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

This study is currently recruiting participants.
Verified May 2013 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: May 21, 2013
Last verified: May 2013

April 20, 2011
May 21, 2013
April 2011
April 2017   (final data collection date for primary outcome measure)
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.
Changes of liver stiffness measurement (LSM) and hyaluronan measurement in blood [ Time Frame: 12 Month ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01341106 on ClinicalTrials.gov Archive Site
  • 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 ]
    Measurment 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 apperance of side effects of after 12 month treatment with entecavir(Baraclude®)within whole study period of 60 month.
  • Changes on Pro-Collagen-III-N-Peptid, Tissue Inhibitor of Metalloproteinases (TIMP-1) and YKL-40 in serum [ Time Frame: 12 Month ] [ Designated as safety issue: No ]
  • Sensitivity and specificity of non-invasive marker (LSM with FibroScan and serum parameter(hyaluronan measurement, Pro-Collagen-III-N-Peptid, TIMP-1 and YKL-40)) at the baseline in comparison to liver biopsy as a gold standard [ Time Frame: 12 Month ] [ Designated as safety issue: No ]
  • Changes on FibroScan-measurement (LSM) and serum parameter (hyaluronan measurement, Pro-Collagen-III-N-Peptid, TIMP-1 and YKL-40 ) at 6,12,18,24,36,48 and 60 month [ Time Frame: 6,12,18,24,36,48 and 60 month ] [ Designated as safety issue: No ]
  • 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 ]
  • Quota of patients with normalization of 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 HBeAg loss, anti-HBe seroconversion, HBsAg loss and anti-HBs seroconversion at separate timepoint [ Time Frame: 6,12, 18, 24, 32, 48 and 60 month ] [ Designated as safety issue: No ]
  • Incidence of side effects [ Time Frame: whole study period ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Induction of Fibrosis Regression on Patients With Chronic Hepatitis B Infection
Induction of Fibrosis Regression on Patients With Chronic Hepatitis B Infection

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.

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.

Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
  • Hepatitis B, Chronic
  • Liver Fibrosis
Drug: Treatment with entecavir(Baraclude®)
Patient will be daily treated with 1 tablet of entecavir per oral
Experimental: Treatment Arm
Patients will be treated wwith entecavir
Intervention: Drug: Treatment with entecavir(Baraclude®)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
April 2017
April 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • chronic hepatitis B infection with detectable HBV-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> 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, 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
Both
18 Years to 75 Years
No
Contact: Hermann Wasmuth, PD MD +49 241 80 ext 80861 hwasmuth@ukaachen.de
Germany
 
NCT01341106
CTC-A 11-018, 2010-019884-12, 11-018
No
RWTH Aachen University
RWTH Aachen University
  • Hannover Medical School
  • Hannover Clinical Trial Center GmbH
Principal Investigator: Christian Trautwein, Professor MD Department of Internal Medicine III, University Hospital Aachen
RWTH Aachen University
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP