Rheumatoid ArthritisPhase 4NCT01907230
Entecavir for Biological Agents Associated HBV Reactivation in Inflammatory Arthritis Patients
A Phase 4 study testing Entecavir in people with Rheumatoid Arthritis and Hepatitis B Reactivation, run by Taipei Veterans General Hospital, Taiwan at 1 site in Taiwan.
Trial summary
Antiviral prophylaxis can prevent the risk of biologic agents-associated HBV reactivation in hepatitis B inactive carriers and patients with past HBV infection Read more about this study
- Who is it for?
- Ages 20 to 90 years
- Conditions the study is for
- Rheumatoid Arthritis, Hepatitis B Reactivation, Exposure to Hepatitis B Virus
- What is being tested?
- Entecavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 115 participants
- Where
- 1 siteTaiwan
- Study dates
- 10 Sep 2013to 31 Dec 2019
- 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 20 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age : from 20 to 90 y/o.
- HBsAg-positive for more than 6 months and HBV DNA < 2000 IU/ml (Subgroup 1）or HBsAg-negative but anti-HBc positive with HBV DNA < 2000 IU/ml (Subgroup 2）.
- Inflammatory arthritis patients who plan to treat with biological agents, including Humira or Enbrel or Simponi or Orencia or Mabthera or Actemra; as first line biologic treatment is indicated.
Who cannot join
- HCV, HIV, or HDV coinfection.
- Uncontrolled HCC or other malignancy within 3 years.
- Decompensated liver cirrhosis (CTP score ≥ 7).
- Uremia patients under hemodialysis or continuous ambulatory peritoneal dialysis or patients with Ccr < 50 mL/min
- Pregnant or breastfeeding women.
- Women of child-bearing potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Division of Gastroenterology & Division of Allergy Immunology and Rheumatology, Taipei Veterans General Hospital
Taipei, 11217
About this study
Official title: Propylactic Use of Entecavir for Biological Agents Associated Hepatitis B Virus Reactivation in Inflammatory Arthritis Patients: a Randomized Controlled Trial
Antiviral prophylaxis can prevent the risk of biologic agents-associated HBV reactivation in hepatitis B inactive carriers and patients with past HBV infection
Read the detailed description
The risk of HBV reactivation is associated with the intensity of immunosuppression. Biological therapies block the action of biological products involved in immune-inflammatory pathogenesis of many diseases. However, these biologic agents induce a profound immunosuppression, and their use has been reported to be associated with HBV reactivation. Currently, the actual incidence of HBV reactivation in inflammatory arthritis patients who underwent biologic treatments (TNF-α blockades) is unclear, especially in inflammatory arthritis (IA) patients with past hepatitis B infection. In this study, we plan to enroll IA patients who are inactive HBV carriers (HBsAg-positive/ HBV viral loads <2000 IU/ml; subgroup 1), or have past HBV infection (HBsAg-negative/anti-HBc-positive/ HBV viral loads < 2000 IU/ml; subgroup 2); and first line biologic treatment (Humira or Enbrel or Simponi or Orencia or Mabthera or Actemra) is indicated. Patients will be randomized in a 1:1 ratio to receive either prophylactic or therapeutic entecavir treatment for each subgroup. In the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months. In the therapeutic group, patients will start entecavir therapy, 0.5 mg/day orally, when reactivation of HBV (pre-emptive treatment). HBV reactivation is defined as HBV viral loads > 2,000 IU/ml for 2 consecutive visits of one month apart. The main goal of the study is to delineate the incidence of HBV reactivation during and after biologic treatment in IA patients who are inactive HBV carriers or have past HBV infection, and tries to define the optimal HBV monitoring and antiviral prophylactic strategy in IA patients.
- Being tested
- Entecavir
- Keywords
- Rheumatoid arthritis, Inactive HBV carrier, Resolved Hepatitis B, HBV reactivation, Anti-tumor necrotic factor-alfa
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntecavirDrug
Also called Baraclude
In the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment (adjust dosage according to renal function) will be continued normally for 12 months (6 months after stopping biologic therapy or till restart another course of biologic treatment if the clinicians' judgment is minimal risk of reactivation after the first course of biologic agent treatment).
| Study group | Role | What they receive |
|---|---|---|
| Entecavir, Prophylactic group | Experimental | Participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months (6 months after stopping biologic therapy or till restart another course of biologic treatment if the clinicians' judgment is minimal risk of reactivation after the first course of biologic agent treatment). Receives: Drug: Entecavir |
| Control group (pre-emptive treatment) | No intervention | Patients will start entecavir therapy, 0.5 mg/day orally, when reactivation of HBV (defined as detectable HBV viral loads for 2 consecutive visits with at least one month apart), and continued entecavir treatment until undetectable HBV viral loads for 1 year (consistent with current APASL recommendation). |
What is being measured
The primary outcome is the main question the study is designed to answer.
HBV reactivation
The main goal of the study is to delineate the incidence of HBV reactivation during and after biologic treatment in IA patients who are inactive HBV carriers or have past HBV infection, and tries to define the optimal HBV monitoring and antiviral prophylactic strategy in IA patients.
Measured: 12 months after biologic treatment
Secondary outcomes (2)
HBsAg reverse seroconversion in occult HB patients.
