Hepatitis BNCT03640728
The Efficacy and Safety of Nucleos(t)Ide Analogues in the Treatment of HBV-related Acute-on-chronic Liver Failure
An observational study of Hepatitis B and Virus Diseases, run by First Affiliated Hospital Xi'an Jiaotong University at 11 sites in China.
Trial summary
HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatitis B, Virus Diseases, Liver Failure
- What is being tested?
- Tenofovir Alafenamide, Entecavir and Tenofovir disoproxil fumarate
- Type of treatment
- Pill or oral medicine
- How many people
- 200 participants
- Where
- 11 sitesChina
- Study dates
- 25 Jan 2019to Jul 2023
- Phase
- Observational
- 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 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All the patients received antivirals will be followed for at least 48 weeks and follow-up assessments were performed at week 1, 2, 3, 4, 12, 24 and 48.All the patients were detected Serum HBV DNA,HBV markers, including HBsAg, HBsAb, HBeAg, HBeAb and HBcAb, routine biochemical tests mainly including ALT,AST,TB and ALB.
Who may be able to join
- age 18-70 years, male or female.
- HBsAg positive at least 6 months or more, HBeAg positive or negative.
- Serum HBV DNA positive (Serum HBV DNA should be determined by the PCR assay at the local laboratory at screening for this study)
- Recent development of increasing jaundice (a total serum bilirubin concentration of above 85μmol/L) and coagulopathy (INR ≥1.5 or prothrombin activity<40%)
- Recent development of complications such as hepatic encephalopathy, or abrupt and obvious increase in ascites, or spontaneous bacterial peritonitis, or hepatorenal syndrome.
- Patient is willing and able to comply with the study drug regimen and all other study requirements.
- The patient is willing and able to provide written informed consent to participate in the study.
Who cannot join
- Patient has concomitant other chronic viral infection (HCV or HIV)
- Patient has evidence of renal insufficiency defined as serum creatinine > 1.5 mg/dL
- Patient has medical condition that requires concurrent use of systemic prednisolone or other immunosuppressive agent (including chemotherapeutic agent)
- Patient is pregnant or breastfeeding or willing to be pregnant
- Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease, etc.).
- A history of treated malignancy (other than hepatocellular carcinoma) is allowable if the patient's malignancy has been in complete remission, off chemotherapy and without additional surgical intervention, during the preceding three years.
- Active ethanol/drug abuse/psychiatric problems such as major depression, schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety, personality disorder that might interfere with participation in the study.
- Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
China11 sites, 10 recruiting
- Recruiting
Ankang Central Hospital
Ankang
- Not yet recruiting
Hanzhong 3201 Hospital
Hanzhong
- Not yet recruiting
Hanzhong Infectious Hospital
Hanzhong
- Not yet recruiting
Weinan Central Hospital
Weinan
- Recruiting
First Affiliated Hospital Xi'an Jiaotong University
Xi'an
- Not yet recruiting
Shaanxi provincial people's hospital
Xi'an
- Not yet recruiting
Tangdu Hospital, The Fourth Military Medical University,
Xi'an
- Recruiting
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an
- Active, not recruiting
Xi'an Central Hospital
Xi'an
- Not yet recruiting
Xijing Hospital, The Fourth Military Medical University
Xi'an
- Not yet recruiting
The Affiliated Hospital of Yan'an University
Yan’an
About this study
Official title: A Multicenter Controlled Open-label Trial of Evaluating Tenofovir Alafenamide, Tenofovir Disoproxil Fumarate and Entecavir in Acute-on-chronic Liver Failure of Chronic Hepatitis B Patients
HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. However, no conclusion on which nucleoside analogue is the most satisfactory drug for the treatment of HBV-related liver failure has not been reached yet. In this cohort study, the investigators will compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF) and entecavir (ETV) in HBV-related ACLF in China. In addition, the drug metabolism characteristics of TAF will be explored in such severe liver injury population of HBV-ACLF.
