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

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02851069

Acronym

outCome

Enrollment

Registered

2016-08-01

Start date

2017-02-23

Completion date

2018-08-30

Last updated

2019-09-18

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, Paritaprevir/r - Ombitasvir, ± Dasabuvir, Sustained Virological Response, Observational Study, Chronic Hepatitis C genotype 1

Brief summary

This is a prospective, multi-center observational study in adult participants chronically infected with hepatitis C virus (HCV) receiving the interferon-free ABBVIE REGIMEN (ombitasvir/paritaprevir/ritonavir with or without dasabuvir) with or without ribavirin (RBV). The prescription of a treatment regimen was at the discretion of the physician in accordance with local clinical practice and label. This study focused on collecting real world data. Follow-up visits, treatment, procedures and diagnostic methods followed physicians' routine clinical practice using a 12-week treatment regimen (four visits plus two interim data collection windows) or a 24-week treatment regimen (four visits plus three interim data collection windows) and is based on the anticipated regular follow-up for patients undergoing treatment for chronic hepatitis C (CHC). Participants are observed for the duration of the ABBVIE REGIMEN therapy and for up to 24 weeks after treatment completion.

Detailed description

This prospective, multi-center observational study in adult participants chronically infected with hepatitis C virus (HCV), receiving the interferon-free ABBVIE REGIMEN with or without RBV are offered the opportunity to participate in this study during a routine clinical visit at the participating sites at the discretion of the physician and is made independently from this observational study and preceded the decision to offer the participant the opportunity to participate in this study. After written informed consent is obtained, demographics, HCV disease characteristics, co-morbidities, co-medication, treatment details, and laboratory assessments as recorded in the participant's medical records (source documentation) are documented in the electronic case report form (eCRF). Participants are observed for the duration of the ABBVIE REGIMEN therapy and for up to 24 weeks after treatment completion. No patient identifiable information was captured; a unique participant number was automatically allocated by the web based system once the investigator or designee created a new participant file. This study focuses on collecting real world data. Follow-up visits, treatment, procedures and diagnostic methods follow physicians' routine clinical practice. The observational study period entailed the following data collection schemes: * 12-week treatment regimen: four visits plus two interim data collection windows * 24-week treatment regimen: four visits plus three interim data collection windows This schedule was based on the anticipated regular follow-up for patients undergoing treatment for CHC.

Interventions

None listed

Study design

Observational model

COHORT

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 CHC, genotype 1, receiving combination therapy with the interferon-free ABBVIE REGIMEN (ombitasvir/paritaprevir/ritonavir with or without dasabuvir) ± ribavirin (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). * Participant must not be participating or intending 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 at 12 Weeks (SVR12) Post-treatment	12 weeks (i.e. 70 to 126 days) after the last dose of study drug (up to 24 weeks)	SVR12 was defined as plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level ˂50 IU/mL 12 weeks after end of treatment (EoT) (defined as after last actual dose of the ABBVIE REGIMEN \[paritaprevir/ritonavir - ombitasvir ± dasabuvir\] or ribavirin \[RBV\]).

