Condition category
Infections and Infestations
Date applied
25/08/2019
Date assigned
03/09/2019
Last edited
06/09/2019
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

https://www1.cgmh.org.tw/branch/shk/index.htm

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

Publication citations

Additional files

Editorial Notes

06/09/2019: Internal review. 03/09/2019: Trial’s existence confirmed by Ethics Committee of Chang Gung Memorial Hospital