Effectiveness of Paritaprevir/Ritonavir, Ombitasvir, + Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C in Romania

Study Overview
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Brief Summary
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This study seeks to provide evidence of the effectiveness and obtain patient reported outcome (PRO) data for the interferon-free regimen of paritaprevir (PTV)/ritonavir (r) + ombitasvir (OBV), + dasabuvir (DSV), +/- ribavirin (RBV) in participants with chronic hepatitis C (CHC) in a real life setting across clinical practice patient populations in Romania.

Official Title
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Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, + Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in Romania

Conditions
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Chronic Hepatitis C

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment-naïve or -experienced adult male or female patients with confirmed CHC, genotype 1, receiving combination therapy with the interferon-free paritaprevir/ritonavir and ombitasvir with dasabuvir ± RBV according to standard of care and in line with the current local label If RBV is co-administered with the paritaprevir/ritonavir and ombitasvir with dasabuvir, it has been prescribed in line with the current local label (with special attention to contraception requirements and contraindication during pregnancy) Patients must voluntarily sign and date a patient authorization to use and/or disclose his/her anonymized health data prior to inclusion into the study Patient must not be participating or intending to participate in a concurrent interventional therapeutic trial Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Paritaprevir/Ritonavir + Ombitasvir ± Dasabuvir ± Ribavirin<br>Participants in this observational study received treatment with paritaprevir/ritonavir (r) and ombitasvir with or without dasabuvir ± ribavirin (RBV) for 12 or 24 weeks for the treatment of chronic hepatitis C (CHC), according to hepatitis C virus (HCV) genotype/subtype and stage of liver disease. The prescription of treatment regimen was at the discretion of the physician in accordance with local clinical practice and label, and was made independently from this observational study and preceded the decision to offer the patient the opportunity to participate in this study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Sustained Virological Response 12 Weeks Post-treatment (SVR12) | Sustained virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) levels less than 50 IU/mL 12 weeks after the last dose of study drug. | 12 weeks after the last dose of study drug (week 24 or 36 depending on the treatment regimen) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Virological Response at End of Treatment | Virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) levels less than 50 IU/mL. | End of treatment (week 12 or 24 depending on the treatment regimen) | 
| Percentage of Participants in the Core Population With Sufficient Follow-up Data for SVR12 Who Achieved Sustained Virological Response 12 Weeks Post-treatment | Sustained virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) levels less than 50 IU/mL 12 weeks after the last dose of study drug. The core population with sufficient follow-up data regarding SVR12 included all core population participants who had evaluable HCV RNA data ≥ 70 days after the last actual dose of paritaprevir/ritonavir, ombitasvir and dasabuvir or a HCV RNA value ≥ 50 IU/mL at the last measurement post-baseline or had HCV RNA < 50 IU/mL at the last measurement post-baseline, but no HCV RNA measurement ≥ 70 days after the last actual dose of paritaprevir/ritonavir, ombitasvir with dasabuvir due to reasons related to safety (e.g. dropped out due to adverse event) or virologic failure. | 12 weeks after the last dose of study drug (week 24 or 36 depending on the treatment regimen) | 
| Percentage of Participants With Relapse | Relapse was defined as participants with a virologic response (VR; HCV RNA < 50 IU/mL) at end of treatment (EOT) followed by HCV RNA ≥ 50 IU/mL at any time after the end of treatment. | End of treatment (week 12 or 24 depending on the treatment regimen) and up to 24 weeks after the end of treatment. | 
| Percentage of Participants With Breakthrough | Breakthrough was defined as at least one documented HCV RNA < 50 IU/mL followed by HCV RNA ≥ 50 IU/mL during treatment. | 12 or 24 weeks (depending on the treatment regimen) | 
| Percentage of Participants in Each Non-response Category 12 Weeks Post-treatment | SVR12 non-response was categorized according to the following: On-treatment virologic failure (breakthrough [at least one documented HCV RNA < 50 IU/mL followed by HCV RNA ≥ 50 IU/mL during treatment] or failure to suppress [each measured on-treatment HCV RNA value ≥ 50 IU/mL]); Relapse, defined as HCV RNA < 50 IU/mL at EOT followed by HCV RNA ≥ 50 IU/mL post-treatment in patients who completed treatment (not more than 7 days shortened); Death; Premature treatment discontinuation with no on-treatment virological failure; Missing SVR12 data and/or none of the above criteria. | 12 weeks after the last dose of study drug (week 24 or 36 depending on the treatment regimen) | 
| Assigned Treatment Regimen | Treatment regimen was assigned by the physician according to local practice and label. Participants could receive three direct-acting antiviral (DAA) drugs (paritaprevir/ritonavir, ombitasvir, and dasabuvir) with or without RBV for 12 or 24 weeks. | Baseline | 
| Percentage of the Direct Acting Antiviral (DAA) Dose Taken in Relation to the Target Dose of DAA | Adherence to study treatment was calculated as: Cumulative dose taken / (initial prescribed dose * planned duration) | From first dose of study drug to end of treatment, 12 to 24 weeks depending on the treatment regimen. | 
| Percentage of the Ribavirin Dose Taken in Relation to the Target Dose of Ribavirin | Adherence to study treatment was calculated as: Cumulative dose taken / (initial prescribed dose * planned duration) | From first dose of study drug to end of treatment, 12 to 24 weeks depending on the treatment regimen | 
