Acute on Chronic Liver FailurePhase 4ACLFNCT01074645
Randomized Controlled Trial of Tenofovir in Patients of Reactivation of Hepatitis B Presenting as Acute on Chronic Liver Failure
A Phase 4 study testing Tenofovir disoproxil fumarate (TDF) in people with Acute on Chronic Liver Failure and Hepatitis B, run by Govind Ballabh Pant Hospital at 1 site in India.
Trial summary
Background: Reactivation of hepatitis B is a well-characterized syndrome marked by the abrupt reappearance or rise of hepatitis B virus (HBV) DNA in the serum of a patient with previously inactive or resolved HBV infection. Read more about this study
- Who is it for?
- Ages 2 to 75 years
- Conditions the study is for
- Acute on Chronic Liver Failure, Hepatitis B
- What is being tested?
- Tenofovir disoproxil fumarate (TDF)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteIndia
- Study dates
- Nov 2007to Oct 2009
- 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 2 to 75 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Reactivation of chronic hepatitis B characterized by rise in ALT level >5 times upper limit of normal along with HBV DNA level >105 copies/ml (~1.8x104 IU/ml) presenting as ACLF
- Acute hepatic insult
- Jaundice (bilirubin ≥5 mg/dL) and coagulopathy (INR>1.5)
- Complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease.
Who cannot join
- Superinfection with other viruses (Hepatitis E, A, D and C)
- Coexistent hepatocellular carcinoma (HCC)
- Portal vein thrombosis
- Coexistent renal impairment
- Pregnancy
- Co-infection with HIV infection or Patients received previous course of any antiviral
- Immunomodulator or cytotoxic/immunosuppressive therapy for chronic hepatitis or other illness within at least the preceding 12 month.
Trial locations and contacts
1 site in 1 country.
India1 site
Department of Gastroenterology, GB Pant Hospital,
New Delhi, National Capital Territory of Delhi, 110002
About this study
Official title: Tenofovir Reduces Morbidity and Mortality in Patients With Spontaneous Reactivation of Hepatitis B Presenting as Acute-on-chronic Liver Failure (ACLF): A Randomized Placebo Controlled Trial
Background: Reactivation of hepatitis B is a well-characterized syndrome marked by the abrupt reappearance or rise of hepatitis B virus (HBV) DNA in the serum of a patient with previously inactive or resolved HBV infection. Reactivation can be spontaneous, but is most commonly triggered by cancer chemotherapy, immune suppression, or alteration in immune function. Spontaneous acute exacerbation of chronic hepatitis B infection is seen with a cumulative probability of 15±37% after 4 years of follow-up.2 Significant number of patients of spontaneous acute exacerbation of chronic hepatitis B may present with very high ALT levels, jaundice and liver failure.3 This condition should be defined as acute-on-chronic liver failure (ACLF) according to a recent Asia-Pacific consensus recommendation.
The short term prognosis of patients of spontaneous acute exacerbation of chronic hepatitis B leading to ACLF like presentation is extremely poor, with a mortality of 30-70% in different series.8,9,10 Liver transplantation has been the only definitive therapy available to salvage this group of patients. However ,this is not readily available and affordable. Another therapeutic option is antiviral therapy but has limited data. The efficacy of lamivudine was evaluated and compared by historical control but was not found to be beneficial.8,9,10 However ,a study from Taiwan showed a survival benefit in a subgroup of patients who were on lamivudine and had baseline bilirubin below 342 mmol/L (20 mg/dL).11 Tenofovir disoproxil fumarate (TDF) is a potent, rapidly acting, oral acyclic nucleotide analogue, reverse transcriptase inhibitor that has been shown to be highly effective in suppressing hepatitis B virus replication.12 Tenofovir has also shown excellent activity against HBV in both LAM- naïve and LAM-resistant patients.13,14. Its efficacy has not been evaluated in patients of reactivation of hepatitis B who present as ACLF Hypothesis: The investigators hypothesis that Tenofovir reduces the morbidity and mortality in patients with Spontaneous reactivation of hepatitis B by reducing HBV DNA.
