Induction of Fibrosis Regression on Patients With Chronic Hepatitis B Infection (INFIRE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by RWTH Aachen University
Sponsor:
Collaborators:
Hannover Medical School
Hannover Clinical Trial Center GmbH
Information provided by (Responsible Party):
RWTH Aachen University
ClinicalTrials.gov Identifier:
NCT01341106
First received: April 20, 2011
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

This study will examine whether 12 month treatment with entecavir(Baraclude®) has an effect on changes of liver stiffness measurement (LSM) and of hyaluronan measurement in patients with chronic hepatitis B infection.


Condition Intervention Phase
Hepatitis B, Chronic
Liver Fibrosis
Drug: Treatment with entecavir(Baraclude®)
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Induction of Fibrosis Regression on Patients With Chronic Hepatitis B Infection

Resource links provided by NLM:


Further study details as provided by RWTH Aachen University:

Primary Outcome Measures:
  • Changes of liver stiffness measurement (LSM) and hyaluronan measurement in blood [ Time Frame: 12 Month ] [ Designated as safety issue: No ]
    Changes of liver stiffness measurement (LSM) and hyaluronan measurement in blood will be checked as markers of fibrous tissue in the liver after treatment with entecavir(Baraclude®) within 12 month.


Secondary Outcome Measures:
  • Changes on Pro-Collagen-III-N-Peptid, Tissue Inhibitor of Metalloproteinases (TIMP-1) and Chitinase-3-like protein 1(YKL-40) in serum [ Time Frame: 12 Month ] [ Designated as safety issue: No ]
    Changes on Pro-Collagen-III-N-Peptid, Tissue Inhibitor of Metalloproteinases (TIMP-1) and Chitinase-3-like protein 1(YKL-40) in serum will be checked after 12 month treatment.

  • Sensitivity and specificity of non-invasive marker at the baseline in comparison to liver biopsy as a gold standard [ Time Frame: 12 Month ] [ Designated as safety issue: No ]
    Non-invasive marker(liver stiffness measurement(LSM) with FibroScan and serum parameter(hyaluronan measurement, Pro-Collagen-III-N-Peptid, Tissue Inhibitor of Metalloproteinases(TIMP-1) and Chitinase-3-like protein 1(YKL-40))) at the baseline will be compared with results of liver biopsy as gold standard after treatment with entecavir(Baraclude®) within 12 month.

  • Changes on FibroScan-measurement (LSM) and serum parameter [ Time Frame: 6,12,18,24,36,48 and 60 month ] [ Designated as safety issue: No ]
    Changes on FibroScan-measurement (LSM) and serum parameter (hyaluronan measurement, Pro-Collagen-III-N-Peptid, Tissue Inhibitor of Metalloproteinases(TIMP-1) and Chitinase-3-like protein 1(YKL-40))) will be checked at timepoints of 6,12,18,24,36,48 and 60 month after treatment with entecavir(Baraclude®) within 12 month.

  • Decrease of hepatitis B virus-DNA and quota of patients with non-detectable hepatitis B virus-DNA at separate timepoints. [ Time Frame: 6, 12, 18, 24, 32, 48 and 60 month ] [ Designated as safety issue: No ]
    Measurement of decrease of hepatitis B virus-DNA and quota of patients with non-detectable hepatitis B virus-DNA at several timepoints after treatment with entecavir(Baraclude®) within 12 month.

  • Quota of patients with normalization of Alanine transaminase(ALT)-measurement in blood at separate timepoints [ Time Frame: 6,12, 18, 24, 32, 48 and 60 month ] [ Designated as safety issue: No ]
    Quota of patients with normalization of Alanine transaminase(ALT)-measurement in blood will be checked at separate timepoints after treatment with entecavir(Baraclude®) within 12 month.

  • Quota of patients with hepatitis B viral protein loss, antibodies to the the hepatitis B 'e' antigen seroconversion, surface antigen of the Hepatitis-B-Virus loss and antibodies to the hepatitis B core antigen seroconversion at separate timepoints [ Time Frame: 6,12, 18, 24, 32, 48 and 60 month ] [ Designated as safety issue: No ]
    Quota of patients with core antigen hepatitis B viral protein (HBeAg) loss, antibodies to the the hepatitis B 'e' antigen(anti-HBe) seroconversion, surface antigen of the Hepatitis-B-Virus(HBsAg) loss and antibodies to the hepatitis B core antigen(anti-HBs) seroconversion will be checked at separate timepoints after treatment with entecavir(Baraclude®) within 12 month.

  • Incidence of side effects [ Time Frame: 60 month ] [ Designated as safety issue: Yes ]
    Incidence of appearance of side effects of after 12 month treatment with entecavir(Baraclude®)within whole study period of 60 month.


Estimated Enrollment: 100
Study Start Date: April 2011
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment Arm
Patients will be treated with entecavir
Drug: Treatment with entecavir(Baraclude®)
Patient will be daily treated with 1 tablet of entecavir per oral

Detailed Description:

Patients with chronic hepatitis B infection and relevant liver fibrosis will be treated with entecavir during 5 years or until anti-HBs seroconversion or 6-12 months after anti-HBe seroconversion and HBeAg loss. There are 9 visits during treatment for each patient. At all visits, each patient will consent to give 20 ml blood sample for study examination and 40 ml blood sample for research purposes.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • chronic hepatitis B infection with detectable HBV (hepatitis B virus)-DNA at baseline
  • results of a current liver biopsy (date of liver biopsy must not be longer than 3 months as date of screening visit)
  • detection of relevant liver fibrosis in liver histology after percutaneous or laparoscopic biopsy (histologically ≥ F2) after estimation by an experienced pathologist in the liver pathology and sufficient evaluability of the biopsy (usually evaluation of portal at least 8 fields)
  • Therapy indication according to current guidelines cHBV infection ( any virus replication in the presence of liver cirrhosis, or detection of HBV-DNA ≥ 2000 IU / ml and/or liver histology with inflammatory Grade ≥2 / fibrosis stage 2 and presence of ALT <5 x ULN)
  • non-pregnant and non-breastfeeding women, who fitful one of following criteria: * post-menopausal (12 months natural amenorrhea or 6 months amenorrhea with serum FSH (follicle stimulating hormone)> 40mlU/ml)

    • 6 weeks after surgical sterilization by bilateral tubal transection or after bilateral oophorectomy with or without hysterectomy
    • Correct application of two methods of sure contraception (any combination of a hormonal contraceptive (the pill, hormone IUD (intrauterine device), Depo-Provera, Implanon, contraceptive patch or vaginal ring) or IUD with a barrier contraceptive with spermicide (diaphragm, cervical cap, LEA contraceptive, female condoms or condom)or a spermicide.
    • Sexual abstinence for 2 weeks before the first administration of the study medication, during the study period and after the study during 30 days (time of elimination of study medication)
    • Patients, who have only female sexual partners
    • Male partner of a female patient, who before study inclusion, sterile and only one sexual partner of this female patient is
  • Patients willing and able to complete the requirements of this study

Exclusion Criteria:

  • anamnestic known hypersensitivity to Baraclude® or its ingredients or to drugs with similar chemical structure
  • Participation of patients in another clinical study within last 4 weeks prior to the inclusion or simultaneous participation in another clinical study
  • anamnestic known substance dependance or another diseases, which not allowed persons to understand essence and importance and possible consequences of the trial
  • lack of cooperation and informed consent
  • co-infection with hepatitis C, hepatitis D or HIV
  • detection of hepatocellular carcinoma
  • serious, chronic disease with an estimated prognosis for survival shorter than the study period of 5 years
  • every previous therapy with lamivudine or telbivudine or previous therapy with other antiviral substance within last 6 months before study inclusion
  • contraindications to the use of entecavir
  • creatinine clearance <50 ml / min and / or need for hemodialysis
  • MELD score >15 points and / or detection of ascites
  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: NCT01341106

Contacts
Contact: Hermann Wasmuth, PD MD +49 241 80 ext 80861 hwasmuth@ukaachen.de

Locations
Germany
Department of Internal Medicin III, University Hospital Aachen Recruiting
Aachen, NRW, Germany, 52074
Contact: Christian Trautwein, Professor MD    +49 241 80 ext 80866    ctrautwein@ukaachen.de   
Contact: Hermann Wasmuth, PD MD    +49 241 80 ext 80861    hwasmuth@ukaachen.de   
Principal Investigator: Christian Trautwein, Professor MD         
Sponsors and Collaborators
RWTH Aachen University
Hannover Medical School
Hannover Clinical Trial Center GmbH
Investigators
Principal Investigator: Christian Trautwein, Professor MD Department of Internal Medicine III, University Hospital Aachen
  More Information

No publications provided

Responsible Party: RWTH Aachen University
ClinicalTrials.gov Identifier: NCT01341106     History of Changes
Other Study ID Numbers: CTC-A 11-018, 2010-019884-12, 11-018
Study First Received: April 20, 2011
Last Updated: June 6, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by RWTH Aachen University:
chronic hepatitis B
liver fibrosis
treatment with Entecavir

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Hepatitis, Viral, Human
Fibrosis
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Liver Diseases
Pathologic Processes
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