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Efficacy and Safety of Therapy Against HCV Based on Direct-acting Antivirals in Real-life Conditions (FPSMON201401)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02333292
Recruitment Status : Recruiting
First Posted : January 7, 2015
Last Update Posted : October 17, 2016
Sponsor:
Collaborators:
Hospital del SAS de Jerez
Hospital General Universitario Elche
Hospital La Línea de la Concepción
Complexo Hospitalario Universitario de A Coruña
Hospital de Figueres
Hospital Universitario Puerto Real
Hospital Universitario Virgen de la Victoria
Hospital Universitario de Canarias
Hospital General Universitario de Alicante
Hospital Universitario Araba
Hospital Royo Vilanova
Hospital Universitario de Burgos
Complejo Hospitalario Universitario de Huelva
Hospital Universitario Reina Sofia de Cordoba
Hospital Universitario Virgen Macarena
Complexo Hospitalario Universitario de Vigo
Clinica Universidad de Navarra, Universidad de Navarra
Hospital Clinico Universitario San Cecilio
Hospital Universitario La Fe
Hospital General Universitario de Valencia
Hospital Universitario Infanta Leonor
Hospital Universitario de Gran Canaria
Hospital General Universitario Santa Lucía
Centro Penitenciario Alicante 1
Hospital Regional Universitario Carlos Haya
Hospital Virgen de la Luz
Hospital General Universitario de Castellón
Hospital Parc Taulí, Sabadell
Information provided by (Responsible Party):
Karin Neukam, Valme University Hospital

Tracking Information
First Submitted Date December 15, 2014
First Posted Date January 7, 2015
Last Update Posted Date October 17, 2016
Study Start Date December 2014
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: January 5, 2015)
  • Proportion of Patients with Sustained Virological Response [ Time Frame: 48 weeks ]
    Efficacy of treatment against hepatitis C virus infection based on direct-acting antivirals in real-life conditions as reflected in proportion of patients who achieve sustained virological response 12 weeks after end of therapy.
  • Number of Participants with Adverse Events [ Time Frame: 48 weeks ]
    Safety of treatment against hepatitis C virus infection based on direct-acting antivirals in real-life conditions as reflected in the number of patients with adverse events.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: January 5, 2015)
  • Identification of predictors of SVR [ Time Frame: 48 weeks ]
  • Analyze efficacy and safety in patients that receive methadone maintenance therapy [ Time Frame: 48 weeks ]
  • Analyze efficacy and safety according to previous treatment outcome [ Time Frame: 48 weeks ]
  • Analyze efficacy and safety in patients with cirrhosis [ Time Frame: 48 weeks ]
  • Evaluate impact of SVR on biological, elastographical and clinical parameters [ Time Frame: 48 hours ]
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Efficacy and Safety of Therapy Against HCV Based on Direct-acting Antivirals in Real-life Conditions
Official Title Efficacy and Safety of Treatment Against Hepatitis C Virus Infection Based on Direct-acting Antivirals in Real-life Conditions: The GEHEP Cohort
Brief Summary

Objectives: 1) To evaluate la proportion of hepatitic C virus (HCV)-monoinfected patients who show sustained virologic response (SVR) to treatment including direct-acting antivirals (DAAs) in the clinical practice in clinical units that treat infectious diseases and 2) to determine the frequency of adverse events, including those that are severe and/or cause treatment interruption, in DAA-based therapy in this setting.

Design: Multicentric, prospective post-authorised cohort study. Setting: Hospitals of the Hepatitis Study Group (GEHEP) of the Spanish Society of Infectious Diseases and Microbiology (SEIMC).

Study population: HCV-monoinfected patients that initiate DAA-based treatment outside clinical trials.

Variables: The primary efficacy outcome variable is the proportion of patients who reach undetectable HCV-RNA 12 weeks after the scheduled end of therapy (SVR12). The primary safety outcome variable is the percentage of subjects who discontinue therapy due to adverse events.

Statistical analysis: A descriptive study will be performed, as well as a double sensibility analysis of the frequency of SVR12 using both an intention-to-treat and an on-treatment approach. Those variables that are associated with SVR12 with a p-value <0.2 will be included in a logistic regression analysis in which SVR12 will be the dependent variable.

