Chronic Hepatitis BPhase 4NCT01522625
Tenofovir in Chronic Hepatitis B With Mild ALT Elevation
A Phase 4 study testing tenofovir disoproxil fumarate 300mg per day in people with Chronic Hepatitis B, run by E-DA Hospital at 6 sites in Taiwan.
Trial summary
This study aims to clarify whether patients with chronic hepatitis B with high viral load will benefit from oral antiviral therapy despite only mildly elevated serum liver enzyme. Read more about this study
- Who is it for?
- Ages 25 to 70 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- tenofovir disoproxil fumarate 300mg per day
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 6 sitesTaiwan
- Study dates
- Jan 2012to Dec 2018
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age between 25 to 70 years,
- serum HBsAg positivity for more than 6 months,
- positive or negative serum HBeAg,
- serum HBV DNA more than 2,000 IU/mL,
- highest serum ALT > 1 fold of ULN, but < 2 X ULN on at least two occasions (≧ 3 months apart) in the preceding one year,
Who cannot join
- co-infection with HIV, HCV, or HDV,
- previous exposure to HBV antiviral therapy for more than 12 weeks,
- presence of cirrhosis on histopathology,
- hepatic decompensation defined as serum bilirubin > 2mg/dl and prolonged prothrombin time > 3 seconds,
- concurrent malignant diseases including hepatocellular carcinoma,
- severe co-morbidity with life expectancy < 1year,
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- pregnant or lactating women,
- organ transplantation except cornea or hair transplant,
- suspected or confirmed chronic liver diseases from etiologies other than HBV (e.g. alcoholic hepatitis, Wilson disease, Hemochromatosis…etc),
- serum creatinine >1.5mg/dL
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Taiwan6 sites
Chia-Yi Christine Hospital
Chiayi City, 539
E-Da Hospital
Kaohsiung City, 824
Taichung Veterans General Hospital
Taichung, 407
Chi Mei Medical Center, Liouying
Tainan
Mackay Memorial Hosp
Taipei, 104
National Taiwan University Hospital Yun-Lin Branch
Yunlin, 640
About this study
Official title: Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients With High Viral Load But Slight Aminotransferase Elevation
This study aims to clarify whether patients with chronic hepatitis B with high viral load will benefit from oral antiviral therapy despite only mildly elevated serum liver enzyme.
Read the detailed description
Chronic hepatitis B (CHB) is a serious disease in Taiwan, leading to substantial morbidity and mortality including hepatic failure, liver cirrhosis, and hepatocellular carcinoma (HCC). Recently a large body of evidence supports that high level of serum HBV DNA is an independent risk factor for late complications in CHB patients. Nucleos(t)ide analogues (NUC) are effective antiviral therapy that can potently inhibit replication of hepatitis B virus (HBV), and has been widely used in management of patients with CHB. Current practice guidelines recommend using serum alanine aminotransferase (ALT) > 2 times of the upper limit of normal (ULN) as the prerequisite to initiate antiviral therapy in compensated CHB patients without liver cirrhosis. However, serum ALT level does not exactly correlate with serum HBV DNA or liver tissue injury. Whether antiviral therapy improves outcomes of patients with slightly elevated ALT (i.e. 1-2 folds of ULN) remains unknown.
- Conditions
- Chronic Hepatitis B
- Being tested
- tenofovir disoproxil fumarate 300mg per day, Placebo
- Keywords
- chronic hepatitis B, hepatitis B viral DNA, antiviral therapy, Tenofovir
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tenofovir disoproxil fumarate 300mg per dayDrug
Also called Viread® (Gilead Sciences Inc)
tenofovir disoproxil fumarate 300mg per day for 3 years
PlaceboDrug
Placebo, identical to TDF in appearance, once daily for 3years
| Study group | Role | What they receive |
|---|---|---|
| TDF | Experimental | tenofovir disoproxil fumarate (TDF) 300mg Receives: Drug: tenofovir disoproxil fumarate 300mg per day |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of hepatic necroinflammation and fibrosis
Primary outcome is the severity of necroinflammation and fibrosis in liver tissue as evaluated by Knodell and Ishak scoring system
Measured: Within one month after completion of antiviral therapy
Secondary outcomes (4)
Undetectable hepatitis B viral DNA
HBV DNA viral DNA not detected in serum
Measured: Within one month after completion of antiviral therapy
Normalization of serum alanine aminotransferase
serum ALT <40 IU/mL
Measured: Within one month after completion of antiviral therapy
Serum level of HBsAg
quantification of serum HBV serface antigen
Measured: Within one month after completion of antiviral therapy
Serious adverse reaction
Defined as death, life threatening event, permanent or temporary disability, and hospitalization
Measured: Within one month after completion of antiviral therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionNov 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- E-DA Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Gilead Sciences, Taipei Institute of Pathology
- Responsible party
- Principal investigator, Tu, Yuan-Kun, E-DA Hospital
- Investigators
- Yao-Chun Hsu, MD, MSc, Principal investigator, E-Da Hospital, Kaohsiung, TaiwanJaw-Town Lin, MD, PhD, Study chair, National Taiwan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01522625
- Sponsor's protocol ID
- EMRP36100N
- Status last verified
- Feb 2019
- First submitted
- 27 Jan 2012
- Last updated
- 12 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Hsu YC, Chen CY, Chang IW, Chang CY, Wu CY, Lee TY, Wu MS, Bair MJ, Chen JJ, Chen CC, Tseng CH, Tai CM, Huang YT, Ku WH, Mo LR, Lin JT. Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial. Lancet Infect Dis. 2021 Jun;21(6):823-833. doi: 10.1016/S1473-3099(20)30692-7. Epub 2021 Jan 29.
