Use of TDF in Patients With Inactive Chronic Hepatitis B Infection

NCT ID: NCT02600117

Last Updated: 2023-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-26
• Study Completion Date: 2023-02-28

Brief Summary

Recent evidence suggests that patients with inactive chronic hepatitis B (CHB) may develop the same types of liver complications that patients in the active state of hepatitis B virus (HBV) infection experience. Treatment guidelines for patients in the active state of HBV infection indicate that HBsAg clearance is associated with definitive remission of the activity of chronic HBV & improved long-term outcome. Clinical data showed that HBsAg clearance is achievable, in a small population of patients on continuous treatment with potent oral antivirals (OAVs), such as tenofovir disoproxil fumarate (TDF). It is possible the same OAVs can have the same effect in patients with inactive CHB, but in a shorter treatment duration. The purpose of this study is to find out if TDF is effective in controlling HBV DNA & promoting seroconversion from HBsAg-positive to HBsAb-positive in patients with inactive CHB.

Detailed Description

Hepatitis B virus (HBV) infection is a major worldwide health problem. The course of the majority of patients with inactive chronic hepatitis B is usually benign; therefore, the current treatment guidelines recommend not treating these patients. However, recent evidence suggests that the prognosis of these inactive carrier is not exactly benign. For instance, patients may develop liver cancer despite their inactive carrier state. Also, approximately 20-30% of patients with inactive chronic hepatitis B may undergo spontaneous reactivation of hepatitis over time. Multiple episodes of reactivation or sustained reactivation can cause progressive liver damage and even liver decompensation. However, until there are data to support that treatment with oral antivirals can alter the outcome of these patients, they will remain untreated. Potent oral antivirals have been shown to suppress HBV DNA and normalize liver enzymes in patients with active chronic hepatitis B infection. With continued long-term treatment, some of these patients have gone on to clear hepatitis B surface antigen and develop hepatitis B surface antibody. Therefore, it is possible that the same oral antivirals can have the same effect in patients with inactive chronic hepatitis B, but in a shorter duration of treatment. This study will explore the possible use of tenofovir disoproxil fumarate in controlling HBV DNA and promoting hepatitis B surface antigen seroconversion in patients with inactive chronic hepatitis B.

After completion of all initial investigations, patients will be started on TDF 300mg daily. Patients will be reviewed at 6 monthly intervals as per standard of care. At each clinic visit, patients will have blood tests including complete blood count, renal function, electrolytes, liver enzyme and liver function tests, as well as HBV serology including quantitative HBsAg and HBV DNA. Patients will also receive an abdominal ultrasound, fibroscan and fibrotest on an annual basis. Treatment will be stopped when sAg+ve seroconverts to sAb+ve or at the end of 3 years whichever comes earlier.

Conditions

Hepatitis B, Chronic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tenofovir disoproxil fumarate

300 mg, orally, once a day for 3 years or when sAg+ve seroconverts to sAb+ve whichever comes earlier

Group Type: OTHER

Tenofovir disoproxil fumarate

Intervention Type: DRUG

300 mg, oral, once a day

Interventions

Tenofovir disoproxil fumarate

300 mg, oral, once a day

Intervention Type: DRUG

Other Intervention Names

Viread

Eligibility Criteria

Inclusion Criteria

• All patients with inactive chronic hepatitis B, defined as someone who has HBV DNA ≤ log4, eAg-ve, eAb+, HBsAg+ve and normal ALT persistently for >6 months

Exclusion Criteria

• Patients older than 75 years of age
• Presence of hepatoma at entry
• Presence of decompensated cirrhosis defined by a history of variceal bleed, ascites, or hepatic encephalopathy
• Presence of abnormal renal function defined as serum creatinine of>110µmol/L
• co-infection with HIV

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Florence Wong

MD, Hepatologist, Professor-Division of Gastroenterology,Department of Medicine, University of Toronto

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Florence Wong, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network -Toronto General Hospital

Locations

University Health Network - Toronto General Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

IN-CA-174-1708

Identifier Type: OTHER

Identifier Source: secondary_id

15-8950

Identifier Type: -

Identifier Source: org_study_id