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Trial record 65 of 115 for:    "Viral Infectious Disease" | "Ledipasvir"

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

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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

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.


Condition or disease Intervention/treatment
Chronic Hepatitis C Infection Drug: Telaprevir Drug: Boceprevir Drug: Sofosbuvir Drug: Simeprevir Drug: Daclatasvir Drug: Ledipasvir Drug: ritonavir-boosted Paritaprevir/ Ombitasvir Drug: Dasabuvir Drug: Velpatasvir Drug: Elbasvir Drug: Grazoprevir

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.


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Study Type : Observational
Estimated Enrollment : 1000 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Efficacy and Safety of Treatment Against Hepatitis C Virus Infection Based on Direct-acting Antivirals in Real-life Conditions: The GEHEP Cohort
Study Start Date : December 2014
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
IFN
HCV-infected patients, pre-treated or treatment-naïve, who start a regimen containing pegylated interferon in combination with any DAA
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

IFN-free
HCV-infected patients, pre-treated or treatment-naïve, who start a regimen containing one or more DAA
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




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Identification of predictors of SVR [ Time Frame: 48 weeks ]
  2. Analyze efficacy and safety in patients that receive methadone maintenance therapy [ Time Frame: 48 weeks ]
  3. Analyze efficacy and safety according to previous treatment outcome [ Time Frame: 48 weeks ]
  4. Analyze efficacy and safety in patients with cirrhosis [ Time Frame: 48 weeks ]
  5. Evaluate impact of SVR on biological, elastographical and clinical parameters [ Time Frame: 48 hours ]

Biospecimen Retention:   Samples With DNA
whole blood samples


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
HCV-infected patients who initiated treatment against HCV including a direct-acting antiviral
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02333292


Contacts
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Contact: Karin I Neukam, Dr 0034955015871 karin.neukam@gmail.com
Contact: Juan A Pineda, Dr 0034955015684 japineda@telefonica.net

Locations
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Spain
Valme University Hospital Recruiting
Seville, Andalusia, Spain, 41014
Contact: Karin I Neukam, Dr    0034955015871    karin.neukam@gmail.com   
Contact: Juan A Pineda, Dr    0034955015684    japineda@telefonica.net   
Sponsors and Collaborators
Valme University Hospital
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
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Principal Investigator: Karin I Neukam, Dr Valme University Hospital

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Responsible Party: Karin Neukam, Dr, Valme University Hospital
ClinicalTrials.gov Identifier: NCT02333292     History of Changes
Other Study ID Numbers: GEHEP-MONO
GEHEP-001 ( Other Identifier: SEIMC-GEHEP )
First Posted: January 7, 2015    Key Record Dates
Last Update Posted: October 17, 2016
Last Verified: October 2016
Additional relevant MeSH terms:
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Virus Diseases
RNA Virus Infections
Ledipasvir
Infection
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
Hepatitis, Chronic
Ritonavir
Sofosbuvir
MK-5172
Simeprevir
Velpatasvir
Antiviral Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors