HBV/HCV Co-infectionNCT04405011
NUC in Preventing HBV Reactivation in HCV/HBV Co-infected Patients Receiving DAA for CHC
A study testing 24-week Entecavir and 12-week Entecavir in people with HBV/HCV Co-infection, run by National Taiwan University Hospital at 2 sites in Taiwan.
Trial summary
HBV reactivation is common in HCV/HBV coinfected patients receiving DAA therapy for chronic hepatitis C. How to prevent HBV reactivation remains unclear. In this trial, we aim to investigate whether prophylactic nucleos(t)ide analogue (NUC) at the start of DAA could prevent HBV reactivation or not. Read more about this study
- Who is it for?
- Ages 20 to 70 years
- Conditions the study is for
- HBV/HCV Co-infection
- What is being tested?
- 24-week Entecavir and 12-week Entecavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 2 sitesTaiwan
- Study dates
- 1 Aug 2018to 28 Dec 2020
- Phase
- Interventional
- 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 20 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥20 years;
- Anti-HCV positive and HCV RNA >1000 IU/ml;
- Any HCV genotype; all received 12 weeks of DAA treatment.
- Treatment naïve or experienced of pegylated interferon/ribavirin;
- Concurrent HBV infection which is defined by positive HBsAg for at least 6 months.
Who cannot join
- History of treatment regimen that included any kind of direct antiviral agents;
- Presence of other etiology of chronic hepatitis including HIV, autoimmune hepatitis, NASH, etc;
- Uncontrolled diabetes mellitus (Hba1c >8.5);
- Current evidence or suspicion of malignancy;
- Severe cardiovascular or other severe comorbid diseases;
- Autoimmune disorders;
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- Presence of liver cirrhosis clinically or pathologically;
- Any one of following hematology or biochemical or clinical abnormalities:
- AST/ALT >10x ULN, Albumin <3.5g/dL, Bilirubin >2.5mg/dL, eGFR <30 ml/min/1.73m2, prothrombin time prolongation >4 sec or INR >1.7, platelet count <100 x 103 uL, and history or presence of ascites or hepatic encephalopathy.
- Child-bearing age women without the willing to contraceptive control; pregnant women or lactating women.
Trial locations and contacts
2 sites in 1 country.
Taiwan2 sites, 2 recruiting
- Recruiting
National Taiwan University Hospital
Taipei, 100
Chun-Jen Liu, MDPHD, 0972651071, cjliu@ntu.edu.tw
- Recruiting
TC Chen
Taipei, 100
About this study
Official title: Role of Nucleoside Analogue in Preventing Clinical Reactivation of HBV in HCV/HBV Co-infected Patients Receiving DAA Therapy for Chronic Hepatitis C
HBV reactivation is common in HCV/HBV coinfected patients receiving DAA therapy for chronic hepatitis C. How to prevent HBV reactivation remains unclear. In this trial, we aim to investigate whether prophylactic nucleos(t)ide analogue (NUC) at the start of DAA could prevent HBV reactivation or not. And whether prolonged NUC prophylaxis (24 weeks) would be better than 12-week prophylaxis. This will be a three-arm, open-label, randomized, active controlled, study. Totally, 60 HBV/HCV co-infected treatment-naïve or treatment-experienced patients without decompensated liver cirrhosis will be included in this study. Group 1 patients (n=20) will receive 12-week ETV from the start of DAA therapy. Group 2 patients (n=20) will receive 24-week ETV from the start of DAA till 12 weeks after end of DAA. Group 3 patients (n=20) will not receive ETV during the period of DAA and will serve as controls. The rate of HBV reactivation and clinical reactivation will be compared among 3 groups of patients. Expected outcomes: The rate of HBV reactivation and clinical reactivation will be lower in the ETV prophylaxis group, and will be the lowest in the group receiving 24-week ETV prophylaxis.
Read the detailed description
We will determine the incidence of virologic and clinical reactivation of HBV during DAA treatment for CHC, in two prophylactic groups versus control group. We will also examine whether extending the duration of prophylactic NUC would be more beneficial than the 3-month prophylaxis regimen.
