The Effectiveness of Paritaprevir/Ritonavir - Ombitasvir, ± Dasabuvir, ± Ribavirin in France

Chronic Hepatitis C Clinical Trial

— OPALE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02618928
• Other study ID #: P15-405
• Status: Completed
• Start date: December 15, 2015
• Est. completion date: March 29, 2018

Study information

• Verified date: February 2019
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study seeks to determine the effectiveness of the interferon-free ABBVIE REGIMEN ± ribavirin (RBV) in participants with chronic hepatitis C (CHC) virus in clinical practices across France.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 735
• Est. completion date: March 29, 2018
• Est. primary completion date: March 29, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Treatment-naïve or -experienced participants with confirmed CHC, genotype 1 or 4

• Participants receiving or who will receive the interferon-free ABBVIE REGIMEN ± RBV according to product label

• RBV prescribed in line with the current local label

Exclusion Criteria:

• Participant is not participating or intending to participate in a concurrent interventional therapeutic trial

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Locations

Country	Name	City	State
France	C.H. du Pays d'Aix /ID# 144922	Aix En Provence
France	Cabinet medical /ID# 147359	Aix En Provence
France	CHU Amiens Picardie /ID# 145871	Amiens CEDEX 1	Somme
France	CHU d'Angers /ID# 145880	Angers
France	Centre Hospitalier Victor Dupo /ID# 147241	Argenteuil
France	Centre Hospitalier D'Avignon /ID# 151098	Avignon
France	Centre Hospitalier D'Avignon /ID# 151343	Avignon
France	Cabinet Medical /ID# 147322	Besancon
France	CHU de Besancon - Jean Minjoz /ID# 145884	Besancon	Doubs
France	Centre Endo Nord Isere /ID# 148694	Bourgoin Jallieu
France	Centre Hospitalier Universitai /ID# 147568	Caen
France	CH de Chambery /ID# 145573	Chambery
France	Hopital Antoine Beclere /ID# 149251	Clamart
France	Hopital Antoine Beclere /ID# 149252	Clamart
France	Hopital Beaujon /ID# 147923	Clichy	Ile-de-France
France	Centre Hosp Intercommunal /ID# 145876	Creteil
France	Hospital Henri Mondor /ID# 144918	Creteil
France	Clinique du Palais /ID# 145563	Grasse
France	CHU de Grenoble - Albet Michal /ID# 145881	Grenoble
France	CH d'Hyeres /ID# 145870	Hyeres
France	Ch Du Mans /Id# 147415	Le Mans
France	Dr. Cuissard, Le Port, FR /ID# 145565	Le Port
France	Centre Hospitalier de Libourne /ID# 145564	Libourne
France	CHU Dupuytren /ID# 144920	Limoges CEDEX 1	Franche-Comte
France	CH Des Deux Vallees Longumeau /ID# 149336	Longjumeau
France	Ctr Consultations La Sauvegard /ID# 147236	Lyon
France	Hopital de la Croix Rousse /ID# 149776	Lyon
France	Hopital de la Timone /ID# 147237	Marseille
France	Hopital de la Timone /ID# 145558	Marseille CEDEX 05	Provence-Alpes-Cote-d Azur
France	Hopital de la Timone /ID# 145574	Marseille CEDEX 05	Provence-Alpes-Cote-d Azur
France	Hopital Saint Joseph /ID# 144927	Marseille CEDEX 08	Bouches-du-Rhone
France	Hopital Saint Joseph /ID# 145560	Marseille CEDEX 08	Bouches-du-Rhone
France	Hopital Saint Joseph /ID# 145571	Marseille CEDEX 08	Bouches-du-Rhone
France	Ctre Hosp de Montelimar /ID# 147239	Montelimar
France	Hopital Saint Eloi /ID# 144919	Montpellier CEDEX 5	Herault
France	Cabinet Medical, Boyer Darrigr /ID# 145562	Nanterre
France	CHU de Nice /ID# 144921	Nice
France	Cabinet Medical, Dr. Verdier, /ID# 145575	Nimes
France	CHR Orleans - Hopital de la Source /ID# 147250	Orleans CEDEX 2	Centre-Val De Loire
France	Cabinet Medical /ID# 145559	Paris
France	Cabinet Medical, Giuily /ID# 145882	Paris
France	Hopital Bichat Claude Bernard /ID# 145886	Paris
France	Hopital Bichat-Claude Bernard /ID# 149246	Paris
France	Hopital Pitie Salpetriere /ID# 145556	Paris
France	Hopital Pitie Salpetriere /ID# 145566	Paris
France	Hopital Pitie Salpetriere /ID# 149337	Paris
France	Hopital Saint Antoine /ID# 145567	Paris
France	Hopital Saint Antoine /ID# 148635	Paris
France	Hopital Saint Antoine /ID# 148693	Paris
France	Hopital Saint Antoine /ID# 152825	Paris
France	Hopital Tenon /ID# 145885	Paris
France	CH Marechal Joffre /ID# 145875	Perpignan
France	CHU Jean Bernard /ID# 147414	Poitiers
France	CHU de Reims /ID# 148477	Reims
France	Hospital Pontchaillou /ID# 145883	Rennes
France	Charles Nicolle Hosp chu rouen /ID# 145557	Rouen
France	Institut Arnault Tzanck /ID# 144925	Saint Laurent Du Var
France	Hopital Begin /ID# 145872	Saint Mande
