Real-life Security and Efficacy of DAA-based Therapy in HCV/HIV-Coinfected Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Valme University Hospital
Sponsor:
Collaborators:
Hospital Universitario Reina Sofia
Hospital Universitario Virgen de la Victoria
Hospital Universitario de la Princesa
Hospitales Universitarios Virgen del Rocío
Hospital Universitario Carlos Haya
Hospital Torrecárdenas
Complejo Hospitalario de Huelva
Hospital Puerta del Mar
Virgen de la Macarena University Hospital
Hospital de La Línea
Information provided by (Responsible Party):
José A. Mira Escarti, Valme University Hospital
ClinicalTrials.gov Identifier:
NCT02057003
First received: January 6, 2014
Last updated: February 5, 2014
Last verified: January 2014
  Purpose

The purpose of this study is to evaluate the efficacy and tolerability of DAA-based regimens in the clinical practice in HIV/HCV-coinfected patients.

Hypothesis: The efficacy and tolerability of DAA-based regimens in the clinical practice is different to what is observed in clinical trials in HIV/HCV-coinfected patients.


Condition Intervention
Hepatitis C, Chronic
Human Immunodeficiency Virus
Drug: DAA against HCV

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Security and Efficacy of Triple Therapy Including Direct-Acting Antivirals Against Chronic Hepatitis C Infection In HIV-Coinfected Patients In Real-Life Conditions: The Prospective HEPAVIR Cohort.

Resource links provided by NLM:


Further study details as provided by Valme University Hospital:

Primary Outcome Measures:
  • Number of patients who achieve SVR to DAA-based therapy as measure of efficacy [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Achievement of SVR to DAA-based therapy in the clinical practice in patients with chronic hepatitis C and HIV coinfection.

  • Number of patients who develop severe adverse events as measure of safety [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    Development of severe adverse events related to DAA-based therapy in the clinical practice in patients with chronic hepatitis C and HIV coinfection.


Secondary Outcome Measures:
  • Number of patients who achieve SVR to a BOC-based regimen as compared to numbers of patients who achieve SVR to a TVR-based regimen. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    In order to compare TVR- and BOC-based therapy, the numbers of patients who achieve SVR to DAA-based therapy will be analyzed.

  • Number of patients who reach undetectable HCV-RNA at week 4 of PI-based therapy as a measure of on-treatment response to therapy. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Number of patients who develop adverse events during a BOC-based regimen as compared to numbers of patients who develop adverse events during a TVR-based regimen. [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    In order to compare TVR- and BOC-based therapy, the numbers of patients who develop adverse events during either treatment will be analyzed.


Estimated Enrollment: 230
Study Start Date: January 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
DAA-based therapy against HCV
HIV/HCV-coinfected patients who start triple therapy against HCV including a DAA for the the first time.
Drug: DAA against HCV
Other Names:
  • telaprevir
  • boceprevir

  Hide Detailed Description

Detailed Description:

Treatment strategies aimed to achieve sustained virologic response (SVR) are of highest priority in patients with chronic hepatitis C and HIV coinfection, since SVR leads to a dramatic reduction in the incidence of hepatic decompensations and mortality in this setting. Until recently, therapy against hepatitis C virus (HCV) was based on pegylated interferon (peg-IFN) plus ribavirin (RBV). This combination prompt SVR only in approximately 50% of the HCV genotype 1 (HCV-1)-infected patients. Furthermore, it is costly and associated with multiple and sometimes serious side effects. In the setting of HIV/HCV-1-coinfection, rates of SVR are even lower and do not exceed 25% in the clinical practice.

Considerable increases of SVR have been achieved recently with the arrival of direct acting antivirals (DAA) against HCV. Among the first of these new agents are the protease inhibitors telaprevir (TVR) and boceprevir (BOC), which are approved for HCV-1 infection. Data obtained from clinical trials have demonstrated that the combination of peg-IFN/RBV with TVR or BOC significantly augments SVR rates as compared to what is observed with peg-IFN plus RBV only. As a consequence, triple therapy including peg-IFN, RBV plus TVR or BOC has become the standard therapy for HCV-1-infected patients in our setting. In addition, a number of further DAAs are currently in the final phases of development, as it is the case for the protease inhibitors faldaprevir and simeprevir, the polymerase NS5B inhibitor sofosbuvir and the NS5A inhibitor daclatasvir.

Although the considerable improvement of therapy outcome with DAA-including regimens is giving a positive prospective, there are a number of questions that have to be solved as soon as possible. On the one hand, the information on response to DAA in the coinfected population is derived from clinical trials, which often do not reflect patient management in the clinical practice. Also, the populations included in clinical trials are highly selective and may lack the high proportion of difficult-to-treat individuals expected among the candidate population, i.e., those who failed previous treatment and who bear compensated cirrhosis. In fact, data derived from the French cohort CUPIC including HCV-monoinfected, cirrhotic patients, show that tolerability and efficacy of TVR and BOC-based treatment is lower than observed in pivotal trials. On the other hand, similar to dual therapy including Peg-IFN/RBV, it is possible that both response rates and safety profiles of DAAs are not comparable between HCV-monoinfected and HIV/HCV-coinfected patients. In this context, the coinfected population has singularities as the coadministration of antiretroviral therapy, that may cause drug-drug-interactions and decreased tolerability, thus resulting in diminished efficacy. Finally, it is of highest relevance to identify predictive factors for treatment response in the new DAA-based regimens in order to individualize treatment decision and duration of therapy.

Due to the above mentioned, studies on safety and efficacy of DAA-based therapy under real life conditions in HIV/HCV-coinfected patients are urgently needed.

Primary objectives:

  • To determine the efficacy of DAA-based therapy in the clinical in patients with chronic hepatitis C and HIV coinfection.
  • To determine the security of DAA-based therapy in the clinical in patients with chronic hepatitis C and HIV coinfection.

Secondary objectives:

  • Identification of predictive factors for response to DAA-based treatment in the studied population.
  • Compare security and efficacy of the different DAAs used.
  • Evaluate the on-treatment HCV kinetics for the different regimens.

Scheduled visits: 0, 1, 2, 4, 8, 12, 24, 36 and 48 weeks, as well as 12 and 24 weeks post-treatment.

Definition SVR: Undetectable HCV-RNA 24 weeks after scheduled end of treatment.

Definition of hepatic fibrosis:

  • advanced fibrosis: F3 as determined by liver biopsy or 11 kilopascals as determined by transient elastometry
  • cirrhosis: F4 as determined by liver biopsy or 14.6 kilopascals as determined by transient elastometry

Variables collected within in the cohort:

  • primary outcome variable: SVR (efficacy study) and % of patients who discontinued therapy due to adverse events (safety study)
  • epidemiological variable: age, sex, interleukin 28B rs12979860 genotype
  • variables related to hepatitis C virus-infection: infection route, genotype, grade of hepatic fibrosis and method used for its determination, baseline Child-Pough-Index, previous hepatic decompensations
  • treatment-related variables: previous response to treatment, doses and dose reductions/discontinuations of peg-IFN, RBV and the DAA(s), overall severe adverse events, adverse events that occur in more than 5% of the patients, hepatic decompensations, deaths, HCV viral load at baseline and at each visit
  • variables related to HIV-infection: Centers for Disease Control and Prevention (CDC) category, HIV viral load, cluster of differentiation 4 (CD4) cell count, antiretroviral regimen
  • analytical variables: aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelets, leucocytes, low-density lipoprotein cholesterol, bilirubin, gamma-glutamyltransferase (GGT), alkaline phosphatase,
  • clinical variables: alcohol intake Quality assurance and data checks: Data will be obtained from controlled databases at the participating centers. Databases will be monitored and controlled by queries every three months. Descriptive statistics will be be applied in order to detect transcription errors.