Patients with the following criteria will be enrolled: age ≥20 years; anti-HCV positive and HCV RNA >1000 IU/ml; any HCV genotype; all received 12 weeks of DAA treatment; treatment naïve or experienced of pegylated interferon/ribavirin; concurrent HBV infection which is defined by positive HBsAg for at least 6 months. Patients with the following criteria will be excluded: history of treatment regimen that included any kind of direct antiviral agents; presence of other etiology of chronic hepatitis including HIV, autoimmune hepatitis, NASH, etc; uncontrolled diabetes mellitus (Hba1c >8.5); current evidence or suspicion of malignancy; severe cardiovascular or other severe comorbid diseases; autoimmune disorders; presence of liver cirrhosis clinically or pathologically; any one of following hematology or biochemical or clinical abnormalities: AST/ALT >10x ULN, Albumin <3.5g/dL, Bilirubin >2.5mg/dL, eGFR <30 ml/min/1.73m2, prothrombin time prolongation >4 sec or INR >1.7, platelet count <100 x 103 uL, and history or presence of ascites or hepatic encephalopathy; child-bearing age women without the willing to contraceptive control; and pregnant women or lactating women.
Briefly, 60 HCV/HBV coinfected patients will be enrolled and randomized to receive 12-week DAA regimen for reimbursed for the the treatment of patients with CHC in Taiwan.
Entecavir (0.5mg; ETV) 1 # daily will be used in the prophylactic group. Group 1 patients (n=20) will receive 12-week ETV from the start of DAA therapy. Group 2 patients (n=20) will receive 24-week ETV from the start of DAA till 12 weeks after end of DAA. Group 3 patients (n=20) will not receive ETV during the period of DAA and serve as controls. The rate of HBV reactivation and clinical reactivation will be compared among 3 groups of patients.
The primary endpoint will be the incidence of virologic and clinical reactivation of HBV during DAA treatment for CHC. Secondary objectives include the rate of HBV virologic and clinical reactivation between 12-week versus 24-week entecavir (ETV) prophylaxis during and after DAA treatment; the profiles of serum HBV DNA/qHBsAg during and after DAA treatment; and sustained virological response at post-DAA treatment 12 weeks (SVR12).
The data will be expressed as percentages for category variables and as mean +- standard deviation for continuous variables. Category variables will be evaluated by Chi-square test or Fisher exact test. Student's t test or Mann-Whitney U test will be applied for comparison of the continuous variables. Multivariate analysis will be used to identify factors that are associated with HBV reactivation. A p value less than 0.05 is considered to be significant.
- Conditions
- HBV/HCV Co-infection
- Being tested
- 24-week Entecavir, 12-week Entecavir
- Keywords
- HCV,HBV
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
24-week EntecavirDrug
Also called Prophylaxis arm 1
Entecavir 0.5mg for 24 weeks will be delivered
12-week EntecavirDrug
Also called Prophylaxis arm 2
Entecavir for 12 weeks will be delivered and serve as the active comparator arm
| Study group | Role | What they receive |
|---|---|---|
| Entecavir 0.5mg daily for 24 weeks | Experimental | Entecavir will be delivered for 24-week and will be the experimental arm Receives: Drug: 24-week Entecavir |
| Entecavir 0.5mg daily for 12 weeks | Active comparator | 12-week entecavir will be served as active comparator Receives: Drug: 12-week Entecavir |
| Control | No intervention | Control group does not receive prophylactic ETV |
What is being measured
The primary outcome is the main question the study is designed to answer.
HBV virologic and clinical reactivation rates
The primary endpoint will be the incidence of virologic and clinical reactivation of HBV during DAA treatment for CHC.
Measured: 72 weeks
Secondary outcomes (3)
HBV reactivation rate: 12-week prophylaxis versus 24-week prophylaxis
12 weeks or 24 weeks of ETV prophylaxis in the control of HBV activity during and after DAA treatment
Measured: 72 weeks
Profiles of serum HBV DNA/qHBsAg during and after DAA treatment.