Read the detailed description
Potent antivirals like entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF) and Tenofovir alafenamide (TAF) now are recommended as first-line therapy for patients with chronic HBV infection because of their significant suppression of viral replication and a high barrier to resistance. HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Only a limited number of medical treatments are available for ACLF. Although liver transplantation is a life-saving treatment for ACLF, the difficulty in finding a suitable donor and the high cost hinder its extensive clinical use.
The precise mechanism underlying the liver injury caused by HBV-related ACLF and the factors contributing to the progression of liver failure remain unknown. HBV DNA replication is one of the key factors causing the progression from liver damage to liver failure. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. However, the specific antiviral treatment for patients with liver failure remains unclear. In the past years, efficacy of nucleoside analogues, such as lamivudine, entecavir, telbivudine and tenofovir, for HBV-related liver failure has been reported. However, no conclusion on which nucleoside analogue is the most satisfactory drug for the treatment of HBV-related liver failure has not been reached yet.
In this cohort study, the investigators will compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF) and entecavir (ETV) in HBV-related ACLF in China. In addition, pharmacokinetic properties of TAF tablets will be explored in the study subjects.
- Conditions
- Hepatitis B, Virus Diseases, Liver Failure
- Being tested
- Tenofovir Alafenamide, Entecavir, Tenofovir disoproxil fumarate
- Keywords
- Hepatitis B, Acute-on-Chronic liver failure
- Medical subject headings
- Hepatitis B, Virus Diseases, Liver Failure, Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir AlafenamideDrug
Tenofovir alafenamide 25 mg/day orally
EntecavirDrug
Entecavir 0.5 mg/day orally
Tenofovir disoproxil fumarateDrug
Tenofovir Disoproxil Fumarate 300 mg/day orally
| Study group | Role | What they receive |
|---|---|---|
| ETV | patients receive entecavir 0.5 mg/day orally. Receives: Drug: Entecavir | |
| TDF | patients receive Tenofovir Disoproxil Fumarate 300 mg/day orally. Receives: Drug: Tenofovir disoproxil fumarate | |
| TAF | patients receive Tenofovir alafenamide 25 mg/day orally. Receives: Drug: Tenofovir Alafenamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival of ACLF subjects
Overall survival in subjects with acute-on-chronic liver failure will be summarized and compared with control subjects through study day 28 and week 48.
Measured: study day 1 through week 48
Secondary outcomes (7)
Changes in serum HBV DNA levels
Measured: at week 4 and 48 of treatment
Proportion of patients with hepatitis B e-Ag(HBe-Ag) loss or seroconversion
Measured: at week 4 and 48 of treatment
Proportion of patients with HBs-Ag loss or seroconversion
Measured: at week 4 and 48 of treatment
Proportion of patients with normal alanine aminotransferase(ALT)
Measured: at week 4 and 48 of treatment
Liver function evaluation through Model for End-Stage Liver Disease (MELD) scores
Model for End-Stage Liver Disease(MELD) Score is calculated according to the equation:3.78×ln[serum bilirubin (mg/dl)] + 11.2×ln(INR) + 9.57×ln[serum creatinine (mg/dL)] + 6.43. Liver function improvement defined as the decline of total MELD score, whereas liver function deterioration defined as the rise of total MELD score. The risk of death increased when total MELD score above 25.
Measured: at week 4 and 48 of treatment
Proportion of patients with virologic breakthrough
Virologic breakthrough is defined as the increase in serum HBV DNA by >1 log10 (10-fold) above nadir after achieving virologic response as determined by at least 2 consecutive measurements of at least 2 weeks apart, during continued treatment
Measured: at week 4 and 48 of treatment
Proportion of patients with complete virologic response
Virologic response is defined as the serum HBV DNA concentrations below 20 IU/mL
Measured: at week 4 and 48 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2018
- Study start25 Jan 2019
- Primary completion30 Apr 2021
- Study completionJul 2023 (estimated)
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 Hepatitis BStudies of the same condition, open and under way.
