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

Real World Evidence of the Effectiveness of Paritaprevir/r - Ombitasvir, ± Dasabuvir, ± Ribavirin and Patient Support Program in Patients With Chronic Hepatitis C - An Observational Study in Israel (CITRINE STUDY)

The interferon-free combination regimen of ombitasvir/paritaprevir/ritonavir/ 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 was the first effectiveness research examining the ABBVIE REGIMEN ± RBV, used according to local label, under real world conditions in Israel in a clinical practice patient population.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: Ombitasvir/paritaprevir/ritonavir; Drug: Dasabuvir; Drug: Ribavirin; Behavioral: Patient support program

Detailed Description

This was a prospective, multi-center observational study in participants receiving the interferon-free ABBVIE REGIMEN ± RBV in Israel. The prescription of a 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 participant the opportunity to participate in this study. Adults chronically infected with HCV, receiving the interferon-free ABBVIE REGIMEN, were offered the opportunity to participate in this study during a routine clinical visit at the participating sites. Follow-up visits, treatment, procedures, and diagnostic methods followed physicians' routine clinical practice. Data were collected at the following time windows: baseline, early on-treatment visit, mid-treatment visit (for participants with a treatment duration of 24 weeks), end of treatment (EoT), early post-treatment and 12 and 24 weeks after the end of treatment (representing sustained virologic response 12 weeks after the end of treatment [SVR12] and sustained virologic response 24 weeks after the end of treatment [SVR24]).

• Study Type: Observational
• Enrollment (Actual): 256

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel, 18341
    • Ha'Emek Medical Center /ID# 153695
  • Be'er Sheva, Israel, 84101
    • Soroka Medical Ctr /ID# 153697
  • Be'er Ya'akov, Israel, 70300
    • Assaf Harofeh Medical Center /ID# 153708
  • Gush Dan, Israel, 7565016
    • Maccabi Health Services /ID# 158647
  • Hadera, Israel, 38100
    • Hillel Yaffe Medical Center /ID# 153702
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 153694
  • Haifa, Israel, 3339419
    • Bnai Zion Medical Center /ID# 153700
  • Haifa, Israel, 3436212
    • The Lady Davis Carmel MC /ID# 153692
  • Holon, Israel, 58100
    • The Edith Wolfson Medical Cent /ID# 153706
  • Jerusalem, Israel, 91031
    • Shaare Zedek Medical Center /ID# 153699
  • Jerusalem, Israel, 91120
    • Hadassah /ID# 153701
  • Kfar Saba, Israel, 44281
    • Meir Medical Center /ID# 153698
  • Nahariya, Israel, 22100
    • Western Galilee Medical Center /ID# 153705
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center /ID# 153707
  • HaDarom
    • Be'er Sheva, HaDarom, Israel, 84101
      • Soroka Medical Center /ID# 169357
  • Tel-Aviv
    • Petakh Tikva, Tel-Aviv, Israel, 4941492
      • Rabin Medical Center /ID# 153696
    • Petakh Tikva, Tel-Aviv, Israel, 4941492
      • Rabin Medical Center /ID# 158648
    • Tel Aviv-Yafo, Tel-Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Ctr /ID# 153693

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

Participants with chronic hepatitis C virus infection, genotype 1 or 4, receiving combination therapy with the interferon-free ABBVIE REGIMEN ± ribavirin.

