Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin and Patient Support Program in Patients With Chronic Hepatitis C (3DUTCH)

Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin in Patients With Chronic Hepatitis C - An Observational Study in The Netherlands (3DUTCH)

The interferon-free combination regimen of paritaprevir/r - ombitasvir with or without dasabuvir (ABBVIE REGIMEN) ± ribavirin (RBV) for the treatment of chronic hepatitis C (CHC) has been shown to be safe and effective in randomized controlled clinical trials with strict inclusion and exclusion criteria under well controlled conditions.

This observational study is the first effectiveness research examining the ABBVIE REGIMEN ± RBV, used according to local label, under real world conditions in the Netherlands in a clinical practice patient population.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C

• Study Type: Observational
• Enrollment (Actual): 51

Contacts and Locations

Study Locations

• Netherlands
  • Alkmaar, Netherlands, 1815 JD
    • Noordwest Ziekenhuisgroep /ID# 152604
  • Amsterdam, Netherlands, 1061 AE
    • Duplicate_Onze Lieve Vrouwe Gasthuis /ID# 152600
  • Groningen, Netherlands, 9713 GZ
    • Universitair Medisch Centrum Groningen /ID# 152596
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum /ID# 154637
  • Nijmegen, Netherlands, 6526 GA
    • Radbound University Medical Ce /ID# 152598
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medisch Centrum /ID# 154635
  • Rotterdam, Netherlands, 3079 DZ
    • Maasstad Ziekenhuis /ID# 152592
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht /ID# 152595
  • Zuid-Holland
    • Dordrecht, Zuid-Holland, Netherlands, 3318 AT
      • Albert Schweitzer Ziekenhuis /ID# 152597

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Adult patients chronically infected with HCV, receiving the interferon-free ABBVIE REGIMEN will be offered the opportunity to participate in this study during a routine clinical visit at the participating sites.

Description

Inclusion Criteria:

• Treatment-naïve or -experienced adult male or female participants with confirmed CHC, genotype 1 or 4, receiving combination therapy with the interferon-free ABBVIE REGIMEN ± RBV according to standard of care and in line with the current local label.
• If RBV is co-administered with the ABBVIE REGIMEN, it has been prescribed in line with the current local label (with special attention to contraception requirements and contraindication during pregnancy).
• Participants must voluntarily sign and date informed consent prior to inclusion into the study

Exclusion Criteria:

• Patients participating or intending to participate in a concurrent interventional therapeutic trial.
• Unable to complete the questionnaires due to cognitive impairment or lack of any kind of cognitive competence, as to be judged by the healthcare professional who is treating the patient.
• Unable to complete the questionnaires due to language incompetence.
• Unable to voluntarily sign and date the informed consent.

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, 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. Participants with missing HCV RNA were counted as virological failure.	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.
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
Percentage of Participants With Sufficient Follow-up 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 the ABBVIE REGIMEN; 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 the ABBVIE REGIMEN 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 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);; Premature treatment discontinuation with no on-treatment virologic 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)
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 Adverse Events, Serious Adverse Events, or Pregnancies		From first dose of study drug through 30 days after last dose (16 weeks).
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

Collaborators and Investigators

• Sponsor: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2016
• Primary Completion (Actual): March 7, 2018
• Study Completion (Actual): March 7, 2018

Study Registration Dates

• First Submitted: June 27, 2016
• First Submitted That Met QC Criteria: June 27, 2016
• First Posted (Estimate): June 29, 2016

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Observational Study; Chronic Hepatitis C; Chronic Hepatitis C genotype 1; Chronic Hepatitis C genotype 4; Sustained Virological Response; Paritaprevir/r - Ombitasvir, ± 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: P15-788

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