The profiles of HBV DNA and qHBsAg will be compared among 3 study groups
Measured: 72 weeks
Sustained virological response at post-DAA treatment 12 weeks (SVR12)
The SVR12 will be compared among 3 study groups
Measured: 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2020
- Study start1 Aug 2018
- Primary completion28 Dec 2020 (estimated)
- Study completion28 Dec 2020 (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 HBV/HCV Co-infectionStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chun-Jen Liu, MDPHD, Principal investigator, Department of Internal Medicine, NTUH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04405011
- Sponsor's protocol ID
- 201807069MINB
- Status last verified
- May 2020
- First submitted
- 17 Apr 2020
- Last updated
- 2 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Cheng PN, Liu CJ, Chen CY, Tseng KC, Lo CC, Peng CY, Lin CL, Chiu HC, Chiu YC, Chen PJ. Entecavir Prevents HBV Reactivation During Direct Acting Antivirals for HCV/HBV Dual Infection: A Randomized Trial. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2800-2808. doi: 10.1016/j.cgh.2021.11.032. Epub 2021 Dec 2.
PubMed 34864158
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Nucleoside Analogue in Preventing Clinical Reactivation of HBV in HCV/HBV Co-infected Patients Receiving DAA Therapy for Chronic Hepatitis C
- ClinicalTrials.gov ID
- NCT04405011
- Acronym / sponsor ID
- 201807069MINB
- Conditions
- HBV/HCV Co-infection
- Keywords
- HCV,HBV
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Aug 2018 (actual)
- Primary completion
- 28 Dec 2020 (estimated)
- Study completion
- 28 Dec 2020 (estimated)
- First posted
- 28 May 2020 (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 reactivation is common in HCV/HBV coinfected patients receiving DAA therapy for chronic hepatitis C. How to prevent HBV reactivation remains unclear. In this trial, we aim to investigate whether prophylactic nucleos(t)ide analogue (NUC) at the start of DAA could prevent HBV reactivation or not. And whether prolonged NUC prophylaxis (24 weeks) would be better than 12-week prophylaxis. This will be a three-arm, open-label, randomized, active controlled, study. Totally, 60 HBV/HCV co-infected treatment-naïve or treatment-experienced patients without decompensated liver cirrhosis will be included in this study. Group 1 patients (n=20) will receive 12-week ETV from the start of DAA therapy. Group 2 patients (n=20) will receive 24-week ETV from the start of DAA till 12 weeks after end of DAA. Group 3 patients (n=20) will not receive ETV during the period of DAA and will serve as controls. The rate of HBV reactivation and clinical reactivation will be compared among 3 groups of patients. Expected outcomes: The rate of HBV reactivation and clinical reactivation will be lower in the ETV prophylaxis group, and will be the lowest in the group receiving 24-week ETV prophylaxis.
Detailed description
We will determine the incidence of virologic and clinical reactivation of HBV during DAA treatment for CHC, in two prophylactic groups versus control group. We will also examine whether extending the duration of prophylactic NUC would be more beneficial than the 3-month prophylaxis regimen.
Patients with the following criteria will be enrolled: age ≥20 years; anti-HCV positive and HCV RNA >1000 IU/ml; any HCV genotype; all received 12 weeks of DAA treatment; treatment naïve or experienced of pegylated interferon/ribavirin; concurrent HBV infection which is defined by positive HBsAg for at least 6 months. Patients with the following criteria will be excluded: history of treatment regimen that included any kind of direct antiviral agents; presence of other etiology of chronic hepatitis including HIV, autoimmune hepatitis, NASH, etc; uncontrolled diabetes mellitus (Hba1c >8.5); current evidence or suspicion of malignancy; severe cardiovascular or other severe comorbid diseases; autoimmune disorders; presence of liver cirrhosis clinically or pathologically; any one of following hematology or biochemical or clinical abnormalities: AST/ALT >10x ULN, Albumin <3.5g/dL, Bilirubin >2.5mg/dL, eGFR <30 ml/min/1.73m2, prothrombin time prolongation >4 sec or INR >1.7, platelet count <100 x 103 uL, and history or presence of ascites or hepatic encephalopathy; child-bearing age women without the willing to contraceptive control; and pregnant women or lactating women.
Briefly, 60 HCV/HBV coinfected patients will be enrolled and randomized to receive 12-week DAA regimen for reimbursed for the the treatment of patients with CHC in Taiwan.
