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

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)

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02803138

Acronym

CITRINE

Enrollment

256

Registered

2016-06-16

Start date

2016-07-07

Completion date

2018-10-21

Last updated

2019-10-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis C

Keywords

Chronic Hepatitis C, Ombitasvir/paritaprevir/ritonavir ± dasabuvir, Sustained Virological Response, Observational Study, Chronic Hepatitis C genotype 1, Chronic Hepatitis C genotype 4

Brief summary

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.

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 \[SVR24\]).

Interventions

DRUGOmbitasvir/paritaprevir/ritonavir

Co-formulated tablet

DRUGDasabuvir

Tablet

DRUGRibavirin

Tablet

BEHAVIORALPatient support program

Supportive services provided to participants included reminder calls, emails, text messages, a Care Coach, and educational/informational materials.

Study design

Observational model

CASE_ONLY

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* 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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-treatment (SVR12)	12 weeks after the last actual dose of study drug	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.

Secondary

Measure	Time frame	Description
Percentage of Participants With Sufficient Follow-up Who Achieved Sustained Virological Response 12 Weeks Posttreatment	12 weeks (at least 70 days) after the last actual dose of study drug	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
Percentage of Participants With Relapse	Up to 48 weeks after the last actual dose of study drug	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.
Percentage of Participants With Viral Breakthrough	Up to 24 weeks	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.
Percentage of Participants With Virologic Response at End of Treatment (EoT)	Up to 24 weeks	Virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than 50 IU/mL at the end of treatment.
Percentage of Participants Meeting Relapse Criteria	12 weeks after the last actual dose of study drug	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.
Percentage of Participants Meeting Premature Study Drug Discontinuation Criteria	12 weeks after the last actual dose of study drug	Premature study drug discontinuation was defined as participants who prematurely discontinued study drug with no on-treatment virologic failure.
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	12 weeks after the last actual dose of study drug	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.
Percentage of Participants With On-treatment Virologic Failure	12 weeks after the last actual dose of study drug	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).

Countries

Israel

Participant flow

Pre-assignment details

Safety population: all enrolled participants who received at least 1 dose of the ABBVIE REGIMEN. The prescribed ABBVIE REGIMEN needed to be known. 256 participants enrolled; treatment was not started in 20 participants. The death noted below occurred during the SAE collection period.

Participants by arm

Arm	Count
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	236
Total	236

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	1
Overall Study	Failure to return	38
Overall Study	Insufficient virological response	2
Overall Study	Other, not specified	28
Overall Study	Withdrawn consent	1

Baseline characteristics

Characteristic	Participants With HCV Genotype 1 or 4
Age, Continuous	56 years STANDARD_DEVIATION 12.7
Hepatitis C genotype Genotype 1a	12 Participants
Hepatitis C genotype Genotype 1a/1b	1 Participants
Hepatitis C genotype Genotype 1b	222 Participants
Hepatitis C genotype Genotype 4	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	236 Participants
Sex: Female, Male Female	105 Participants
Sex: Female, Male Male	131 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	1 / 216	0 / 6	0 / 14
other Total, other adverse events	15 / 216	2 / 6	4 / 14
serious Total, serious adverse events	4 / 216	1 / 6	1 / 14

Outcome results

Primary

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.