- More trials run by First Affiliated Hospital Xi'an Jiaotong UniversityThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, He Yingli, First Affiliated Hospital Xi'an Jiaotong University
- Investigators
- Yingli He, M.D.,Ph.D, Principal investigator, First Affiliated Hospital Xi'an Jiaotong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03640728
- Sponsor's protocol ID
- XJTU1AF2018LSL-002
- Status last verified
- Feb 2023
- First submitted
- 19 Aug 2018
- Last updated
- 9 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Li J, Hu C, Chen Y, Zhang R, Fu S, Zhou M, Gao Z, Fu M, Yan T, Yang Y, Li J, Liu J, Chen T, Zhao Y, He Y. Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B. BMC Infect Dis. 2021 Jun 14;21(1):567. doi: 10.1186/s12879-021-06237-x.
PubMed 34126939
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Controlled Open-label Trial of Evaluating Tenofovir Alafenamide, Tenofovir Disoproxil Fumarate and Entecavir in Acute-on-chronic Liver Failure of Chronic Hepatitis B Patients
- ClinicalTrials.gov ID
- NCT03640728
- Acronym / sponsor ID
- XJTU1AF2018LSL-002
- Conditions
- Hepatitis B, Virus Diseases, Liver Failure
- Keywords
- Hepatitis B, Acute-on-Chronic liver failure
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- First Affiliated Hospital Xi'an Jiaotong UniversityUniversity, hospital or other
- Study start
- 25 Jan 2019 (actual)
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- Jul 2023 (estimated)
- First posted
- 21 Aug 2018 (actual)
- 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.
HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. However, no conclusion on which nucleoside analogue is the most satisfactory drug for the treatment of HBV-related liver failure has not been reached yet. In this cohort study, the investigators will compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF) and entecavir (ETV) in HBV-related ACLF in China. In addition, the drug metabolism characteristics of TAF will be explored in such severe liver injury population of HBV-ACLF.
Detailed description
Potent antivirals like entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF) and Tenofovir alafenamide (TAF) now are recommended as first-line therapy for patients with chronic HBV infection because of their significant suppression of viral replication and a high barrier to resistance. HBV-related acute-on-chronic liver failure (ACLF) is a clinical syndrome defined as acute hepatic insult with diagnosed or undiagnosed chronic liver disease. Only a limited number of medical treatments are available for ACLF. Although liver transplantation is a life-saving treatment for ACLF, the difficulty in finding a suitable donor and the high cost hinder its extensive clinical use.
The precise mechanism underlying the liver injury caused by HBV-related ACLF and the factors contributing to the progression of liver failure remain unknown. HBV DNA replication is one of the key factors causing the progression from liver damage to liver failure. Current clinical guidelines advocate oral antiviral treatment in HBV-related ACLF. However, the specific antiviral treatment for patients with liver failure remains unclear. In the past years, efficacy of nucleoside analogues, such as lamivudine, entecavir, telbivudine and tenofovir, for HBV-related liver failure has been reported. However, no conclusion on which nucleoside analogue is the most satisfactory drug for the treatment of HBV-related liver failure has not been reached yet.
In this cohort study, the investigators will compare the efficacy, safety, and tolerability of tenofovir alafenamide (TAF), Tenofovir Disoproxil Fumarate (TDF) and entecavir (ETV) in HBV-related ACLF in China. In addition, pharmacokinetic properties of TAF tablets will be explored in the study subjects.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ETV | – | Drug: Entecavirpatients receive entecavir 0.5 mg/day orally. |
| TDF | – | Drug: Tenofovir disoproxil fumaratepatients receive Tenofovir Disoproxil Fumarate 300 mg/day orally. |
| TAF | – | Drug: Tenofovir Alafenamidepatients receive Tenofovir alafenamide 25 mg/day orally. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All the patients received antivirals will be followed for at least 48 weeks and follow-up assessments were performed at week 1, 2, 3, 4, 12, 24 and 48.All the patients were detected Serum HBV DNA,HBV markers, including HBsAg, HBsAb, HBeAg, HBeAb and HBcAb, routine biochemical tests mainly including ALT,AST,TB and ALB.
