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Tenofovir in Chronic Hepatitis B With Mild ALT Elevation

Primary Purpose

Chronic Hepatitis B

Status
Completed
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
tenofovir disoproxil fumarate 300mg per day
Placebo
Sponsored by
E-DA Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B focused on measuring chronic hepatitis B, hepatitis B viral DNA, antiviral therapy, Tenofovir

Eligibility Criteria

25 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Chia-Yi Christine Hospital
  • E-Da Hospital
  • Taichung Veterans General Hospital
  • Chi Mei Medical Center, Liouying
  • Mackay Memorial Hosp
  • National Taiwan University Hospital Yun-Lin Branch

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

TDF

Placebo

Arm Description

tenofovir disoproxil fumarate (TDF) 300mg

Outcomes

Primary Outcome Measures

Severity of hepatic necroinflammation and fibrosis
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
HBV DNA viral DNA not detected in serum
Normalization of serum alanine aminotransferase
serum ALT <40 IU/mL
Serum level of HBsAg
quantification of serum HBV serface antigen
Serious adverse reaction
Defined as death, life threatening event, permanent or temporary disability, and hospitalization

Full Information

First Posted
January 27, 2012
Last Updated
February 10, 2019
Sponsor
E-DA Hospital
Collaborators
Gilead Sciences, Taipei Institute of Pathology
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1. Study Identification

Unique Protocol Identification Number
NCT01522625
Brief Title
Tenofovir in Chronic Hepatitis B With Mild ALT Elevation
Official Title
Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients With High Viral Load But Slight Aminotransferase Elevation
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
E-DA Hospital
Collaborators
Gilead Sciences, Taipei Institute of Pathology

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
chronic hepatitis B, hepatitis B viral DNA, antiviral therapy, Tenofovir

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
160 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TDF
Arm Type
Experimental
Arm Description
tenofovir disoproxil fumarate (TDF) 300mg
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
tenofovir disoproxil fumarate 300mg per day
Other Intervention Name(s)
Viread® (Gilead Sciences Inc)
Intervention Description
tenofovir disoproxil fumarate 300mg per day for 3 years
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo, identical to TDF in appearance, once daily for 3years
Primary Outcome Measure Information:
Title
Severity of hepatic necroinflammation and fibrosis
Description
Primary outcome is the severity of necroinflammation and fibrosis in liver tissue as evaluated by Knodell and Ishak scoring system
Time Frame
Within one month after completion of antiviral therapy
Secondary Outcome Measure Information:
Title
Undetectable hepatitis B viral DNA
Description
HBV DNA viral DNA not detected in serum
Time Frame
Within one month after completion of antiviral therapy
Title
Normalization of serum alanine aminotransferase
Description
serum ALT <40 IU/mL
Time Frame
Within one month after completion of antiviral therapy
Title
Serum level of HBsAg
Description
quantification of serum HBV serface antigen
Time Frame
Within one month after completion of antiviral therapy
Title
Serious adverse reaction
Description
Defined as death, life threatening event, permanent or temporary disability, and hospitalization
Time Frame
Within one month after completion of antiviral therapy

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Yao-Chun Hsu, MD, MSc
Organizational Affiliation
E-Da Hospital, Kaohsiung, Taiwan
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jaw-Town Lin, MD, PhD
Organizational Affiliation
National Taiwan University
Official's Role
Study Chair
Facility Information:
Facility Name
Chia-Yi Christine Hospital
City
Chiayi City
ZIP/Postal Code
539
Country
Taiwan
Facility Name
E-Da Hospital
City
Kaohsiung
ZIP/Postal Code
824
Country
Taiwan
Facility Name
Taichung Veterans General Hospital
City
Taichung
ZIP/Postal Code
407
Country
Taiwan
Facility Name
Chi Mei Medical Center, Liouying
City
Tainan
Country
Taiwan
Facility Name
Mackay Memorial Hosp
City
Taipei
ZIP/Postal Code
104
Country
Taiwan
Facility Name
National Taiwan University Hospital Yun-Lin Branch
City
Yunlin
ZIP/Postal Code
640
Country
Taiwan

12. IPD Sharing Statement

Citations:
PubMed Identifier
33524314
Citation
Hsu YC, Chen CY, Chang IW, Chang CY, Wu CY, Lee TY, Wu MS, Bair MJ, Chen JJ, Chen CC, Tseng CH, Tai CM, Huang YT, Ku WH, Mo LR, Lin JT. Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial. Lancet Infect Dis. 2021 Jun;21(6):823-833. doi: 10.1016/S1473-3099(20)30692-7. Epub 2021 Jan 29. Erratum In: Lancet Infect Dis. 2021 May;21(5):e122.
Results Reference
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Tenofovir in Chronic Hepatitis B With Mild ALT Elevation

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