Comparisons of efficacy and safety between Tenofovir and Entecavir drugs in chronic hepatitis B patients
| ISRCTN | ISRCTN18291875 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18291875 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | 100-06070D |
| Sponsor | Kaohsiung Chang Gung Memorial Hospital |
| Funder | Investigator initiated and funded |
- Submission date
- 25/08/2019
- Registration date
- 03/09/2019
- Last edited
- 06/09/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
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
Contact information
Scientific
123 Ta-Pei Road
Niao Sung District
Kaohsiung
833
Taiwan
 ORCID ID |
0000-0002-9172-1967 |
|---|---|
| Phone | +886-7-7317123 Ext. 8301 |
| dr.hu@msa.hinet.net |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Open level randomized control trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | Comparisons of efficacy and safety between Tenofovir and Entecavir in chronic hepatitis B patients: an open level randomized clinical trial |
| Study objectives | Tenofovir and Entecavir have similar antiviral efficacy but Tenofovir has an adverse effect on renal and function and bone density |
| Ethics approval(s) | 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 |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Tenofovir disoproxil fumarate, Entecavir |
| Primary outcome measure(s) |
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 |
| Key secondary outcome measure(s) |
1. Presence of HBsAg, HBeAg was assessed using electrochemiluinesence immunoassay (ECLIA) 3.0 |
| Completion date | 03/08/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 288 |
| Key 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. |
| Key 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) |
| Date of first enrolment | 01/04/2012 |
| Date of final enrolment | 31/07/2016 |
Locations
Countries of recruitment
- Taiwan
Study participating centre
Niao Sung District
Kaohsiung
833
Taiwan
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Other |
| IPD sharing plan | All data generated or analysed during this study will be included in the subsequent results publication |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
06/09/2019: Internal review.
03/09/2019: Trial’s existence confirmed by Ethics Committee of Chang Gung Memorial Hospital
