistently throughout the observational period. If the treatment was ongoing at the study end, the cumulative dose was aggregated for the documented observational period.
Time frame: Up to Week 96
Population: Only treated participants were analyzed for this Outcome Measure. Only participants with evaluable data for this Outcome Measure were included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Main Analysis Set | Percentage Cumulative Dose of Ribavirin Received | 100.00 percentage of cumulated dose |
| Elastography Analysis Set: Treated | Percentage Cumulative Dose of Ribavirin Received | 97.92 percentage of cumulated dose |
Secondary
Percentage of Participants With the Most Frequent Concomitant Medications
Most frequent concomitant medications were defined as those, which were observed in \>1 % of participants.
Time frame: At Baseline (Day 1)
Population: Only main analysis set had evaluable data for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Thyroid hormones | 1.8 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Non-selective monoamine reuptake inhibitors | 1.2 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Anilides | 10.6 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Selective serotonin reuptake inhibitors | 9.9 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Proton pump inhibitors | 5.3 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Propionic acid derivatives | 4.7 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Propulsives | 2.3 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Other antidepressants | 2.3 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Angiotensin-converting-enzyme (ACE) inhibitors | 2.0 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Corticosteroids, potent (group III) | 1.7 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Benzodiazepine related drugs | 1.5 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Pyrazolones | 1.4 percentage of participants |
| Main Analysis Set | Percentage of Participants With the Most Frequent Concomitant Medications | Beta blocking agents, selective | 1.3 percentage of participants |