Tenofovir in Chronic Hepatitis B With Mild ALT Elevation

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by E-DA Hospital
Sponsor:
Collaborators:
Gilead Sciences
Taipei Institute of Pathology, Taiwan
Information provided by (Responsible Party):
Hung Chi Chen, E-DA Hospital
ClinicalTrials.gov Identifier:
NCT01522625
First received: January 27, 2012
Last updated: October 14, 2012
Last verified: October 2012
  Purpose

This study aims to clarify whether patients with chronic hepatitis B with high viral load will benefit from oral antiviral therapy despite only mildly elevated serum liver enzyme.


Condition Intervention Phase
Chronic Hepatitis B
Drug: tenofovir disoproxil fumarate 300mg per day
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients With High Viral Load But Slight Aminotransferase Elevation

Resource links provided by NLM:


Further study details as provided by E-DA Hospital:

Primary Outcome Measures:
  • Severity of hepatic necroinflammation and fibrosis [ Time Frame: Within one month after completion of antiviral therapy ] [ Designated as safety issue: No ]
    Primary outcome is the severity of necroinflammation and fibrosis in liver tissue as evaluated by Knodell and Ishak scoring system


Secondary Outcome Measures:
  • Undetectable hepatitis B viral DNA [ Time Frame: Within one month after completion of antiviral therapy ] [ Designated as safety issue: No ]
    HBV DNA viral DNA not detected in serum

  • Normalization of serum alanine aminotransferase [ Time Frame: Within one month after completion of antiviral therapy ] [ Designated as safety issue: No ]
    serum ALT <40 IU/mL

  • Serum level of HBsAg [ Time Frame: Within one month after completion of antiviral therapy ] [ Designated as safety issue: No ]
    quantification of serum HBV serface antigen

  • Serious adverse reaction [ Time Frame: Within one month after completion of antiviral therapy ] [ Designated as safety issue: Yes ]
    Defined as death, life threatening event, permanent or temporary disability, and hospitalization


Estimated Enrollment: 160
Study Start Date: January 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TDF
tenofovir disoproxil fumarate (TDF) 300mg
Drug: tenofovir disoproxil fumarate 300mg per day
tenofovir disoproxil fumarate 300mg per day for 3 years
Other Name: Viread® (Gilead Sciences Inc)
Placebo Comparator: Placebo Drug: Placebo
Placebo, identical to TDF in appearance, once daily for 3years

Detailed Description:

Chronic hepatitis B (CHB) is a serious disease in Taiwan, leading to substantial morbidity and mortality including hepatic failure, liver cirrhosis, and hepatocellular carcinoma (HCC). Recently a large body of evidence supports that high level of serum HBV DNA is an independent risk factor for late complications in CHB patients. Nucleos(t)ide analogues (NUC) are effective antiviral therapy that can potently inhibit replication of hepatitis B virus (HBV), and has been widely used in management of patients with CHB. Current practice guidelines recommend using serum alanine aminotransferase (ALT) > 2 times of the upper limit of normal (ULN) as the prerequisite to initiate antiviral therapy in compensated CHB patients without liver cirrhosis. However, serum ALT level does not exactly correlate with serum HBV DNA or liver tissue injury. Whether antiviral therapy improves outcomes of patients with slightly elevated ALT (i.e. 1-2 folds of ULN) remains unknown.

  Eligibility

Ages Eligible for Study:   25 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age between 25 to 70 years,
  • serum HBsAg positivity for more than 6 months,
  • positive or negative serum HBeAg,
  • serum HBV DNA more than 2,000 IU/mL,
  • highest serum ALT > 1 fold of ULN, but < 2 X ULN on at least two occasions (≧ 3 months apart) in the preceding one year,

Exclusion Criteria:

  • co-infection with HIV, HCV, or HDV,
  • previous exposure to HBV antiviral therapy for more than 12 weeks,
  • presence of cirrhosis on histopathology,
  • hepatic decompensation defined as serum bilirubin > 2mg/dl and prolonged prothrombin time > 3 seconds,
  • concurrent malignant diseases including hepatocellular carcinoma,
  • severe co-morbidity with life expectancy < 1year,
  • pregnant or lactating women,
  • organ transplantation except cornea or hair transplant,
  • suspected or confirmed chronic liver diseases from etiologies other than HBV (e.g. alcoholic hepatitis, Wilson disease, Hemochromatosis…etc),
  • serum creatinine >1.5mg/dL
  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: NCT01522625

Contacts
Contact: Jaw-Town Lin, MD,PhD. 886-2-23123456 ext 62246 jawtown@ntu.edu.tw
Contact: Yao-Chun Hsu, MD, MSc 886-7-6150011 ext 2980 gatsbyhsu@yahoo.com.tw

Locations
Taiwan
Chia-Yi Christine Hospital Recruiting
Chia-Yi, Taiwan, 539
Contact: Chi-Yi Chen, MD    886-5-2765041    01290@cych.org.tw   
E-Da Hospital Recruiting
Kaohsiung, Taiwan, 824
Contact: Yao-Chun Hsu, MD, MSc    886-7-6150011 ext 2980    gatsbyhsu@yahoo.com.tw   
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan, 407
Contact: Chun-Ying Wu, MD, PhD    886-4-23592525    dr.taiwan@yahoo.com.tw   
Chi Mei Medical Center, Liouying Active, not recruiting
Tainan, Taiwan
Mackay Memorial Hosp Not yet recruiting
Taipei, Taiwan, 104
Contact: Wen-Hsiung Chang, MD    02-2543-3535    d220533864@yahoo.com.tw   
National Taiwan University Hospital Yun-Lin Branch Recruiting
Yunlin County, Taiwan, 640
Contact: Chieh-Chang Chen, MD       chiehchang.chen@gmail.com   
Principal Investigator: Chieh-Chang Chen, MD         
Sponsors and Collaborators
E-DA Hospital
Gilead Sciences
Taipei Institute of Pathology, Taiwan
Investigators
Principal Investigator: Yao-Chun Hsu, MD, MSc E-Da Hospital, Kaohsiung, Taiwan
Study Chair: Jaw-Town Lin, MD, PhD National Taiwan University
  More Information

No publications provided

Responsible Party: Hung Chi Chen, superintendent, E-DA Hospital
ClinicalTrials.gov Identifier: NCT01522625     History of Changes
Other Study ID Numbers: EMRP36100N
Study First Received: January 27, 2012
Last Updated: October 14, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by E-DA Hospital:
chronic hepatitis B
hepatitis B viral DNA
antiviral therapy
Tenofovir

Additional relevant MeSH terms:
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis A
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 18, 2014