Source data verification: not planned.

All grade 3 or 4 adverse events, as well as all unexpected events, will be reported to the Andalusian Center for Pharmacovigilance (Centro Andaluz de Farmacovigilancia, www.cafv.es).

A sample size of 230 is planned for this study.

Statistical analysis: The outcome variables of this study will be the achievement of SVR, as well as the development of severe adverse events during follow-up. Descriptive statistical analysis will be performed in order to describe the cohort. Continuous variables will be expressed as median [interquartile range (IQR)] and categorical variables as number [percentage; 95% confidence interval (CI)]. The association of continuous variables with SVR or the frequency of patients who discontinue therapy will be analyzed using the Student's t-test for normal distribution and the Mann-Whitney U-test otherwise whereas the relationship with categorical variables will be determined applying the χ2-test or the Fisher's test, when applicable. Those factors that show an association in the univariate analysis with a p<0.2, as well as those with a biologically possible influence, will be entered logistic regression in order to identify independent predictors for SVR. The adjusted odds ratio (AOR) and the respective 95% CI will be calculated. All p values <0.05 will be considered statistically significant. Data will be analyzed using the SPSS statistical software package release 19.0 (SPSS Inc., Chicago, Illinois, USA) and STATA 9.0 (StataCorp, College Station, Texas, USA).

Sample size calculations: Estimating a SVR rate of 55%, with a confidence interval of 95% and a lost-to-follow-up rate of 5%, a minimum of 230 patients should be included in order to obtain a precision of 5%.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

All patients who consecutively attend the Unit of Infectious Diseases of the Study Group for Viral Hepatitis (HEPAVIR) of the Andalusian Society of Infectious Diseases (Sociedad Andaluza de Enfermedades Infecciosas, SAEI), Spain, will be considered for this study.

Criteria

Inclusion Criteria:

  • Older than 18 years
  • HIV infection determined by enzymeimmunoassay and confirmed by Western Blot
  • Naïve to treatment including a DAA
  • Initiation of triple therapy including a DAA
  • Written informed consent to participate in the study and to undergo genetic determinations

Exclusion Criteria:

  • Pregnancy
  • Any contraindication for the administration of peg-IFN, RBV or the respective DAA
  • Patients who are not able to provide informed consent to participate in the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02057003

Contacts
Contact: José A Mira Escarti, MD 0034955015684 miraescarti@yahoo.es

Locations
Spain
Valme University Hospital Recruiting
Seville, Spain, 41014
Contact: José A Mira Escarti, MD    0034955015684    miraescarti@yahoo.es   
Contact: Karin I Neukam, PhD    0034955015871    karin.neukam@gmail.com   
Sponsors and Collaborators
Valme University Hospital
Hospital Universitario Reina Sofia
Hospital Universitario Virgen de la Victoria
Hospital Universitario de la Princesa
Hospitales Universitarios Virgen del Rocío
Hospital Universitario Carlos Haya
Hospital Torrecárdenas
Complejo Hospitalario de Huelva
Hospital Puerta del Mar
Virgen de la Macarena University Hospital
Hospital de La Línea
Investigators
Principal Investigator: José A Mira Escarti, MD Valme University Hospital
  More Information

Publications:

Responsible Party: José A. Mira Escarti, MD, Valme University Hospital
ClinicalTrials.gov Identifier: NCT02057003     History of Changes
Other Study ID Numbers: HEPAVIR-DAA
Study First Received: January 6, 2014
Last Updated: February 5, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Valme University Hospital:
HIV
hepatitis C virus
sustained virologic response
telaprevir
boceprevir
simeprevir
sofosbuvir
daclatasvir
faldaprevir
pegylated interferon
ribavirin
direct-acting antivirals

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Lentivirus Infections
Retroviridae Infections
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Hepatitis, Chronic

ClinicalTrials.gov processed this record on September 22, 2014