Plain English Summary
Background and study aims
Hepatitis B virus (HBV) infection is an important global health problem with an estimated 400 million chronically infected people. Patients with chronic hepatitis B (CHB) have a lifetime risk of 15-40% to develop liver cirrhosis and hepatocellular carcinoma (HCC). Increasing HBV DNA levels have also been shown to be associated with increasing risk of liver cirrhosis and HCC. Thus, one of the primary objectives of anti-HBV therapy is complete sustained suppression of viral replication to prevent HBV related cirrhosis, HCC and even mortality. Entecavir (ETV) and
Tenofovir (TDF) are two potent drugs to suppress viral replication with lower rate or absence of long-term resistance in clinical trials and real-word experience. ETV and TDF are recommended as first line antiviral agents in CHB treatment.
Who can participate?
Patients with CHB and NA-naïve HBeAg-positive or HBeAg-negative over age 20 who meet the national reimbursement criteria in Taiwan.
What does the study involve?
Participants are randomized 1:1 to receive ETV 0.5mg or TDF 300mg once daily for 144 weeks. All patients were followed up at week 4 and 12 and then every 12 weeks after.
What are the possible benefits and risk of participating?
Participants may benefit from Tenofovir or Entercavir treatment in patients with chronic active hepatitis or cirrhosis.
Possible risks may be mild decrease eGFR and bone density changes.
Where is the study run from?
Kaohsiung Chang Gung Memorial Hospital, Taiwan
When is the study starting and how long is it expected to run for?
April 2012 to July 2018
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Dr Tsung-Hui Hu
dr.hu@msa.hinet.net
Trial website
Contact information
Type
Scientific
Primary contact
Mr Tsung-Hui Hu
ORCID ID
http://orcid.org/0000-0002-9172-1967
Contact details
123 Ta-Pei Road
Niao Sung District
Kaohsiung
833
Taiwan
+886-7-7317123 Ext. 8301
dr.hu@msa.hinet.net
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
100-06070D
Study information
Scientific title
Comparisons of efficacy and safety between Tenofovir and Entecavir in chronic hepatitis B patients: an open level randomized clinical trial
Acronym
Study hypothesis
Tenofovir and Entecavir have similar antiviral efficacy but Tenofovir has an adverse effect on renal and function and bone density
Ethics approval
Approved 30/04/2012, Ethics Committee of Chang Gung Memorial Hospital (No 199, Dunhua N Rd. Songshan Dist. Taipei City, Taiwan; ccyi@cgmh.org.tw; +886-3-3196200 ext 3713), ref: 100-06070D
Study design
Open level randomized control trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Hepatitis B
Intervention
This was a randomized, open-label study in NA-naïve HBeAg-positive and HBeAg-negative patients with CHB.
Each patient was randomized 1:1 to receive ETV 0.5mg or TDF 300mg once daily for 144 weeks. Randomized treatment assignments were generated by a central randomization center. Patients were randomized using a block design stratified by gender, HBeAg status, HBV-DNA levels and cirrhosis status.
All patients were followed up at week 4 and 12 and then every 12 weeks after.
Intervention type
Drug
Phase
Not Applicable
Drug names
Tenofovir disoproxil fumarate, Entecavir
Primary outcome measure
Proportion of patients with undetectable HBV DNA level at week 48, 96 and 144. Serum HBV DNA levels were analyzed using the Cobas AmpliPrep-Cobas TaqMan HBV test (CAP-CTM)(Roche Molecular System, Inc., Branchburg, NJ, USA), with a lower detection limit of 70 copies/ml
Secondary outcome measures
1. Presence of HBsAg, HBeAg was assessed using electrochemiluinesence immunoassay (ECLIA) 3.0
2. Renal function measured by the serum creatinine and estimated glomerular filtration rate (eGFR)
3. Anti-HDV antibodies was assessed using radioimmunoassay (Abbott, North Chicago, IL, USA)
Overall trial start date
01/04/2012
Overall trial end date
03/08/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
The inclusion criteria included three populations:
1. Chronic hepatitis B patients with hepatitis B virus surface antigen (HBsAg)
1.1 Positive status for more than 6 months
1.2 Elevated alanine transferase (ALT) levels ≥ 5x ULN (200 IU/L) or ALT levels between 2x and 5x ULN combined HBV DNA ≥20000 IU/ml for HBeAg positive patients
1.2 ALT levels over 2x ULN combined HBV DNA ≥2000 IU/ml for HBeAg negative patients
2. Acute hepatic decompensated patient (prolong prothrombin time >3 sec and bilirubin>2 mg/dL) with positive for HBsAg
3. Clinical cirrhosis with HBV DNA ≥2000 IU/ml. The clinical evidence of cirrhosis was defined by one of the following
3.1 Ultrasound diagnosed liver cirrhosis with evidence of splenomegaly or esophageal or cardiac varices
3.2 Liver biopsy diagnosed liver cirrhosis
4. Aged 20 years or older.
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
144 HBeAg postive patient; 144 HBeAg negative patient
Participant exclusion criteria
1. Patients who had co-infection with human immunodeficiency virus, hepatitis C virus, hepatitis D virus or hepatitis E virus by serological assays
2. Patients who had a significant intake of alcohol (>20g/day for women; 30 g/day for men)
Recruitment start date
01/04/2012
Recruitment end date
31/07/2016
Locations
Countries of recruitment
Taiwan
Trial participating centre
Kaohsiung Chang Gung Memorial Hospital
123 Ta-Pei Road
Niao Sung District
Kaohsiung
833
Taiwan
Sponsor information
Organisation
Kaohsiung Chang Gung Memorial Hospital
Sponsor details
123 Ta-Pei Road
Niao Sung District
Kaohsiung
833
Taiwan
+886-7-7317123
dr.hu@msa.hinet.net
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Other
Funder name
Investigator initiated and funded
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal
IPD sharing statement:
All data generated or analysed during this study will be included in the subsequent results publication
Intention to publish date
30/10/2019
Participant level data
Other
Basic results (scientific)
Publication list