Entecavir (0.5mg; ETV) 1 # daily will be used in the prophylactic group. Group 1 patients (n=20) will receive 12-week ETV from the start of DAA therapy. Group 2 patients (n=20) will receive 24-week ETV from the start of DAA till 12 weeks after end of DAA. Group 3 patients (n=20) will not receive ETV during the period of DAA and serve as controls. The rate of HBV reactivation and clinical reactivation will be compared among 3 groups of patients.
The primary endpoint will be the incidence of virologic and clinical reactivation of HBV during DAA treatment for CHC. Secondary objectives include the rate of HBV virologic and clinical reactivation between 12-week versus 24-week entecavir (ETV) prophylaxis during and after DAA treatment; the profiles of serum HBV DNA/qHBsAg during and after DAA treatment; and sustained virological response at post-DAA treatment 12 weeks (SVR12).
The data will be expressed as percentages for category variables and as mean +- standard deviation for continuous variables. Category variables will be evaluated by Chi-square test or Fisher exact test. Student's t test or Mann-Whitney U test will be applied for comparison of the continuous variables. Multivariate analysis will be used to identify factors that are associated with HBV reactivation. A p value less than 0.05 is considered to be significant.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Entecavir 0.5mg daily for 24 weeks | Experimental | Drug: 24-week EntecavirEntecavir will be delivered for 24-week and will be the experimental arm |
| Entecavir 0.5mg daily for 12 weeks | Active comparator | Drug: 12-week Entecavir12-week entecavir will be served as active comparator |
| Control | No intervention | –Control group does not receive prophylactic ETV |
Who may qualify
- Ages
- 20 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥20 years;
- Anti-HCV positive and HCV RNA >1000 IU/ml;
- Any HCV genotype; all received 12 weeks of DAA treatment.
- Treatment naïve or experienced of pegylated interferon/ribavirin;
- Concurrent HBV infection which is defined by positive HBsAg for at least 6 months.
Key exclusion criteria (10 listed)
- History of treatment regimen that included any kind of direct antiviral agents;
- Presence of other etiology of chronic hepatitis including HIV, autoimmune hepatitis, NASH, etc;
- Uncontrolled diabetes mellitus (Hba1c >8.5);
- Current evidence or suspicion of malignancy;
- Severe cardiovascular or other severe comorbid diseases;
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 |
|---|---|---|
| 24-week EntecavirAlso: Prophylaxis arm 1Entecavir 0.5mg for 24 weeks will be delivered | Drug | Entecavir 0.5mg daily for 24 weeks |
| 12-week EntecavirAlso: Prophylaxis arm 2Entecavir for 12 weeks will be delivered and serve as the active comparator arm | Drug | Entecavir 0.5mg daily for 12 weeks |
Primary outcome
HBV virologic and clinical reactivation rates
Time frame: 72 weeks
The primary endpoint will be the incidence of virologic and clinical reactivation of HBV during DAA treatment for CHC.
3 secondary outcomes
HBV reactivation rate: 12-week prophylaxis versus 24-week prophylaxis
Time frame: 72 weeks
Profiles of serum HBV DNA/qHBsAg during and after DAA treatment.
Time frame: 72 weeks
Sustained virological response at post-DAA treatment 12 weeks (SVR12)
Time frame: 72 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2020.
- Derived from this study: PubMed 34864158Cheng PN, Liu CJ, Chen CY, Tseng KC, Lo CC, Peng CY, Lin CL, Chiu HC, Chiu YC, Chen PJ. Entecavir Prevents HBV Reactivation During Direct Acting Antivirals for HCV/HBV Dual Infection: A Randomized Trial. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2800-2808. doi: 10.1016/j.cgh.2021.11.032. Epub 2021 Dec 2.
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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.
Chun-Jen Liu, MDPHD principal investigator
Department of Internal Medicine, NTUH
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 24-week Entecavir and 12-week Entecavir in people with HBV/HCV Co-infection, run by National Taiwan University Hospital at 2 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: status not confirmed, as of the sponsor's last update on 2 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. 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 Chun-Jen Liu (0972651071, cjliu@ntu.edu.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HBV virologic and clinical reactivation rates (time frame: 72 weeks). 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 NCT04405011, 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 2 Jul 2020.