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

NCT ID: NCT02333292

Last Updated: 2022-06-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

1128 participants

Study Classification

OBSERVATIONAL

Study Start Date

2014-12-31

Study Completion Date

2017-06-30

Brief Summary

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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

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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.

Conditions

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Chronic Hepatitis C Infection

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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IFN

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

Telaprevir

Intervention Type DRUG

Initiation of a regimen containing TVR

Boceprevir

Intervention Type DRUG

Initiation of a regimen containing BOC

Sofosbuvir

Intervention Type DRUG

Initiation of a regimen containing SOF

Simeprevir

Intervention Type DRUG

Initiation of a regimen containing SMV

IFN-free

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

Sofosbuvir

Intervention Type DRUG

Initiation of a regimen containing SOF

Simeprevir

Intervention Type DRUG

Initiation of a regimen containing SMV

Daclatasvir

Intervention Type DRUG

Initiation of a regimen containing DCV

Ledipasvir

Intervention Type DRUG

Initiation of a regimen containing LDV

ritonavir-boosted Paritaprevir/ Ombitasvir

Intervention Type DRUG

Initiation of a drug combination of PTV/OTV

Dasabuvir

Intervention Type DRUG

Initiation of a regimen containing DBV

Velpatasvir

Intervention Type DRUG

Initiation of a regimen containing VPV

Elbasvir

Intervention Type DRUG

Initiation of a regimen containing EBV

Grazoprevir

Intervention Type DRUG

Initiation of a regimen containing GZR

Interventions

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Telaprevir

Initiation of a regimen containing TVR

Intervention Type DRUG

Boceprevir

Initiation of a regimen containing BOC

Intervention Type DRUG

Sofosbuvir

Initiation of a regimen containing SOF

Intervention Type DRUG

Simeprevir

Initiation of a regimen containing SMV

Intervention Type DRUG

Daclatasvir

Initiation of a regimen containing DCV

Intervention Type DRUG

Ledipasvir

Initiation of a regimen containing LDV

Intervention Type DRUG

ritonavir-boosted Paritaprevir/ Ombitasvir

Initiation of a drug combination of PTV/OTV

Intervention Type DRUG

Dasabuvir

Initiation of a regimen containing DBV

Intervention Type DRUG

Velpatasvir

Initiation of a regimen containing VPV

Intervention Type DRUG

Elbasvir

Initiation of a regimen containing EBV

Intervention Type DRUG

Grazoprevir

Initiation of a regimen containing GZR

Intervention Type DRUG

Other Intervention Names

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TVR BOC SOF SMV DCV LDV PTV/OTV DBV VPV EBV GZR

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital del SAS de Jerez

OTHER

Sponsor Role collaborator

Hospital General Universitario Elche

OTHER

Sponsor Role collaborator

Hospital La Línea de la Concepción

UNKNOWN

Sponsor Role collaborator

Complexo Hospitalario Universitario de A Coruña

OTHER

Sponsor Role collaborator

Hospital de Figueres

UNKNOWN

Sponsor Role collaborator

Hospital Universitario Puerto Real

OTHER

Sponsor Role collaborator

Hospital Universitario Virgen de la Victoria

OTHER

Sponsor Role collaborator

Hospital Universitario de Canarias

OTHER

Sponsor Role collaborator

Hospital General Universitario de Alicante

OTHER

Sponsor Role collaborator

Hospital Universitario Araba

OTHER

Sponsor Role collaborator

Hospital Royo Vilanova

UNKNOWN

Sponsor Role collaborator

Hospital Universitario de Burgos

OTHER

Sponsor Role collaborator

Complejo Hospitalario Universitario de Huelva

OTHER

Sponsor Role collaborator

Hospital Universitario Reina Sofia de Cordoba

OTHER_GOV

Sponsor Role collaborator

Hospital Universitario Virgen Macarena

OTHER

Sponsor Role collaborator

Complejo Hospitalario Universitario de Vigo

OTHER

Sponsor Role collaborator

Clinica Universidad de Navarra, Universidad de Navarra

OTHER

Sponsor Role collaborator

Hospital Clinico Universitario San Cecilio

OTHER

Sponsor Role collaborator

Hospital Universitario La Fe

OTHER

Sponsor Role collaborator

Hospital General Universitario de Valencia

OTHER

Sponsor Role collaborator

Hospital Universitario Infanta Leonor

OTHER

Sponsor Role collaborator

Hospital Universitario de Gran Canaria

UNKNOWN

Sponsor Role collaborator

Hospital General Universitario Santa Lucía

OTHER

Sponsor Role collaborator

Centro Penitenciario Alicante 1

UNKNOWN

Sponsor Role collaborator

Hospital Regional Universitario Carlos Haya

OTHER

Sponsor Role collaborator

Hospital Virgen de la Luz

OTHER

Sponsor Role collaborator

Hospital General Universitario de Castellón

OTHER

Sponsor Role collaborator

Parc Taulí Hospital Universitari

OTHER

Sponsor Role collaborator

Valme University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Karin Neukam

Dr

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Karin I Neukam, Dr

Role: PRINCIPAL_INVESTIGATOR

Valme University Hospital

Locations

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Valme University Hospital

Seville, Andalusia, Spain

Site Status

Countries

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Spain

References

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Mancebo M, Real LM, Mira JA, Recio E, Perez E, Monje-Agudo P, Merchante N, Macias J, Neukam K, Pineda JA. Changes in the response to treatment against chronic hepatitis C between 1999 and 2015: data from a prospective cohort. Eur J Gastroenterol Hepatol. 2016 Nov;28(11):1253-7. doi: 10.1097/MEG.0000000000000705.

