Hepatitis C, Chronic
Conditions
Brief summary
To study retreatment in patients who failed prior treatment with interferon alpha (pegylated or non-pegylated) with or without ribavirin in a real-life setting in an observational/noninterventional study.
Detailed description
This is an observational/non interventional study to collect data on the patient characteristics of those seeking retreatment as well as safety and efficacy information during the first 12 weeks of retreatment.
Interventions
BIOLOGICALPeginterferon alpha
Peginterferon alpha given in combination with ribavirin according to local labeling guidelines
DRUGRibavirin
Ribavirin given in combination with peginterferon alpha according to local labeling guidelines
Sponsors
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C of any genotype; * Prior treatment with interferon alpha (pegylated or non-pegylated) with or without ribavirin did not result in a sustained virological response; * Inclusion criteria listed on the approved label in each country; * Willingness of the patient to participate and sign the Informed Consent Form.
Exclusion criteria
* Patient exclusion from this observational/non-interventional study will be determined by the treating physician and will be based on the local label in each country.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Serious Adverse Events (SAEs) and/or Clinically Significant Adverse Events (AEs) | Up to 12 Weeks | An AE was any untoward medical occurrence in a participant administered a medicinal product which did not necessarily have a causal relationship to the treatment. All AEs reported in the study were judged by the investigator to be clinically significant. An SAE was any adverse drug experience that resulted in death, was life-threatening, caused or prolonged hospitalization, caused persistent or significant disability or incapacity, caused a congenital anomaly or birth defect, or may have required medical or surgical intervention to prevent one of these outcomes. |
| Incidence of Thrombocytopenia | Up to 12 Weeks | Thrombocytopenia is a low blood platelet count |
| Incidence of Treatment Discontinuations Due to Adverse Events | Up to 12 Weeks | All treatment discontinuations due to an AE were reported. See Outcome Measure 1 for definition of AEs. |
| Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | Up to 12 Weeks | All treatment discontinuations due to particular AEs were reported. These discontinuations included treatment stopped (TS) and dose reduced followed by treatment stopped (DR/TS). The particular AE evaluated were anemia (low red blood cells), leucopenia (low white blood cells), neutropenia (low blood neutrophils), thrombocytopenia (low blood platelets), esophageal varices (dilated veins in lower esophagus), splenomegaly (enlarged spleen), portal hypertensive gastropathy (changes in stomach mucosa), and hepatomegaly (enlarged liver) |
| Incidence of Dose Modifications Due to Adverse Events | Up to 12 Weeks | All dose modifications due to an AE were reported. See Outcome Measure 1 for definition of AEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Achieve Undetectable Hepatitis C Virus Ribonucleic Acid (HCV-RNA) | Week 12 | Participant's blood was tested for HCV-RNA by quantitative polymerase chain reaction. The limit of detection for the assay was 50 IU/mL. |
Participant flow
Recruitment details
First participant enrolled: 9 February 2009; last participant completed: 17 October 2011. The study was conducted in 117 centers in 12 countries.
Participants by arm
| Arm | Count |
|---|---|
| Peginterferon Alpha and Ribavirin Peginterferon alpha and ribavirin was administered at the discretion of the treating physician, in accordance per label according to local guidelines for all participating countries. | 963 |
| Total | 963 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 17 |
| Overall Study | Lost to Follow-up | 18 |
| Overall Study | No reason reported | 31 |
| Overall Study | Status unknown | 16 |
Baseline characteristics
| Characteristic | Peginterferon Alpha and Ribavirin |
|---|---|
| Age, Continuous | 50 years |
| Previous non-response type Null responder | 346 participants |
| Previous non-response type Previous non-response type not known | 6 participants |
| Previous non-response type Relapse | 544 participants |
| Previous non-response type Virologic breakthrough | 67 participants |
| Sex: Female, Male Female | 420 Participants |
| Sex: Female, Male Male | 543 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 211 / 963 |
| serious Total, serious adverse events | 18 / 963 |
Outcome results
Primary
Incidence of Dose Modifications Due to Adverse Events
All dose modifications due to an AE were reported. See Outcome Measure 1 for definition of AEs.