Measured: 12 months after biologic treatment
Hepatitis flare (ALT > 100 U/L) related to biological treatments
Measured: 12 months after biologic treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2013 (estimated)
- Study start10 Sep 2013
- Primary completion31 Dec 2018
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by Taipei Veterans General Hospital, TaiwanThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 115 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taipei Veterans General Hospital, Taiwan
- Sponsor type
- Other government
- Responsible party
- Principal investigator, vghtpe user, Taipei Veterans General Hospital, Taiwan
- Investigators
- Yi-Hsiang Huang, MD, Ph.D., Principal investigator, Taipei Veterans General Hospital, Taiwan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01907230
- Sponsor's protocol ID
- AI463-962
- Status last verified
- Mar 2019
- First submitted
- 14 Jul 2013
- Last updated
- 13 Mar 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Propylactic Use of Entecavir for Biological Agents Associated Hepatitis B Virus Reactivation in Inflammatory Arthritis Patients: a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT01907230
- Acronym / sponsor ID
- AI463-962
- Keywords
- Rheumatoid arthritis, Inactive HBV carrier, Resolved Hepatitis B, HBV reactivation, Anti-tumor necrotic factor-alfa
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 115 participants (actual)
- Lead sponsor
- Taipei Veterans General Hospital, TaiwanOther government
- Study start
- 10 Sep 2013 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 24 Jul 2013 (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.
Antiviral prophylaxis can prevent the risk of biologic agents-associated HBV reactivation in hepatitis B inactive carriers and patients with past HBV infection
Detailed description
The risk of HBV reactivation is associated with the intensity of immunosuppression. Biological therapies block the action of biological products involved in immune-inflammatory pathogenesis of many diseases. However, these biologic agents induce a profound immunosuppression, and their use has been reported to be associated with HBV reactivation. Currently, the actual incidence of HBV reactivation in inflammatory arthritis patients who underwent biologic treatments (TNF-α blockades) is unclear, especially in inflammatory arthritis (IA) patients with past hepatitis B infection. In this study, we plan to enroll IA patients who are inactive HBV carriers (HBsAg-positive/ HBV viral loads <2000 IU/ml; subgroup 1), or have past HBV infection (HBsAg-negative/anti-HBc-positive/ HBV viral loads < 2000 IU/ml; subgroup 2); and first line biologic treatment (Humira or Enbrel or Simponi or Orencia or Mabthera or Actemra) is indicated. Patients will be randomized in a 1:1 ratio to receive either prophylactic or therapeutic entecavir treatment for each subgroup. In the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months. In the therapeutic group, patients will start entecavir therapy, 0.5 mg/day orally, when reactivation of HBV (pre-emptive treatment). HBV reactivation is defined as HBV viral loads > 2,000 IU/ml for 2 consecutive visits of one month apart. The main goal of the study is to delineate the incidence of HBV reactivation during and after biologic treatment in IA patients who are inactive HBV carriers or have past HBV infection, and tries to define the optimal HBV monitoring and antiviral prophylactic strategy in IA patients.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Entecavir, Prophylactic group | Experimental | Drug: EntecavirParticipants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months (6 months after stopping biologic therapy or till restart another course of biologic treatment if the clinicians' judgment is minimal risk of reactivation after the first course of biologic agent treatment). |
| Control group (pre-emptive treatment) | No intervention | –Patients will start entecavir therapy, 0.5 mg/day orally, when reactivation of HBV (defined as detectable HBV viral loads for 2 consecutive visits with at least one month apart), and continued entecavir treatment until undetectable HBV viral loads for 1 year (consistent with current APASL recommendation). |
Who may qualify
- Ages
- 20 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age : from 20 to 90 y/o.
- HBsAg-positive for more than 6 months and HBV DNA < 2000 IU/ml (Subgroup 1）or HBsAg-negative but anti-HBc positive with HBV DNA < 2000 IU/ml (Subgroup 2）.
- Inflammatory arthritis patients who plan to treat with biological agents, including Humira or Enbrel or Simponi or Orencia or Mabthera or Actemra; as first line biologic treatment is indicated.
Key exclusion criteria (6 listed)
- HCV, HIV, or HDV coinfection.
- Uncontrolled HCC or other malignancy within 3 years.
- Decompensated liver cirrhosis (CTP score ≥ 7).
- Uremia patients under hemodialysis or continuous ambulatory peritoneal dialysis or patients with Ccr < 50 mL/min
- Pregnant or breastfeeding women.
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 |
|---|---|---|
| EntecavirAlso: BaracludeIn the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment (adjust dosage according to renal function) will be continued normally for 12 months (6 months after stopping biologic therapy or till restart another course of biologic treatment if the clinicians' judgment is minimal risk of reactivation after the first course of biologic agent treatment). | Drug | Entecavir, Prophylactic group |
Primary outcome
HBV reactivation
Time frame: 12 months after biologic treatment
The main goal of the study is to delineate the incidence of HBV reactivation during and after biologic treatment in IA patients who are inactive HBV carriers or have past HBV infection, and tries to define the optimal HBV monitoring and antiviral prophylactic strategy in IA patients.
2 secondary outcomes
HBsAg reverse seroconversion in occult HB patients.
Time frame: 12 months after biologic treatment
Hepatitis flare (ALT > 100 U/L) related to biological treatments
Time frame: 12 months after biologic treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2019.
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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.
Yi-Hsiang Huang, MD, Ph.D. principal investigator
Taipei Veterans General Hospital, Taiwan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Entecavir in people with Rheumatoid Arthritis and Hepatitis B Reactivation, run by Taipei Veterans General Hospital, Taiwan at 1 site 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 3 inclusion and 6 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 13 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
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?
Results are not available in the source record.
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?
HBV reactivation (time frame: 12 months after biologic treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2019.