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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C

• Study Type: Observational
• Enrollment (Actual): 522

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Clinical practice patient populations with chronic infection of HCV Genotype 1 (GT1)

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Paritaprevir/Ritonavir + Ombitasvir ± Dasabuvir ± Ribavirin; 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?

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 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.
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 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
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 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
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 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
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 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.

Collaborators and Investigators

• Sponsor: AbbVie
• Collaborators: IST GmbH, Germany

Publications and helpful links

General Publications

• Ferenci P, Bourgeois S, Buggisch P, Norris S, Curescu M, Larrey D, Marra F, Kleine H, Dorr P, Charafeddine M, Crown E, Bondin M, Back D, Flisiak R. Real-world safety and effectiveness of ombitasvir/paritaprevir/ritonavir +/- dasabuvir +/- ribavirin in hepatitis C virus genotype 1- and 4-infected patients with diverse comorbidities and comedications: A pooled analysis of post-marketing observational studies from 13 countries. J Viral Hepat. 2019 Jun;26(6):685-696. doi: 10.1111/jvh.13080. Epub 2019 Mar 5.

Helpful Links

• Related info

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2016
• Primary Completion (Actual): August 4, 2017
• Study Completion (Actual): August 4, 2017

Study Registration Dates

• First Submitted: June 16, 2016
• First Submitted That Met QC Criteria: June 16, 2016
• First Posted (Estimate): June 21, 2016

Study Record Updates

• Last Update Posted (Actual): January 25, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: HCV; Chronic Hepatitis C; Ombitasvir; Paritaprevir; Dasabuvir
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic
• Other Study ID Numbers: P15-698

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No