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

Study Overview
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Brief Summary
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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
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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]).

Official Title
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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)

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Ombitasvir/paritaprevir/ritonavir
* Drug: Dasabuvir
* Drug: Ribavirin
* Behavioral: Patient support program


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with HCV genotype 1 or 4<br>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<br>* Co-formulated tablet<br>* Other names: Paritaprevir also known as ABT-450;Drug: Dasabuvir<br>* Tablet<br>* Other names: ABT-333;Drug: Ribavirin<br>* Tablet<br>Behavioral: Patient support program<br>* Supportive services provided to participants included reminder calls, emails, text messages, a Care Coach, and educational/informational materials.<br>|

What is the study measuring?
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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 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 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 | 
| 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 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 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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C, Ombitasvir/paritaprevir/ritonavir ± dasabuvir, Sustained Virological Response, Observational Study, Chronic Hepatitis C genotype 1, Chronic Hepatitis C genotype 4