Time frame: Up to 12 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha and Ribavirin | Incidence of Dose Modifications Due to Adverse Events | Dose Reduced | 9.7 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Dose Modifications Due to Adverse Events | Dose Reduced, then Treatment Stopped | 0.1 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Dose Modifications Due to Adverse Events | Dose Reduced, Treatment Suspended and Restarted | 0.3 percentage of participants |
Primary
Incidence of Particular Adverse Events Resulting in Treatment Discontinuation
All treatment discontinuations due to particular AEs were reported. These discontinuations included treatment stopped (TS) and dose reduced followed by treatment stopped (DR/TS). The particular AE evaluated were anemia (low red blood cells), leucopenia (low white blood cells), neutropenia (low blood neutrophils), thrombocytopenia (low blood platelets), esophageal varices (dilated veins in lower esophagus), splenomegaly (enlarged spleen), portal hypertensive gastropathy (changes in stomach mucosa), and hepatomegaly (enlarged liver)
Time frame: Up to 12 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | TS - Anemia | 0.6 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | TS - Leucopenia | 0.2 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | TS - Neutropenia | 0.2 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | TS - Thrombocytopenia | 0.1 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | TS - Esophageal varices | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | TS - Splenomegaly | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | TS -Portal hypertensive gastropathy | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | TS - Hepatomegaly | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | DR/TS - Anemia | 0.1 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | DR/TS - Leucopenia | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | DR/TS - Neutropenia | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | DR/TS - Thrombocytopenia | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | DR/TS - Esophageal varices | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | DR/TS - Splenomegaly | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | DR/TS - Portal hypertensive gastropathy | 0.0 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Particular Adverse Events Resulting in Treatment Discontinuation | DR/TS - Hepatomegaly | 0.0 percentage of participants |
Primary
Incidence of Serious Adverse Events (SAEs) and/or Clinically Significant Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant administered a medicinal product which did not necessarily have a causal relationship to the treatment. All AEs reported in the study were judged by the investigator to be clinically significant. An SAE was any adverse drug experience that resulted in death, was life-threatening, caused or prolonged hospitalization, caused persistent or significant disability or incapacity, caused a congenital anomaly or birth defect, or may have required medical or surgical intervention to prevent one of these outcomes.
Time frame: Up to 12 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha and Ribavirin | Incidence of Serious Adverse Events (SAEs) and/or Clinically Significant Adverse Events (AEs) | Clinically significant adverse event | 33.6 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Serious Adverse Events (SAEs) and/or Clinically Significant Adverse Events (AEs) | Serious adverse event | 1.9 percentage of participants |
Primary
Incidence of Thrombocytopenia
Thrombocytopenia is a low blood platelet count
Time frame: Up to 12 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha and Ribavirin | Incidence of Thrombocytopenia | 3.8 percentage of participants |
Primary
Incidence of Treatment Discontinuations Due to Adverse Events
All treatment discontinuations due to an AE were reported. See Outcome Measure 1 for definition of AEs.
Time frame: Up to 12 Weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Peginterferon Alpha and Ribavirin | Incidence of Treatment Discontinuations Due to Adverse Events | Treatment stopped - any AE | 2.6 percentage of participants |
| Peginterferon Alpha and Ribavirin | Incidence of Treatment Discontinuations Due to Adverse Events | Dose reduced, then treatment stopped - any AE | 0.1 percentage of participants |
Secondary
Proportion of Participants Who Achieve Undetectable Hepatitis C Virus Ribonucleic Acid (HCV-RNA)
Participant's blood was tested for HCV-RNA by quantitative polymerase chain reaction. The limit of detection for the assay was 50 IU/mL.
Time frame: Week 12
Population: The population analyzed was 920 participants who received at least 1 dose of study drug and had data collected at the Week 12 visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Peginterferon Alpha and Ribavirin | Proportion of Participants Who Achieve Undetectable Hepatitis C Virus Ribonucleic Acid (HCV-RNA) | 42.4 percentage of participants |