Comparisons of efficacy and safety between Tenofovir and Entecavir drugs in chronic hepatitis B patients

ISRCTN ISRCTN18291875
DOI https://doi.org/10.1186/ISRCTN18291875
Secondary identifying numbers 100-06070D
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
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

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

Mr Tsung-Hui Hu
Scientific

123 Ta-Pei Road
Niao Sung District
Kaohsiung
833
Taiwan

ORCiD logoORCID ID 0000-0002-9172-1967
Phone +886-7-7317123 Ext. 8301
Email dr.hu@msa.hinet.net

Study information

Study designOpen level randomized control trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleComparisons of efficacy and safety between Tenofovir and Entecavir in chronic hepatitis B patients: an open level randomized clinical trial
Study objectivesTenofovir 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) studiedHepatitis B
InterventionThis 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Tenofovir disoproxil fumarate, Entecavir
Primary outcome measureProportion 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 measures1. 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 study start date01/04/2012
Completion date03/08/2018

Eligibility

Participant type(s)Patient
Age groupAdult
SexBoth
Target number of participants144 HBeAg postive patient; 144 HBeAg negative patient
Key inclusion criteriaThe 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 criteria1. 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 enrolment01/04/2012
Date of final enrolment31/07/2016

Locations

Countries of recruitment

  • Taiwan

Study participating centre

Kaohsiung Chang Gung Memorial Hospital
123 Ta-Pei Road
Niao Sung District
Kaohsiung
833
Taiwan

Sponsor information

Kaohsiung Chang Gung Memorial Hospital
Hospital/treatment centre

123 Ta-Pei Road
Niao Sung District
Kaohsiung
833
Taiwan

Phone +886-7-7317123
Email dr.hu@msa.hinet.net
Website https://www1.cgmh.org.tw/branch/shk/index.htm
ROR logo "ROR" https://ror.org/00k194y12

Funders

Funder type

Other

Investigator initiated and funded

No information available

Results and Publications

Intention to publish date30/10/2019
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryOther
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal
IPD sharing planAll data generated or analysed during this study will be included in the subsequent results publication

Editorial Notes

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