Key inclusion criteria (7 listed)
- age 18-70 years, male or female.
- HBsAg positive at least 6 months or more, HBeAg positive or negative.
- Serum HBV DNA positive (Serum HBV DNA should be determined by the PCR assay at the local laboratory at screening for this study)
- Recent development of increasing jaundice (a total serum bilirubin concentration of above 85μmol/L) and coagulopathy (INR ≥1.5 or prothrombin activity<40%)
- Recent development of complications such as hepatic encephalopathy, or abrupt and obvious increase in ascites, or spontaneous bacterial peritonitis, or hepatorenal syndrome.
Key exclusion criteria (8 listed)
- Patient has concomitant other chronic viral infection (HCV or HIV)
- Patient has evidence of renal insufficiency defined as serum creatinine > 1.5 mg/dL
- Patient has medical condition that requires concurrent use of systemic prednisolone or other immunosuppressive agent (including chemotherapeutic agent)
- Patient is pregnant or breastfeeding or willing to be pregnant
- Patient has one or more additional known primary or secondary causes of liver disease, other than hepatitis B (e.g., alcoholism, autoimmune hepatitis, malignancy with hepatic involvement, hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's Disease, other congenital or metabolic conditions affecting the liver, congestive heart failure or other severe cardiopulmonary disease, etc.).
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 AlafenamideTenofovir alafenamide 25 mg/day orally | Drug | TAF |
| EntecavirEntecavir 0.5 mg/day orally | Drug | ETV |
| Tenofovir disoproxil fumarateTenofovir Disoproxil Fumarate 300 mg/day orally | Drug | TDF |
Primary outcome
Overall survival of ACLF subjects
Time frame: study day 1 through week 48
Overall survival in subjects with acute-on-chronic liver failure will be summarized and compared with control subjects through study day 28 and week 48.
7 secondary outcomes
Changes in serum HBV DNA levels
Time frame: at week 4 and 48 of treatment
Proportion of patients with hepatitis B e-Ag(HBe-Ag) loss or seroconversion
Time frame: at week 4 and 48 of treatment
Proportion of patients with HBs-Ag loss or seroconversion
Time frame: at week 4 and 48 of treatment
Proportion of patients with normal alanine aminotransferase(ALT)
Time frame: at week 4 and 48 of treatment
Liver function evaluation through Model for End-Stage Liver Disease (MELD) scores
Time frame: at week 4 and 48 of treatment
Proportion of patients with virologic breakthrough
Time frame: at week 4 and 48 of treatment
Proportion of patients with complete virologic response
Time frame: at week 4 and 48 of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2023.
- Derived from this study: PubMed 34126939Li J, Hu C, Chen Y, Zhang R, Fu S, Zhou M, Gao Z, Fu M, Yan T, Yang Y, Li J, Liu J, Chen T, Zhao Y, He Y. Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B. BMC Infect Dis. 2021 Jun 14;21(1):567. doi: 10.1186/s12879-021-06237-x.
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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.
Yingli He, M.D.,Ph.D principal investigator
First Affiliated Hospital Xi'an Jiaotong University
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatitis B and Virus Diseases, run by First Affiliated Hospital Xi'an Jiaotong University at 11 sites in China.
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 7 inclusion and 8 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: status not confirmed, as of the sponsor's last update on 9 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Juan Li, M.D. (18209272726, lijuan1996xx@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival of ACLF subjects (time frame: study day 1 through week 48). 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 NCT03640728, 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 9 Feb 2023.