- Conditions
- Acute on Chronic Liver Failure, Hepatitis B
- Being tested
- Tenofovir disoproxil fumarate (TDF)
- Keywords
- Acute-on -chronic liver failure, Reactivation of hepatitis B, Spontaneous reactivation of chronic hepatitis B presenting as to acute-on-chronic liver failure
- Medical subject headings
- Acute-On-Chronic Liver Failure, Hepatitis B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tenofovir disoproxil fumarate (TDF)Drug
Tenofovir 300mg/day for 3 month
| Study group | Role | What they receive |
|---|---|---|
| Placebo | No intervention | Placebo was the multivitamin capsule which was similar in appearance as of Tenofovir disoproxil fumarate and was given once a day till 3 month. Receives: Drug: Tenofovir disoproxil fumarate (TDF) |
| Tenofovir disoproxil fumarate (TDF) | Active comparator | Tenofovir disoproxil fumarate (TDF) is a potent, rapidly acting, oral acyclic nucleotide analogue, reverse transcriptase inhibitor that has been shown to be highly effective in suppressing hepatitis B virus replication. Tenofovir has also shown excellent activity against HBV in both LAM- naïve and LAM-resistant patients. Its efficacy has not been evaluated in patients of reactivation of hepatitis B who present as ACLF Receives: Drug: Tenofovir disoproxil fumarate (TDF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in HBV DNA levels, survival
Measured: 3 Month
Secondary outcomes (1)
Improvement in CTP, MELD scores
Measured: 3 Month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2010 (estimated)
- Study startNov 2007
- Primary completionJun 2009
- Study completionOct 2009
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 Acute on Chronic Liver FailureStudies 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
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Govind Ballabh Pant Hospital
- Sponsor type
- Other government
- Investigators
- Shiv K Sarin, MD,DM, Principal investigator, G.B. Pant Hospital, New Delhi, India
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01074645
- Sponsor's protocol ID
- Hitendra garg
- Acronym
- ACLF
- Status last verified
- Oct 2009
- First submitted
- 22 Feb 2010
- Last updated
- 24 Feb 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Garg H, Sarin SK, Kumar M, Garg V, Sharma BC, Kumar A. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. Hepatology. 2011 Mar;53(3):774-80. doi: 10.1002/hep.24109. Epub 2011 Feb 3.
PubMed 21294143
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tenofovir Reduces Morbidity and Mortality in Patients With Spontaneous Reactivation of Hepatitis B Presenting as Acute-on-chronic Liver Failure (ACLF): A Randomized Placebo Controlled Trial
- ClinicalTrials.gov ID
- NCT01074645
- Acronym / sponsor ID
- ACLF / Hitendra garg
- Conditions
- Acute on Chronic Liver Failure, Hepatitis B
- Keywords
- Acute-on -chronic liver failure, Reactivation of hepatitis B, Spontaneous reactivation of chronic hepatitis B presenting as to acute-on-chronic liver failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Govind Ballabh Pant HospitalOther government
- Study start
- Nov 2007
- Primary completion
- Jun 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 24 Feb 2010 (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.
Background: Reactivation of hepatitis B is a well-characterized syndrome marked by the abrupt reappearance or rise of hepatitis B virus (HBV) DNA in the serum of a patient with previously inactive or resolved HBV infection. Reactivation can be spontaneous, but is most commonly triggered by cancer chemotherapy, immune suppression, or alteration in immune function. Spontaneous acute exacerbation of chronic hepatitis B infection is seen with a cumulative probability of 15±37% after 4 years of follow-up.2 Significant number of patients of spontaneous acute exacerbation of chronic hepatitis B may present with very high ALT levels, jaundice and liver failure.3 This condition should be defined as acute-on-chronic liver failure (ACLF) according to a recent Asia-Pacific consensus recommendation.