France	CHU Strasbourg Hautepierre Hos /ID# 147246	Strasbourg
France	Hopital Foch /ID# 147248	Suresnes
France	Cabinet Medical, Dr. Constant, /ID# 145561	Toulon
France	Clinique Amroise Pare /ID# 144924	Toulouse
France	Hopital Joseph Ducuing /ID# 152832	Toulouse
France	Hopital Universitaire Purpan /ID# 145869	Toulouse	Haute-Garonne
France	Hopital Universitaire Purpan /ID# 150141	Toulouse	Haute-Garonne
France	Ctre Hospitalier de Tourcoing /ID# 145568	Tourcoing
France	Cabinet Medical, Barbereau /ID# 145874	Tours
France	Hopital Paul Brousse /ID# 145879	Villejuif
France	Hopital Paul Brousse /ID# 147244	Villejuif
France	Hopital Paul Brousse /ID# 147417	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 20, 24, or 36 depending on the treatment regimen)
Secondary	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 8, 12, or 24 depending on the treatment regimen)
Secondary	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 20, 24, or 36 depending on the treatment regimen)
Secondary	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 8, 12, or 24 depending on the treatment regimen) and up to 24 weeks after the end of treatment.
Secondary	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.	8, 12, or 24 weeks (depending on the treatment regimen)
Secondary	Percentage of Participants With Rapid Virological Response at Week 4 (RVR4)	RVR 4 was defined as participants with HCV RNA < 50 IU/mL at week 4.	Week 4
Secondary	Percentage of Participants With Sufficient Follow-up Who Achieved Sustained Virological Response 24 Weeks Post-treatment (SVR24)	Sustained virologic response was defined as hepatitis C virus ribonucleic acid (HCV RNA) levels less than 50 IU/mL 24 weeks after the last dose of study drug.; The Core population with sufficient follow-up data regarding SVR24 included all core population participants who; had evaluable HCV RNA data = 126 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 = 126 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.	24 weeks after the last dose of study drug (week 32, 36, or 48 depending on the treatment regimen)
Secondary	Number 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); Death; Premature treatment discontinuation with no on-treatment virologic failure; Insufficient virological response reported or HCV RNA = 50 IU/mL post-EOT and none of the above criteria; Missing SVR12 data and/or none of the above criteria.	12 weeks after the last dose of study drug (week 20, 24, or 36 depending on the treatment regimen)
Secondary	Percentage of Participants With Adherence to the ABBVIE Regimen, by Adherence Category	Adherence to the ABBVIE treatment regimen is expressed as a percentage of the target dose and was calculated as: Cumulative dose taken / (initial prescribed dose * planned duration) * 100 The ABBVIE regimen consists of paritaprevir/r and ombitasvir with or without dasabuvir.	From first dose of study drug to end of treatment, 8 to 24 weeks depending on the treatment regimen.
Secondary	Percentage of Participants With Adherence to Ribavirin by Adherence Category	Adherence to ribavirin is expressed as a percentage of the target dose, and was calculated as: Cumulative dose taken / (initial prescribed dose * planned duration) * 100	From first dose of study drug to end of treatment, 8 to 24 weeks depending on the treatment regimen.
Secondary	Percentage of Ribavirin Treatment Days in Relation to the Target Number of Ribavirin Treatment Days		From first dose of study drug to end of treatment, 8 to 24 weeks depending on the treatment regimen.
Secondary	Number of Participants Who Received Concomitant Medications	Concomitant medication other than for chronic hepatitis C used from the time when the decision was made to initiate treatment with paritaprevir/ritonavir and ombitasvir with or without dasabuvir until after the last dose.	From first dose of study drug to end of treatment, 8 to 24 weeks depending on the treatment regimen
Secondary	Number of Participants With Adverse Events, Serious Adverse Events, or Pregnancies		From first dose of study drug through 30 days after last dose (12 to 28 weeks depending on treatment regimen). The median (minimum, maximum) duration of treatment was 84 (4, 167) days.
