Tenofovir in Chronic Hepatitis B With Mild ALT Elevation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01522625
Recruitment Status : Active, not recruiting
First Posted : January 31, 2012
Last Update Posted : March 21, 2017
Gilead Sciences
Taipei Institute of Pathology
Information provided by (Responsible Party):
Tu, Yuan-Kun, E-DA Hospital

Brief Summary:
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 or disease Intervention/treatment Phase
Chronic Hepatitis B Drug: tenofovir disoproxil fumarate 300mg per day Drug: Placebo Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients With High Viral Load But Slight Aminotransferase Elevation
Study Start Date : January 2012
Estimated Primary Completion Date : January 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Severity of hepatic necroinflammation and fibrosis [ Time Frame: Within one month after completion of antiviral therapy ]
    Primary outcome is the severity of necroinflammation and fibrosis in liver tissue as evaluated by Knodell and Ishak scoring system

Secondary Outcome Measures :
  1. Undetectable hepatitis B viral DNA [ Time Frame: Within one month after completion of antiviral therapy ]
    HBV DNA viral DNA not detected in serum

  2. Normalization of serum alanine aminotransferase [ Time Frame: Within one month after completion of antiviral therapy ]
    serum ALT <40 IU/mL

  3. Serum level of HBsAg [ Time Frame: Within one month after completion of antiviral therapy ]
    quantification of serum HBV serface antigen

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

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Ages Eligible for Study:   25 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01522625

Chia-Yi Christine Hospital
Chia-Yi, Taiwan, 539
E-Da Hospital
Kaohsiung, Taiwan, 824
Taichung Veterans General Hospital
Taichung, Taiwan, 407
Chi Mei Medical Center, Liouying
Tainan, Taiwan
Mackay Memorial Hosp
Taipei, Taiwan, 104
National Taiwan University Hospital Yun-Lin Branch
Yunlin County, Taiwan, 640
Sponsors and Collaborators
E-DA Hospital
Gilead Sciences
Taipei Institute of Pathology
Principal Investigator: Yao-Chun Hsu, MD, MSc E-Da Hospital, Kaohsiung, Taiwan
Study Chair: Jaw-Town Lin, MD, PhD National Taiwan University

Responsible Party: Tu, Yuan-Kun, superintendent, E-DA Hospital Identifier: NCT01522625     History of Changes
Other Study ID Numbers: EMRP36100N
First Posted: January 31, 2012    Key Record Dates
Last Update Posted: March 21, 2017
Last Verified: March 2017

Keywords provided by Tu, Yuan-Kun, E-DA Hospital:
chronic hepatitis B
hepatitis B viral DNA
antiviral therapy

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