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

Chronic Hepatitis C Infection Clinical Trial

— FPSMON201401  

Official title:

Efficacy and Safety of Treatment Against Hepatitis C Virus Infection Based on Direct-acting Antivirals in Real-life Conditions: The GEHEP Cohort

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02333292
• Other study ID #: GEHEP-MONO
• Secondary ID: GEHEP-001
• Status: Completed
• Start date: December 2014
• Est. completion date: June 30, 2017

Study information

• Verified date: June 2022
• Source: Valme University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1128
• Est. completion date: June 30, 2017
• Est. primary completion date: December 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis C Infection
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Infections

Intervention

Drug:
• Telaprevir
Initiation of a regimen containing TVR
• Boceprevir
Initiation of a regimen containing BOC
• Sofosbuvir
Initiation of a regimen containing SOF
• Simeprevir
Initiation of a regimen containing SMV
• Daclatasvir
Initiation of a regimen containing DCV
• Ledipasvir
Initiation of a regimen containing LDV
• ritonavir-boosted Paritaprevir/ Ombitasvir
Initiation of a drug combination of PTV/OTV
• Dasabuvir
Initiation of a regimen containing DBV
• Velpatasvir
Initiation of a regimen containing VPV
• Elbasvir
Initiation of a regimen containing EBV
• Grazoprevir
Initiation of a regimen containing GZR

Locations

Country	Name	City	State
Spain	Valme University Hospital	Seville	Andalusia

Sponsors (29)

Lead Sponsor

Collaborator

Valme University Hospital

Centro Penitenciario Alicante 1, Clinica Universidad de Navarra, Universidad de Navarra, Complejo Hospitalario Universitario de Huelva, Complejo Hospitalario Universitario de Vigo, Complexo Hospitalario Universitario de A Coruña, Hospital Clinico Universitario San Cecilio, Hospital de Figueres, Hospital del SAS de Jerez, Hospital General Universitario de Alicante, Hospital General Universitario de Castellón, Hospital General Universitario de Valencia, Hospital General Universitario Elche, Hospital General Universitario Santa Lucía, Hospital La Línea de la Concepción, Hospital Parc Taulí, Sabadell, Hospital Regional Universitario Carlos Haya, Hospital Royo Vilanova, Hospital Universitario Araba, Hospital Universitario de Burgos, Hospital Universitario de Canarias, Hospital Universitario de Gran Canaria, Hospital Universitario Infanta Leonor, Hospital Universitario La Fe, Hospital Universitario Puerto Real, Hospital Universitario Reina Sofia de Cordoba, Hospital Universitario Virgen de la Victoria, Hospital Universitario Virgen Macarena, Hospital Virgen de la Luz

Country where clinical trial is conducted

Spain, 

References & Publications (6)

Álvarez-Ossorio MJ, Sarmento E Castro R, Granados R, Macías J, Morano-Amado LE, Ríos MJ, Merino D, Álvarez EN, Collado A, Pérez-Pérez M, Téllez F, Martín JM, Méndez J, Pineda JA, Neukam K; HEPAVIR-DAA, GEHEP-MONO, RIS-HEP07 and RIS-HEP13 Study Groups. Imp — View Citation

Macías 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 — View Citation

Mancebo M, Real LM, Mira JA, Recio E, Pérez E, Monje-Agudo P, Merchante N, Macías 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. — View Citation

Neukam K, Morano-Amado LE, Rivero-Juárez A, Macías J, Granados R, Romero-Palacios A, Márquez M, Merino D, Ortega E, Alados-Arboledas JC, Cucurull J, Omar M, Ryan-Murua P, Pineda JA; Grupo de Estudio de Hepatitis Vírica, of the Sociedad Española de Enferme — View Citation

Neukam K, Morano-Amado LE, Rivero-Juárez A, Mancebo M, Granados R, Téllez F, Collado A, Ríos MJ, de Los Santos-Gil I, Reus-Bañuls S, Vera-Méndez F, Geijo-Martínez P, Montero-Alonso M, Suárez-Santamaría M, Pineda JA. HIV-coinfected patients respond worse t — View Citation

Pineda JA, Morano-Amado LE, Granados R, Macías J, Téllez F, García-Deltoro M, Ríos MJ, Collado A, Delgado-Fernández M, Suárez-Santamaría M, Serrano M, Miralles-Álvarez C, Neukam K; Grupo de Estudio de Hepatitis Vírica, of the Sociedad Española de Enfermed — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Patients with Sustained Virological Response	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.	48 weeks
Primary	Number of Participants with Adverse Events	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.	48 weeks
Secondary	Identification of predictors of SVR		48 weeks
Secondary	Analyze efficacy and safety in patients that receive methadone maintenance therapy		48 weeks
Secondary	Analyze efficacy and safety according to previous treatment outcome		48 weeks
Secondary	Analyze efficacy and safety in patients with cirrhosis		48 weeks
Secondary	Evaluate impact of SVR on biological, elastographical and clinical parameters		48 hours