Tenofovir in Chronic Hepatitis B With Mild ALT Elevation

Chronic Hepatitis B Clinical Trial

Official title:

Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients With High Viral Load But Slight Aminotransferase Elevation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01522625
• Other study ID #: EMRP36100N
• Status: Completed
• Phase: Phase 4
• Start date: January 2012
• Est. completion date: December 2018

Study information

• Verified date: February 2019
• Source: E-DA Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: December 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• tenofovir disoproxil fumarate 300mg per day
tenofovir disoproxil fumarate 300mg per day for 3 years
• Placebo
Placebo, identical to TDF in appearance, once daily for 3years

Locations

Country	Name	City	State
Taiwan	Chia-Yi Christine Hospital	Chiayi City
Taiwan	E-Da Hospital	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi Mei Medical Center, Liouying	Tainan
Taiwan	Mackay Memorial Hosp	Taipei
Taiwan	National Taiwan University Hospital Yun-Lin Branch	Yunlin

Sponsors (3)

Lead Sponsor	Collaborator
E-DA Hospital	Gilead Sciences, Taipei Institute of Pathology

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Within one month after completion of antiviral therapy
Secondary	Undetectable hepatitis B viral DNA	HBV DNA viral DNA not detected in serum	Within one month after completion of antiviral therapy
Secondary	Normalization of serum alanine aminotransferase	serum ALT <40 IU/mL	Within one month after completion of antiviral therapy
Secondary	Serum level of HBsAg	quantification of serum HBV serface antigen	Within one month after completion of antiviral therapy
Secondary	Serious adverse reaction	Defined as death, life threatening event, permanent or temporary disability, and hospitalization	Within one month after completion of antiviral therapy