Secondary	Change From Baseline in Fatigue Impact Scale Total Score	The Fatigue Impact Scale (FIS) questionnaire was used to assess the impact of fatigue on the quality of life of patients.; The FIS consists of 40 items, each of which is scored 0 (no problem) to 4 (extreme problem), providing a total score from of 0 to 160, where a lower score = less fatigue impact	Baseline, end of treatment (week 8, 12, or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment
Secondary	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 8, 12, or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment
Secondary	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 8, 12, or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment
Secondary	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 8, 12, or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment
Secondary	Change From Baseline in Work Productivity and Activity Impairment (WPAI): Presenteeism	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.; Presenteeism indicates the percentage of impairment while working due to health problems.	Baseline, end of treatment (week 8, 12, or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment
Secondary	Change From Baseline in Work Productivity and Activity Impairment (WPAI): Total Work Productivity Impairment (TWP)	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.; Total work productivity impairment (TWP) indicates the percentage of overall work impairment due to health problems.	Baseline, end of treatment (week 8, 12, or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment
Secondary	Change From Baseline in Work Productivity and Activity Impairment (WPAI): Total Activity Impairment	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.; Total activity impairment (TAI) indicates the percentage of general (non-work) activity impairment due to health problems.	Baseline, end of treatment (week 8, 12, or 24 depending on the treatment regimen), and at 12 and 24 weeks after end of treatment
Secondary	Change From Baseline in Beliefs Medication Questionnaire - (18-item BMQ)	The BMQ consists of 2 sections and 18 questions to screen for patients' beliefs, attitudes and concerns about their medication. The BMQ-Specific section comprises two 5-item subscales assessing the necessity of and concerns about the prescribed medication (Specific-Necessity and Specific-Concerns). The BMQ-General section comprises two 4-item subscales assessing beliefs that medicines are harmful and overused by doctors in general (General-Harm and General-Overuse). The 18 items are rated on a Likert scale from 1 (strongly disagree) to 5 (strongly agree). Each subscale score ranges from 1 to 5. High scores in the Specific-Concerns scale represent the notion that adverse reactions are potentially harmful when taking medication on a regular basis, and high scores in the Specific-Necessity scale indicate the patient's need to adhere to medication to maintain health. High scores in the General-Harm and General-Overuse scales represent an overall negative perception of medication.	Baseline and end of treatment (week 8, 12, or 24 depending on the treatment regimen)
Secondary	Change From Baseline in Patient Activation Measure 13 (PAM-13)	PAM 13 is a measure used to assess the patient knowledge, skill, and confidence for self-management, consisting of 13 questions. Each of the 13 items can be answered with one of four possible response options, which are "disagree strongly" (1), "disagree" (2), "agree" (3), "agree strongly" (4). Scores were summed to calculate the overall raw score, then transformed to a scale with a theoretical range 0 to 100, based on calibration tables, with higher PAM scores indicating higher patient activation.	Baseline and end of treatment (week 8, 12, or 24 depending on the treatment regimen)
Secondary	Number of Participants With Outpatient Consultations Due to Liver Disease by Category		From first dose of study drug through 30 days after last dose (12 to 28 weeks depending on treatment regimen). The median (minimum, maximum) duration of treatment was 84 (4, 167) days.
Secondary	Number of Participants With Hospitalizations Due to Liver Disease by Category		From first dose of study drug through 30 days after last dose (12 to 28 weeks depending on treatment regimen). The median (minimum, maximum) duration of treatment was 84 (4, 167) days.
Secondary	Change From Baseline in Percent Glycosylated Hemoglobin (HbA1c)		Baseline and end of treatment (week 8, 12, or 24 depending on the treatment regimen)

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