Secondary

Measure	Time frame	Description
Number of Participants Meeting Premature Study Drug Discontinuation	Up to EoT, maximum of 24 weeks	Premature study drug discontinuation was defined as participants who prematurely discontinued study drug (ABBVIE REGIMEN or RBV) and who experienced no on-treatment virologic failure (defined as breakthrough \[at least 1 documented HCV RNA ˂50 IU/mL followed by HCV RNA ≥50 IU/mL during treatment\] or failure to suppress \[each measured on-treatment HCV RNA value ≥50 IU/mL\]).
Percentage of Participants With Virologic Response at End of Treatment (EoT)	Up to EoT, maximum of 24 weeks	Virologic response is defined as HCV RNA level \<50 IU/mL.
Percentage of Participants Meeting Each and Any SVR12 Non-response Criteria	During treatment and 12 weeks (i.e. at least 70 days) after the last dose of study drug (up to 24 weeks)	For a participant to be include in this analysis, the participant needed to meet each and any of the following SVR12 non-response categories: * On-treatment virologic failure (breakthrough \[defined as at least one documented HCV RNA \<50 IU/mL followed by HCV RNA ≥50 IU/mL during treatment\] or failure to suppress \[each measured on-treatment HCV RNA value ≥50 IU/mL\]); * Relapse (defined as HCV RNA \<50 IU/mL at actual EoT followed by HCV RNA ≥50 IU/mL post-treatment for participants who completed treatment \[not more than 7 days shortened\]); * Premature study drug discontinuation with no on-treatment virologic failure; * Missing SVR12 data and/or none of the above criteria (including participants with missing SVR12 data). Abbreviations: EoT=end of treatment.
Percentage of Participants With Relapse	12 weeks (i.e. at least 70 days) after the last dose of study drug	Relapse was defined as confirmed HCV RNA \<50 IU/mL at EoT or at the last on-treatment HCV RNA measurement followed by HCV RNA ≥50 IU/mL post-treatment in participants who were treated.
Percentage of Participants With Relapse at EoT	12 weeks (i.e. at least 70 days) after the last dose of study drug	Relapse was defined as confirmed HCV RNA \<50 IU/mL at EoT followed by HCV RNA ≥50 IU/mL post treatment in participants who completed treatment (actual duration of ABBVIE REGIMEN is not shortened more than 7 days) and had HCV RNA results available in the SVR12 window.
Percentage of Participants With Viral Breakthrough	Up to EoT, maximum of 24 weeks	Viral breakthrough was defined as at least 1 documented HCV RNA \<50 IU/mL followed by HCV RNA ≥ 50 IU/mL during treatment.
Percentage of Participants Meeting On-treatment Virologic Failure	Up to EoT, maximum of 24 weeks	On-treatment virologic failure was defined as breakthrough (at least 1 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).
Percentage of Participants With Rapid Virologic Response at Week 4 (RVR4)	Week 4	RVR4 was defined as HCV RNA \< 50 IU/mL at Week 4.
Percentage of Participants With Sustained Virologic Response at 24 Weeks (SVR24) After EoT	24 weeks after EoT (up to 24 weeks)	SVR24 was defined as HCV RNA \< 50 IU/mL 24 weeks after EoT. During the course of the study, standard of care was changing and it was no longer common practice to assess SVR24.

Other

Measure	Time frame	Description
EQ-5D-5L Questionnaire Index Score: Change From Baseline to 24 Weeks Post EoT	24 weeks post EoT (up to 24 weeks)	The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by participants. The 5 items in the questionnaire 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 VAS. The higher the score, the worse the quality of life. For the VAS, the higher the score, the better the quality of life. Participant responses to the EQ-5D-5L were used to generate a HSI. HSI ranges is anchored at 0 (dead) and 1 (full health).
EQ-5D-5L Questionnaire VAS: Change From Baseline to EoT	End of Treatment (up to 24 weeks)	The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by participants. Participants also rated their perception of their overall health on a separate VAS. The scale is numbered from 0 to 100. The higher the score, the better the quality of life.
EQ-5D-5L Questionnaire VAS: Change From Baseline to 12 Weeks Post EoT	12 weeks post EoT (up to 24 weeks)	The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by participants. Participants also rated their perception of their overall health on a separate VAS. The scale is numbered from 0 to 100. The higher the score, the better the quality of life.
EQ-5D-5L Questionnaire VAS: Change From Baseline to 24 Weeks Post EoT	24 weeks post EoT (up to 24 weeks)	The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by participants. Participants also rated their perception of their overall health on a separate VAS. The scale is numbered from 0 to 100. The higher the score, the better the quality of life.
Number of Participants With Co-morbidities at Baseline (Day 0)	Baseline (Day 0)	Co-morbidities/co-infections were defined as hepatitis C virus (HCV) co-infections (human immunodeficiency virus \[HIV\] or hepatitis B virus \[HBV\], tuberculosis, schistosomiasis), liver/chronic hepatitis C (CHC) related co-morbidities (liver transplantation, hepatocellular carcinoma, non-alcoholic steatosis, alcoholic liver disease, primary biliary cirrhosis, auto-immune hepatitis, Wilson disease, cryoglobulinemia, porphyria cutanea tarda, auto-immune skin disease), and other co-morbidities (chronic kidney disease, psychiatric disorders, diabetes mellitus, insulin resistance, metabolic syndrome, lipid disorder, cardiovascular disease, immunologically mediated disease, hyper-/hypothyroidism, hemophilia, Thalassemia, sickle cell anemia, V. Willebrand disease, psychoactive substance dependency, kidney transplant, or other).
Number of Participants With Concomitant Medications	Day 0 to EoT, maximum 24 weeks	This includes all participants that took at least 1 concomitant medication from the time when the decision was made to initiate treatment with the ABBVIE REGIMEN until after the last dose. Abbreviations: ACE= angiotensin-converting-enzyme; GERD=gastroesophageal reflux.
EQ-5D-5L Questionnaire Index Score: Change From Baseline to 12 Weeks Post EoT	12 weeks post EoT (up to 24 weeks)	The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by participants. The 5 items in the questionnaire 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 VAS. The higher the score, the worse the quality of life. For the VAS, the higher the score, the better the quality of life. Participant responses to the EQ-5D-5L were used to generate a HSI. HSI ranges is anchored at 0 (dead) and 1 (full health).
EuroQol 5 Dimension 5 Level (EQ-5D-5L) Questionnaire Index Score: Change From Baseline to EoT	EoT (up to 24 weeks)	The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by participants. The 5 items in the questionnaire 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 VAS. The higher the score, the worse the quality of life. For the VAS, the higher the score, the better the quality of life. Participant responses to the EQ-5D-5L were used to generate a health status index (HSI). HSI ranges is anchored at 0 (dead) and 1 (full health).