The short term prognosis of patients of spontaneous acute exacerbation of chronic hepatitis B leading to ACLF like presentation is extremely poor, with a mortality of 30-70% in different series.8,9,10 Liver transplantation has been the only definitive therapy available to salvage this group of patients. However ,this is not readily available and affordable. Another therapeutic option is antiviral therapy but has limited data. The efficacy of lamivudine was evaluated and compared by historical control but was not found to be beneficial.8,9,10 However ,a study from Taiwan showed a survival benefit in a subgroup of patients who were on lamivudine and had baseline bilirubin below 342 mmol/L (20 mg/dL).11 Tenofovir disoproxil fumarate (TDF) is a potent, rapidly acting, oral acyclic nucleotide analogue, reverse transcriptase inhibitor that has been shown to be highly effective in suppressing hepatitis B virus replication.12 Tenofovir has also shown excellent activity against HBV in both LAM- naïve and LAM-resistant patients.13,14. Its efficacy has not been evaluated in patients of reactivation of hepatitis B who present as ACLF Hypothesis: The investigators hypothesis that Tenofovir reduces the morbidity and mortality in patients with Spontaneous reactivation of hepatitis B by reducing HBV DNA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | No intervention | Drug: Tenofovir disoproxil fumarate (TDF)Placebo was the multivitamin capsule which was similar in appearance as of Tenofovir disoproxil fumarate and was given once a day till 3 month. |
| Tenofovir disoproxil fumarate (TDF) | Active comparator | Drug: Tenofovir disoproxil fumarate (TDF)Tenofovir disoproxil fumarate (TDF) is a potent, rapidly acting, oral acyclic nucleotide analogue, reverse transcriptase inhibitor that has been shown to be highly effective in suppressing hepatitis B virus replication. Tenofovir has also shown excellent activity against HBV in both LAM- naïve and LAM-resistant patients. Its efficacy has not been evaluated in patients of reactivation of hepatitis B who present as ACLF |
Who may qualify
- Ages
- 2 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Reactivation of chronic hepatitis B characterized by rise in ALT level >5 times upper limit of normal along with HBV DNA level >105 copies/ml (~1.8x104 IU/ml) presenting as ACLF
- Acute hepatic insult
- Jaundice (bilirubin ≥5 mg/dL) and coagulopathy (INR>1.5)
- Complicated within 4 weeks by ascites and/or encephalopathy in a patient with previously diagnosed or undiagnosed chronic liver disease.
Key exclusion criteria (7 listed)
- Superinfection with other viruses (Hepatitis E, A, D and C)
- Coexistent hepatocellular carcinoma (HCC)
- Portal vein thrombosis
- Coexistent renal impairment
- Pregnancy
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 (TDF)Tenofovir 300mg/day for 3 month | Drug | Placebo, Tenofovir disoproxil fumarate (TDF) |
Primary outcome
Reduction in HBV DNA levels, survival
Time frame: 3 Month
1 secondary outcome
Improvement in CTP, MELD scores
Time frame: 3 Month
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 24 Feb 2010.
- Derived from this study: PubMed 21294143Garg H, Sarin SK, Kumar M, Garg V, Sharma BC, Kumar A. Tenofovir improves the outcome in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure. Hepatology. 2011 Mar;53(3):774-80. doi: 10.1002/hep.24109. Epub 2011 Feb 3.
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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.
Shiv K Sarin, MD,DM principal investigator
G.B. Pant Hospital, New Delhi, India
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 Tenofovir disoproxil fumarate (TDF) in people with Acute on Chronic Liver Failure and Hepatitis B, run by Govind Ballabh Pant Hospital at 1 site in India.
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 4 inclusion and 7 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 24 Feb 2010. 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 India. 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?
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?
Reduction in HBV DNA levels, survival (time frame: 3 Month). 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 NCT01074645, 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 24 Feb 2010.