Description

• Treatment-naïve or -experienced adult male or female participants with confirmed chronic hepatitis C (CHC), genotype 1 or 4, receiving combination therapy with the interferon-free ABBVIE REGIMEN ± ribavirin (RBV) according to standard of care and in line with the current local label
• If RBV was co-administered with the ABBVIE REGIMEN, it had to be prescribed in line with the current local label (with special attention to contraception requirements and contraindication during pregnancy)
• Participants had to voluntarily sign and date an informed consent form prior to inclusion into the study
• Participants must not have participated or intended 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

Intervention / Treatment

Participants with HCV genotype 1 or 4; Ombitasvir/paritaprevir/ritonavir (two 12.5 mg/75 mg/50 mg co-formulated tablets once daily); ± dasabuvir (tablet; 250 mg twice daily); ± weight-based ribavirin (tablets; 1000 or 1200 mg divided twice a day) up to 24 weeks

Drug: Ombitasvir/paritaprevir/ritonavir; Co-formulated tablet; Other Names: Ombitasvir also known as ABT-267; Paritaprevir also known as ABT-450; Drug: Dasabuvir; Tablet; Other Names: ABT-333; Drug: Ribavirin; Tablet; Behavioral: Patient support program; Supportive services provided to participants included reminder calls, emails, text messages, a Care Coach, and educational/informational materials.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12)	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL 12 weeks after the last actual dose of study drug.	12 weeks after the last actual dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Viral Breakthrough	Viral breakthrough was defined as at least 1 documented hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL followed by HCV RNA level greater than or equal to 50 IU/mL during treatment.	Up to 24 weeks
Percentage of Participants With Missing Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) Data and/or Nonresponders Who Did Not Meet Specific SVR12 Nonresponder Criteria	The number of participants with missing SVR12 data or SVR12 nonresponder participants who did not meet criteria for on-treatment virologic failure, relapse, premature treatment discontinuation, and who did not have an Insufficient virological response reported was documented.	12 weeks after the last actual dose of study drug
Percentage of Participants With Virologic Response at End of Treatment (EoT)	Virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment.	Up to 24 weeks
Percentage of Participants With Relapse	Relapse was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment followed by HCV RNA level greater than or equal to 50 IU/mL.	Up to 48 weeks after the last actual dose of study drug
Percentage of Participants With On-treatment Virologic Failure	On-treatment virologic failure was defined as breakthrough (at least 1 documented hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL followed by HCV RNA greater than or equal to 50 IU/mL during treatment) or failure to suppress (each measured on-treatment HCV RNA value greater than or equal to 50 IU/mL).	12 weeks after the last actual dose of study drug
Percentage of Participants Meeting Relapse Criteria	Relapse was defined as hepatitis C virus ribonucleic acid (HCV RNA) less than 50 IU/mL at end of treatment or at the last on-treatment HCV RNA measurement followed by HCV RNA greater than or equal to 50 IU/mL post-treatment.	12 weeks after the last actual dose of study drug
Percentage of Participants Meeting Premature Study Drug Discontinuation Criteria	Premature study drug discontinuation was defined as participants who prematurely discontinued study drug with no on-treatment virologic failure.	12 weeks after the last actual dose of study drug
Percentage of Participants With Sufficient Follow-up Who Achieved Sustained Virological Response 12 Weeks Posttreatment	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 12 weeks after the last actual dose of study drug (CPSFU12) was defined as all participants who fulfilled one of the following criteria: evaluable HCV RNA data ≥70 days after the last actual dose of the ABBVIE REGIMEN; an HCV RNA value ≥50 IU/mL at the last measurement post-baseline; 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 AE) or virologic failure	12 weeks (at least 70 days) after the last actual dose of study drug

Collaborators and Investigators

• Sponsor: AbbVie

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 7, 2016
• Primary Completion (Actual): October 21, 2018
• Study Completion (Actual): October 21, 2018

Study Registration Dates

• First Submitted: June 14, 2016
• First Submitted That Met QC Criteria: June 14, 2016
• First Posted (Estimate): June 16, 2016

Study Record Updates

• Last Update Posted (Actual): October 11, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Observational Study; Chronic Hepatitis C; Chronic Hepatitis C genotype 1; Ombitasvir/paritaprevir/ritonavir ± dasabuvir; Chronic Hepatitis C genotype 4; Sustained Virological Response
• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ribavirin; Ritonavir
• Other Study ID Numbers: P16-014

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