Countries

Colombia

Participant flow

Pre-assignment details

A total of 66 participants were enrolled in the study; 1 participant never started treatment and thus the safety population was comprised of 65 participants. In this study, the safety population, target population, and core population were identical.

Participants by arm

Arm	Count
ABBVIE REGIMEN ± Ribavirin (RBV) ABBVIE REGIMEN (ombitasvir/paritaprevir/ritonavir with or without dasabuvir), and with or without weight-based ribavirin (± RBV) for 12 or 24 weeks	65
Total	65

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Failure to Return	3
Overall Study	Other	3

Baseline characteristics

Characteristic	ABBVIE REGIMEN ± Ribavirin (RBV)
Age, Continuous	61 years STANDARD_DEVIATION 11.2
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	65 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 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	62 Participants
Race (NIH/OMB) White	2 Participants
Sex: Female, Male Female	45 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 49	0 / 16
other Total, other adverse events	5 / 49	9 / 16
serious Total, serious adverse events	5 / 49	2 / 16

Outcome results

Primary

Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks (SVR12) Post-treatment

SVR12 was defined as plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level ˂50 IU/mL 12 weeks after end of treatment (EoT) (defined as after last actual dose of the ABBVIE REGIMEN \[paritaprevir/ritonavir - ombitasvir ± dasabuvir\] or ribavirin \[RBV\]).

Time frame: 12 weeks (i.e. 70 to 126 days) after the last dose of study drug (up to 24 weeks)

Population: Core Population (CP): defined as all participants of the target population (all participants in the safety population who met inclusion criteria) who were adequately treated according to the standard of care and within local label recommendations for their specific disease characteristics (cirrhotic status, genotype).

Arm	Measure	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants Achieving Sustained Virologic Response at 12 Weeks (SVR12) Post-treatment	87.7 percentage of participants

Secondary

Number of Participants Meeting Premature Study Drug Discontinuation

Premature study drug discontinuation was defined as participants who prematurely discontinued study drug (ABBVIE REGIMEN or RBV) and who experienced no on-treatment virologic failure (defined as breakthrough \[at least 1 documented HCV RNA ˂50 IU/mL followed by HCV RNA ≥50 IU/mL during treatment\] or failure to suppress \[each measured on-treatment HCV RNA value ≥50 IU/mL\]).

Time frame: Up to EoT, maximum of 24 weeks

Population: CP

Arm	Measure	Group	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Number of Participants Meeting Premature Study Drug Discontinuation	Premature Termination ABBVIE REGIMEN	4 participants
ABBVIE REGIMEN ± Ribavirin (RBV)	Number of Participants Meeting Premature Study Drug Discontinuation	No Premature Termination ABBVIE REGIMEN	61 participants

Secondary

Percentage of Participants Meeting Each and Any SVR12 Non-response Criteria

For a participant to be include in this analysis, the participant needed to meet each and any of the following SVR12 non-response categories: * On-treatment virologic failure (breakthrough \[defined as at least one documented HCV RNA \<50 IU/mL followed by HCV RNA ≥50 IU/mL during treatment\] or failure to suppress \[each measured on-treatment HCV RNA value ≥50 IU/mL\]); * Relapse (defined as HCV RNA \<50 IU/mL at actual EoT followed by HCV RNA ≥50 IU/mL post-treatment for participants who completed treatment \[not more than 7 days shortened\]); * Premature study drug discontinuation with no on-treatment virologic failure; * Missing SVR12 data and/or none of the above criteria (including participants with missing SVR12 data). Abbreviations: EoT=end of treatment.

