Entecavir for Chronic Hepatitis B

This study has been completed.
Sponsor:
Information provided by:
Foundation for Liver Research
ClinicalTrials.gov Identifier:
NCT01323452
First received: March 21, 2011
Last updated: March 24, 2011
Last verified: March 2011
  Purpose

The primary aim of this study is to asses the efficacy (both virological and clinical) and safety of ETV in both NA-naïve and NA-experienced chronic hepatitis B patients, and to explore baseline factors associated with virologic reponse (VR) to ETV.


Condition Intervention
Entecavir for Chronic Hepatitis B Patients
Drug: Entecavir

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: The Antiviral Efficacy of Entecavir in Chronic Hepatitis B Within the European Network of Excellence (VIRGIL)

Resource links provided by NLM:


Further study details as provided by Foundation for Liver Research:

Primary Outcome Measures:
  • Virological response [ Time Frame: 144 weeks after starting Entecavir ] [ Designated as safety issue: No ]
    Cumulative probability (%) of patients achieving HBV DNA negativity at week 144


Enrollment: 418
Study Start Date: November 2010
Study Completion Date: March 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Chronic HBV patients
Patients with chronic hepatitis B Treated for at least 3 months No HIV, HCV or HDV.
Drug: Entecavir
once daily

Detailed Description:

Chronic hepatitis B is a major health problem, affecting more than 350 million people worldwide. (1) First line treatment consists of pegylated IFN once weekly or oral nucleos(t)ide analogues (NA) once daily. (2) NA target the reverse transcriptase of hepatitis B virus (HBV), and are potent inhibitors of viral replication. In the absence of antiviral drug resistance, continued NA therapy is able to suppress viral replication over prolonged periods, and can prevent clinical progression to liver cirrhosis and hepatocellular carcinoma. (3) Currently approved agents include the nucleoside analogues lamivudine (LAM), telbivudine (LdT), and entecavir (ETV), and the nucleotide analogues adefovir dipivoxil (ADV), and tenofovir disiproxil fumarate (TDF).

Entecavir ETV is a cyclopentyl guanosine analogue, and a potent and selective inhibitor of HBV replication in vitro.(4) In the phase III registration trials it resulted in superior virologic, biochemical and histological efficacy after one year of therapy compared to LAM in both HBeAg-positive and HBeAg-negative chronic HBV patients. (5, 6) Moreover, ETV proved to have a high genetic barrier to resistance with only 1.2% of NA-naïve HBV patients demonstrating genotypic resistance to ETV after five years of ETV monotherapy.(7) In LAM-refractory chronic HBV patients ETV appeared to be less potent and the frequency of resistance was increased. (8, 9) After five years of treatment 51% of LAM-refractory patients showed genotypic ETV resistance, and in 43% a virologic breakthrough was observed as well. (7) Recently we presented the promising results of a large European cohort of patients treated with ETV for a median period of 12 months. We concluded that ETV should not be used in patients with a prior history of LAM-resistance. However, prior treatment with ADV did not influence the efficacy of ETV in these patients.(10)

HBeAg loss or seroconversion In HBeAg positive patients, HBeAg loss or seroconversion is the major objective of NA treatment regimes according to current guidelines. HBeAg loss or seroconversion is usually associated with sustained remission and a very low risk for the development of cirrhosis and hepatocellular carcinoma. (11-13) PEG-IFN induced HBeAg seroconversion was shown to be sustained in 70% after a 3 year follow up. (14) There are some contradictory results concerning NA induced durability of HBeAg loss or seroconversion. First reports on lamuvidine induced HBeAg loss or seroconversion were rather promising.(15-17) However, more recent and also larger studies report much higher relapse rates and predictors of sustainability were proposed. (18-21) The registration trial of entecavir showed a 82% durability after 24 weeks without consolidation therapy.(6) Recently we showed that the durability of HBeAg seroconversion was very poor with 42%, 58% and 74% seroreversion respectively 1,2 and 3 years after seroconversion on different NA treatment regimes. However, only a minority of these patients was treated with the newer and more potent NA. (22)

As the increasing number of patients who experienced treatment failure to different NA treatment regimens poses a growing problem for the clinician, data on the efficacy of ETV in these NA-experienced patient groups is warranted. Furthermore, current guidelines are subject of discussion as durability of NA induced HBeAg loss or seroconversion seems less sustained then expected, and prolonged or maybe infinite therapy may be necessary to prevent long term complications.

  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 consecutive adult CHB patients treated with ETV monotherapy in 10 large European referral centers

Criteria

Inclusion Criteria:

  • HBsAg positive for at least 6 months
  • Entecavir therapy for at least 3 months

Exclusion Criteria:

  • viral co infections
  • concomitant antiviral therapy
  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: NCT01323452

Locations
Netherlands
Erasmus Mc
Rotterdam, Netherlands, 3015 CE
Sponsors and Collaborators
Foundation for Liver Research
Investigators
Principal Investigator: Harry LA Janssen, MD, PhD Erasmus MC
  More Information

No publications provided

Responsible Party: Prof. Dr. H.L.A. Janssen, Foundation for Liver and Gastrointestinal Research (SLO)
ClinicalTrials.gov Identifier: NCT01323452     History of Changes
Other Study ID Numbers: VIRGIL
Study First Received: March 21, 2011
Last Updated: March 24, 2011
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Foundation for Liver Research:
entecavir
hepatitis B

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Entecavir
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014