Detailed Description

The incidence of hepatic decompensations and mortality is reduced considerable in patients who achieve sustained virologic response (SVR) to therapy against hepatitis C virus (HCV) infection. With the arrival of direct-acting antivirals (AAD) against HCV, rates of SVR are significantly higher than what was achieved with pegylated interferon (peg-IFN) in combination with ribavirin (RBV). Therefore, AADs could have a high impact in this context. Therefore, triple therapy against HCV genotype 1 based on the first-generation protease inhibitors (PI) telaprevir (TVR) or boceprevir (BOC) plus peg-IFN/RBV became standard therapy in 2011 and SVR rates as high as 68%-75% were reached in treatment-naïve patients. In treatment-experienced subjects, retreatment with triple therapy resulted in higher SVR rates than what was observed with dual therapy alone, however, treatment success strongly depends on the previous response pattern. Unfortunately, combinations based on TVR or BOC are not well tolerated, treatments are complex, costs are high and pharmacological interactions are frequently observed.

The next generation of DAAs offers increased response rates and, furthermore, a better safety pattern than TVR or BOC. Additionally, the dosing of the newer DAAs is easier and more convenient, and pharmacological interactions of the newer DAAs are easier to manage or even not relevant. The FDA has approved the second-generation PI simeprevir, the HCV non-structural (NS) protein NS 5B inhibitor sofosbuvir, as well as the inhibitors of NS 5A daclatasvir and ledipasvir. Apart from a better efficacy, safety and convenience, these new DAAs are active against HCV genotypes other than 1. Finally, some of the new DAAs can be administered in interferon-free regimens and therefore offer treatment options for interferon-intolerant individuals or for those with a contraindication for peg-IFN. Therefore, in the near future, the vast majority of HCV monoinfected patients will be treated with a combination including a DAA. Currently, the main problem is the high cost of the DAAs challenging the health systems.

In spite of the positive prospect regarding response rates to DAAs, there are a number of questions to be answered as soon as possible. On the one hand, the information on efficacy and safety of the DAAs available to date is derived from clinical trials that do not reflect the circumstances of the clinical practice. In this context, clinical trials usually include a considerably low proportion of patients with certain characteristics, such as cirrhotics. Data from the French cohort CUPIC reveal that this subgroup shows a lower tolerability of TVR or BOC than that reported in pivotal clinical trials. In fact, data obtained from this cohort resulted in a change of treatment guidelines for HCV monoinfected patients published by the Spanish Agency of Medicines. On the contrary, there is evidence based on observations made within the expanded access program study HEP3002 that individuals with advanced fibrosis show a efficacy and safety profile when treated with triple therapy that is more similar to that observed in clinical trials than within the CUPIC cohort. Nevertheless, in this study, exclusion criteria and follow-up were comparable to what is applied in clinical trials. Therefore, the study population may not reflect exactly the patient profile seen in real-life.