Reference Type RESULT
PMID: 27415157 (View on PubMed)

Macias J, Monge P, Mancebo M, Merchante N, Neukam K, Real LM, Pineda JA. High frequency of potential interactions between direct-acting antivirals and concomitant therapy in HIV/hepatitis C virus-coinfected patients in clinical practice. HIV Med. 2017 Aug;18(7):445-451. doi: 10.1111/hiv.12471. Epub 2016 Nov 24.

Reference Type RESULT
PMID: 27882706 (View on PubMed)

Neukam K, Morano-Amado LE, Rivero-Juarez A, Macias J, Granados R, Romero-Palacios A, Marquez M, Merino D, Ortega E, Alados-Arboledas JC, Cucurull J, Omar M, Ryan-Murua P, Pineda JA; Grupo de Estudio de Hepatitis Virica, of the Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica: GEHEP-SEIMC and Grupo de Estudio de Hepatitis Virica, of the Sociedad Andaluza de Enfermedades Infecciosas y Microbiologia Clinica: HEPAVIR/Red de Investigacion en SIDA (RIS-HEP07). Liver stiffness predicts the response to direct-acting antiviral-based therapy against chronic hepatitis C in cirrhotic patients. Eur J Clin Microbiol Infect Dis. 2017 May;36(5):853-861. doi: 10.1007/s10096-016-2871-x. Epub 2016 Dec 21.

Reference Type RESULT
PMID: 28004322 (View on PubMed)

Pineda JA, Morano-Amado LE, Granados R, Macias J, Tellez F, Garcia-Deltoro M, Rios MJ, Collado A, Delgado-Fernandez M, Suarez-Santamaria M, Serrano M, Miralles-Alvarez C, Neukam K; Grupo de Estudio de Hepatitis Virica, of the Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica: GEHEP-SEIMC; Grupo de Estudio de Hepatitis Virica, of the Sociedad Andaluza de Enfermedades Infecciosas y Microbiologia Clinica: HEPAVIR / Red de Investigacion en SIDA (RIS-HEP07). Week 4 response predicts sustained virological response to all-oral direct-acting antiviral-based therapy in cirrhotic patients with hepatitis C virus genotype 3 infection. Clin Microbiol Infect. 2017 Jun;23(6):409.e5-409.e8. doi: 10.1016/j.cmi.2016.12.034. Epub 2017 Jan 28.

Reference Type RESULT
PMID: 28137633 (View on PubMed)

Neukam K, Morano-Amado LE, Rivero-Juarez A, Mancebo M, Granados R, Tellez F, Collado A, Rios MJ, de Los Santos-Gil I, Reus-Banuls S, Vera-Mendez F, Geijo-Martinez P, Montero-Alonso M, Suarez-Santamaria M, Pineda JA. HIV-coinfected patients respond worse to direct-acting antiviral-based therapy against chronic hepatitis C in real life than HCV-monoinfected individuals: a prospective cohort study. HIV Clin Trials. 2017 May;18(3):126-134. doi: 10.1080/15284336.2017.1330801.

Reference Type RESULT
PMID: 28599618 (View on PubMed)

Alvarez-Ossorio MJ, Sarmento E Castro R, Granados R, Macias J, Morano-Amado LE, Rios MJ, Merino D, Alvarez EN, Collado A, Perez-Perez M, Tellez F, Martin JM, Mendez J, Pineda JA, Neukam K; HEPAVIR-DAA, GEHEP-MONO, RIS-HEP07 and RIS-HEP13 Study Groups. Impact of interferon-free regimens on the glomerular filtration rate during treatment of chronic hepatitis C in a real-life cohort. J Viral Hepat. 2018 Jun;25(6):699-706. doi: 10.1111/jvh.12867. Epub 2018 Feb 27.

Reference Type RESULT
PMID: 29377515 (View on PubMed)

Gonzalez-Serna A, Corma-Gomez A, Tellez F, Corona-Mata D, Rios-Villegas MJ, Merino D, Galera C, Collado-Romacho AR, De Los Santos I, Cucurull J, Santos M, Garcia-Martin S, Rivero A, Real LM, Macias J. Response to glecaprevir/pibrentasvir in HIV/HCV-coinfected patients in clinical practice. J Antimicrob Chemother. 2023 Oct 3;78(10):2591-2596. doi: 10.1093/jac/dkad278.

Reference Type DERIVED
PMID: 37671831 (View on PubMed)

Macias J, Morano LE, Tellez F, Granados R, Rivero-Juarez A, Palacios R, Rios M, Merino D, Perez-Perez M, Collado A, Figueruela B, Morano A, Freyre-Carrillo C, Martin JM, Rivero A, Garcia F, Pineda JA; HEPAVIR group from the Sociedad Andaluza de Enfermedades Infecciosas (SAEI) and the GEHEP group from the Sociedad Espanola de Enfermedades Infecciosas y Microbiologia (SEIMC). Response to direct-acting antiviral therapy among ongoing drug users and people receiving opioid substitution therapy. J Hepatol. 2019 Jul;71(1):45-51. doi: 10.1016/j.jhep.2019.02.018. Epub 2019 Mar 8.

Reference Type DERIVED
PMID: 30853642 (View on PubMed)

Other Identifiers

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GEHEP-001

Identifier Type: OTHER

Identifier Source: secondary_id

GEHEP-MONO

Identifier Type: -

Identifier Source: org_study_id

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