PubMed 33524314
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients With High Viral Load But Slight Aminotransferase Elevation
- ClinicalTrials.gov ID
- NCT01522625
- Acronym / sponsor ID
- EMRP36100N
- Conditions
- Chronic Hepatitis B
- Keywords
- chronic hepatitis B, hepatitis B viral DNA, antiviral therapy, Tenofovir
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- E-DA HospitalUniversity, hospital or other
- Collaborators
- Gilead Sciences, Taipei Institute of Pathology
- Study start
- Jan 2012
- Primary completion
- Nov 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 31 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to clarify whether patients with chronic hepatitis B with high viral load will benefit from oral antiviral therapy despite only mildly elevated serum liver enzyme.
Detailed description
Chronic hepatitis B (CHB) is a serious disease in Taiwan, leading to substantial morbidity and mortality including hepatic failure, liver cirrhosis, and hepatocellular carcinoma (HCC). Recently a large body of evidence supports that high level of serum HBV DNA is an independent risk factor for late complications in CHB patients. Nucleos(t)ide analogues (NUC) are effective antiviral therapy that can potently inhibit replication of hepatitis B virus (HBV), and has been widely used in management of patients with CHB. Current practice guidelines recommend using serum alanine aminotransferase (ALT) > 2 times of the upper limit of normal (ULN) as the prerequisite to initiate antiviral therapy in compensated CHB patients without liver cirrhosis. However, serum ALT level does not exactly correlate with serum HBV DNA or liver tissue injury. Whether antiviral therapy improves outcomes of patients with slightly elevated ALT (i.e. 1-2 folds of ULN) remains unknown.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TDF | Experimental | Drug: tenofovir disoproxil fumarate 300mg per daytenofovir disoproxil fumarate (TDF) 300mg |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 25 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- age between 25 to 70 years,
- serum HBsAg positivity for more than 6 months,
- positive or negative serum HBeAg,
- serum HBV DNA more than 2,000 IU/mL,
- highest serum ALT > 1 fold of ULN, but < 2 X ULN on at least two occasions (≧ 3 months apart) in the preceding one year,
Key exclusion criteria (10 listed)
- co-infection with HIV, HCV, or HDV,
- previous exposure to HBV antiviral therapy for more than 12 weeks,
- presence of cirrhosis on histopathology,
- hepatic decompensation defined as serum bilirubin > 2mg/dl and prolonged prothrombin time > 3 seconds,
- concurrent malignant diseases including hepatocellular carcinoma,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| tenofovir disoproxil fumarate 300mg per dayAlso: Viread® (Gilead Sciences Inc)tenofovir disoproxil fumarate 300mg per day for 3 years | Drug | TDF |
| PlaceboPlacebo, identical to TDF in appearance, once daily for 3years | Drug | Placebo |
Primary outcome
Severity of hepatic necroinflammation and fibrosis
Time frame: Within one month after completion of antiviral therapy
Primary outcome is the severity of necroinflammation and fibrosis in liver tissue as evaluated by Knodell and Ishak scoring system
4 secondary outcomes
Undetectable hepatitis B viral DNA
Time frame: Within one month after completion of antiviral therapy
Normalization of serum alanine aminotransferase
Time frame: Within one month after completion of antiviral therapy
Serum level of HBsAg
Time frame: Within one month after completion of antiviral therapy
Serious adverse reaction
Time frame: Within one month after completion of antiviral therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2019.
- Derived from this study: PubMed 33524314Hsu YC, Chen CY, Chang IW, Chang CY, Wu CY, Lee TY, Wu MS, Bair MJ, Chen JJ, Chen CC, Tseng CH, Tai CM, Huang YT, Ku WH, Mo LR, Lin JT. Once-daily tenofovir disoproxil fumarate in treatment-naive Taiwanese patients with chronic hepatitis B and minimally raised alanine aminotransferase (TORCH-B): a multicentre, double-blind, placebo-controlled, parallel-group, randomised trial. Lancet Infect Dis. 2021 Jun;21(6):823-833. doi: 10.1016/S1473-3099(20)30692-7. Epub 2021 Jan 29.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yao-Chun Hsu, MD, MSc principal investigator
E-Da Hospital, Kaohsiung, Taiwan
Jaw-Town Lin, MD, PhD study chair
National Taiwan University
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing tenofovir disoproxil fumarate 300mg per day in people with Chronic Hepatitis B, run by E-DA Hospital at 6 sites in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Severity of hepatic necroinflammation and fibrosis (time frame: Within one month after completion of antiviral therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01522625, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2019.