Time frame: During treatment and 12 weeks (i.e. at least 70 days) after the last dose of study drug (up to 24 weeks)

Population: CP

Arm	Measure	Group	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants Meeting Each and Any SVR12 Non-response Criteria	Non-response 12 weeks after EoT	12.3 percentage of participants
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants Meeting Each and Any SVR12 Non-response Criteria	On-treatment virologic failure	1.5 percentage of participants
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants Meeting Each and Any SVR12 Non-response Criteria	Relapse	1.5 percentage of participants
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants Meeting Each and Any SVR12 Non-response Criteria	Premature treatment discontinuation	4.6 percentage of participants
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants Meeting Each and Any SVR12 Non-response Criteria	Missing SVR12 data/None of the above criteria	4.6 percentage of participants

Secondary

Percentage of Participants Meeting On-treatment Virologic Failure

On-treatment virologic failure was defined as breakthrough (at least 1 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).

Time frame: Up to EoT, maximum of 24 weeks

Population: CP

Arm	Measure	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants Meeting On-treatment Virologic Failure	1.5 percentage of participants

Secondary

Percentage of Participants With Rapid Virologic Response at Week 4 (RVR4)

RVR4 was defined as HCV RNA \< 50 IU/mL at Week 4.

Time frame: Week 4

Population: CP

Arm	Measure	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants With Rapid Virologic Response at Week 4 (RVR4)	66.2 percentage of participants

Secondary

Percentage of Participants With Relapse

Relapse was defined as confirmed HCV RNA \<50 IU/mL at EoT or at the last on-treatment HCV RNA measurement followed by HCV RNA ≥50 IU/mL post-treatment in participants who were treated.

Time frame: 12 weeks (i.e. at least 70 days) after the last dose of study drug

Population: CP

Arm	Measure	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants With Relapse	1.5 percentage of participants

Secondary

Percentage of Participants With Relapse at EoT

Relapse was defined as confirmed HCV RNA \<50 IU/mL at EoT followed by HCV RNA ≥50 IU/mL post treatment in participants who completed treatment (actual duration of ABBVIE REGIMEN is not shortened more than 7 days) and had HCV RNA results available in the SVR12 window.

Time frame: 12 weeks (i.e. at least 70 days) after the last dose of study drug

Population: CP of participants with EoT response whose last post-treatment HCV RNA test result did not show virologic response

Arm	Measure	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants With Relapse at EoT	1.8 percentage of participants

Secondary

Percentage of Participants With Sustained Virologic Response at 24 Weeks (SVR24) After EoT

SVR24 was defined as HCV RNA \< 50 IU/mL 24 weeks after EoT. During the course of the study, standard of care was changing and it was no longer common practice to assess SVR24.

Time frame: 24 weeks after EoT (up to 24 weeks)

Population: CP participants with an SVR24 assessment

Arm	Measure	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants With Sustained Virologic Response at 24 Weeks (SVR24) After EoT	44.4 percentage of participants

Secondary

Percentage of Participants With Viral Breakthrough

Viral breakthrough was defined as at least 1 documented HCV RNA \<50 IU/mL followed by HCV RNA ≥ 50 IU/mL during treatment.

Time frame: Up to EoT, maximum of 24 weeks

Population: CP

Arm	Measure	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants With Viral Breakthrough	0.0 percentage of participants

Secondary

Percentage of Participants With Virologic Response at End of Treatment (EoT)

Virologic response is defined as HCV RNA level \<50 IU/mL.

Time frame: Up to EoT, maximum of 24 weeks

Population: CP

Arm	Measure	Value (NUMBER)
ABBVIE REGIMEN ± Ribavirin (RBV)	Percentage of Participants With Virologic Response at End of Treatment (EoT)	95.4 percentage of participants

Other Pre-specified

EQ-5D-5L Questionnaire Index Score: Change From Baseline to 12 Weeks Post EoT

The EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by participants. The 5 items in the questionnaire 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 VAS. The higher the score, the worse the quality of life. For the VAS, the higher the score, the better the quality of life. Participant responses to the EQ-5D-5L were used to generate a HSI. HSI ranges is anchored at 0 (dead) and 1 (full health).

Time frame: 12 weeks post EoT (up to 24 weeks)