Currently, information on the distinct aspects of treatment against HCV including DAAs under real-life conditions in Spain is scarce. Clinicians at the Infectious Diseases Units treat a high number of HCV monoinfected patients. These physicians are confronted with a patient population in which a history of drug abuse is predominant, the majority of the individuals having consumed injecting drugs, who frequently suffer psychiatric pathology and who receive concomitant therapy that cause problems regarding drug-drug interactions and adherence. Also, the HCV genotype distribution is different to what is observed in Hepatology Units, being the genotype 1a predominant as compared to 1b, 3 and 4. Taken into account what was mentioned above, these factors could cause different rates of SVR to DAAs, interruptions and voluntary drop-outs as compared to what has been reported, especially in the difficult-to-treat population.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
whole blood samples
Sampling Method Probability Sample
Study Population HCV-infected patients who initiated treatment against HCV including a direct-acting antiviral
Condition Chronic Hepatitis C Infection
Intervention
  • Drug: Telaprevir
    Initiation of a regimen containing TVR
    Other Name: TVR
  • Drug: Boceprevir
    Initiation of a regimen containing BOC
    Other Name: BOC
  • Drug: Sofosbuvir
    Initiation of a regimen containing SOF
    Other Name: SOF
  • Drug: Simeprevir
    Initiation of a regimen containing SMV
    Other Name: SMV
  • Drug: Daclatasvir
    Initiation of a regimen containing DCV
    Other Name: DCV
  • Drug: Ledipasvir
    Initiation of a regimen containing LDV
    Other Name: LDV
  • Drug: ritonavir-boosted Paritaprevir/ Ombitasvir
    Initiation of a drug combination of PTV/OTV
    Other Name: PTV/OTV
  • Drug: Dasabuvir
    Initiation of a regimen containing DBV
    Other Name: DBV
  • Drug: Velpatasvir
    Initiation of a regimen containing VPV
    Other Name: VPV
  • Drug: Elbasvir
    Initiation of a regimen containing EBV
    Other Name: EBV
  • Drug: Grazoprevir
    Initiation of a regimen containing GZR
    Other Name: GZR
Study Groups/Cohorts
  • IFN
    HCV-infected patients, pre-treated or treatment-naïve, who start a regimen containing pegylated interferon in combination with any DAA
    Interventions:
    • Drug: Telaprevir
    • Drug: Boceprevir
    • Drug: Sofosbuvir
    • Drug: Simeprevir
  • IFN-free
    HCV-infected patients, pre-treated or treatment-naïve, who start a regimen containing one or more DAA
    Interventions:
    • Drug: Sofosbuvir
    • Drug: Simeprevir
    • Drug: Daclatasvir
    • Drug: Ledipasvir
    • Drug: ritonavir-boosted Paritaprevir/ Ombitasvir
    • Drug: Dasabuvir
    • Drug: Velpatasvir
    • Drug: Elbasvir
    • Drug: Grazoprevir
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: November 10, 2015)
1000
Original Estimated Enrollment
 (submitted: January 5, 2015)
210
Estimated Study Completion Date December 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • older than 18 years
  • initiation of therapy including a direct-acting antiviral against HCV

Exclusion Criteria:

  • HIV-infection
  • unable to provide written informed consent
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Karin I Neukam, Dr 0034955015871 karin.neukam@gmail.com
Contact: Juan A Pineda, Dr 0034955015684 japineda@telefonica.net
Listed Location Countries Spain
Removed Location Countries  
 
Administrative Information
NCT Number NCT02333292
Other Study ID Numbers GEHEP-MONO
GEHEP-001 ( Other Identifier: SEIMC-GEHEP )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Karin Neukam, Valme University Hospital
Study Sponsor Valme University Hospital
Collaborators
  • Hospital del SAS de Jerez
  • Hospital General Universitario Elche
  • Hospital La Línea de la Concepción
  • Complexo Hospitalario Universitario de A Coruña
  • Hospital de Figueres
  • Hospital Universitario Puerto Real
  • Hospital Universitario Virgen de la Victoria
  • Hospital Universitario de Canarias
  • Hospital General Universitario de Alicante
  • Hospital Universitario Araba
  • Hospital Royo Vilanova
  • Hospital Universitario de Burgos
  • Complejo Hospitalario Universitario de Huelva
  • Hospital Universitario Reina Sofia de Cordoba
  • Hospital Universitario Virgen Macarena
  • Complexo Hospitalario Universitario de Vigo
  • Clinica Universidad de Navarra, Universidad de Navarra
  • Hospital Clinico Universitario San Cecilio
  • Hospital Universitario La Fe
  • Hospital General Universitario de Valencia
  • Hospital Universitario Infanta Leonor
  • Hospital Universitario de Gran Canaria
  • Hospital General Universitario Santa Lucía
  • Centro Penitenciario Alicante 1
  • Hospital Regional Universitario Carlos Haya
  • Hospital Virgen de la Luz
  • Hospital General Universitario de Castellón
  • Hospital Parc Taulí, Sabadell
Investigators
Principal Investigator: Karin I Neukam, Dr Valme University Hospital
PRS Account Valme University Hospital
Verification Date October 2016