| Percentage of Ribavirin (RBV) Treatment Days in Relation to the Target Number of Ribavirin Treatment Days |  | From first dose of study drug to end of treatment, 12 to 24 weeks depending on the treatment regimen. | 
| Number of Participants With Comorbidities |  | Baseline | 
| Number of Participants Who Received Concomitant Medications | Concomitant medication other than for chronic hepatitis C used from the time when the decision was made to initiate treatment with paritaprevir/ritonavir and ombitasvir with or without dasabuvir until after the last dose. | From first dose of study drug to end of treatment, 12 to 24 weeks depending on the treatment regimen | 
| Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) Index Score | The EQ-5D-5L is a health state utility instrument that evaluates preference for health status. The 5 items in the EQ-5D-5L comprise 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which are rated on 5 levels of severity (1: indicating no problem, 2: indicating slight problems, 3: indicating moderate problems, 4: indicating severe problems, 5: indicating extreme problems), and a separate visual analog scale (VAS). Responses to the 5 dimension scores were combined and converted into a single preference-weighted health utility index score by applying country-specific weights.The range for EQ-5D-5L index score is 0 to 1 where '0' is defined as a health state equivalent to being dead and '1' is full health.The higher the score the better the health status. | Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment | 
| Change From Baseline in EuroQol 5 Dimension 5 Level (EQ-5D-5L) VAS Score | The EQ-5D-5L is a health state utility instrument that evaluates preference for health status. with a separate visual analog scale (VAS). The VAS assesses overall health on a scale from 0 (worst health imaginable) to 100 (best health imaginable). | Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI): Absenteeism | The WPAI Hepatitis C V2.0 is an HCV specific questionnaire used to measure work absenteeism, work presenteeism, and daily activity impairment. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Absenteeism indicates the percentage of work time missed due to health problems. | Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI): Presenteeism | The WPAI Hepatitis C V2.0 is an HCV specific questionnaire used to measure work absenteeism, work presenteeism, and daily activity impairment. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Presenteeism indicates the percentage of impairment while working due to health problems. | Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI): Total Work Productivity Impairment (TWP) | The WPAI Hepatitis C V2.0 is an HCV specific questionnaire used to measure work absenteeism, work presenteeism, and daily activity impairment. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Total work productivity impairment (TWP) indicates the percentage of overall work impairment due to health problems. | Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment | 
| Change From Baseline in Work Productivity and Activity Impairment (WPAI): Total Activity Impairment | The WPAI Hepatitis C V2.0 is an HCV specific questionnaire used to measure work absenteeism, work presenteeism, and daily activity impairment. Respondents were asked about time missed from work and time while at work during which productivity was impaired in the past seven days. Results of WPAI are expressed as a percentage of impairment from 0 to 100, with higher percentages indicating greater impairment and less productivity. Total activity impairment (TAI) indicates the percentage of general (non-work) activity impairment due to health problems. | Baseline, end of treatment (week 12 or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment | 
| Change From Baseline in Patient Activation Measure 13 (PAM-13) | PAM 13 is a measure used to assess the patient knowledge, skill, and confidence for self-management, consisting of 13 questions. Each of the 13 items can be answered with one of four possible response options, which are disagree strongly (1), disagree (2), agree (3), agree strongly (4). Scores were summed to calculate the overall raw score, then transformed to a scale with a theoretical range 0 to 100, based on calibration tables, with higher PAM scores indicating higher patient activation | Baseline and end of treatment (week 12 or 24 depending on the treatment regimen) | 
| Change From Baseline in Beliefs Medication Questionnaire - (18-item BMQ) | The BMQ consists of 2 sections and 18 questions to screen for patients' beliefs, attitudes and concerns about their medication. The BMQ-Specific section comprises two 5-item subscales assessing the necessity of and concerns about the prescribed medication (Specific-Necessity and Specific-Concerns). The BMQ-General section comprises two 4-item subscales assessing beliefs that medicines are harmful and overused by doctors in general (General-Harm and General-Overuse). The 18 items are rated on a Likert scale from 1 (strongly disagree) to 5 (strongly agree). Each subscale score ranges from 1 to 5. High scores in the Specific-Concerns scale represent the notion that adverse reactions are potentially harmful when taking medication on a regular basis, and high scores in the Specific-Necessity scale indicate the patient's need to adhere to medication to maintain health. High scores in the General-Harm and General-Overuse scales represent an overall negative perception of medication. | Baseline and end of treatment (week 12 or 24 depending on the treatment regimen) | 
| Number of Participants With Adverse Events, Serious Adverse Events, or Pregnancies |  | From first dose of study drug through 30 days after last dose (16 or 28 weeks depending on the treatment regimen). The over all median (minimum, maximum) duration of treatment was 84 (28, 175) days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, Chronic Hepatitis C, Paritaprevir, Ombitasvir, Dasabuvir