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Randomized Controlled Trial of Tenofovir in Patients of Reactivation of Hepatitis B Presenting as Acute on Chronic Liver Failure (ACLF)

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ClinicalTrials.gov Identifier: NCT01074645
Recruitment Status : Completed
First Posted : February 24, 2010
Last Update Posted : February 24, 2010
Sponsor:
Information provided by:
Govind Ballabh Pant Hospital

Study Description
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Brief 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. 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.


Condition or disease Intervention/treatment Phase
Acute on Chronic Liver Failure Hepatitis B Drug: Tenofovir disoproxil fumarate (TDF) Phase 4

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
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
Study Start Date : November 2007
Actual Primary Completion Date : June 2009
Actual Study Completion Date : October 2009

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Arms and Interventions
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Arm Intervention/treatment
No Intervention: Placebo
Placebo was the multivitamin capsule which was similar in appearance as of Tenofovir disoproxil fumarate and was given once a day till 3 month.
 Drug: Tenofovir disoproxil fumarate (TDF)
Tenofovir 300mg/day for 3 month
Active Comparator: 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
 Drug: Tenofovir disoproxil fumarate (TDF)
Tenofovir 300mg/day for 3 month


Outcome Measures
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Primary Outcome Measures :
  1. Reduction in HBV DNA levels, survival [ Time Frame: 3 Month ]

Secondary Outcome Measures :
  1. Improvement in CTP, MELD scores [ Time Frame: 3 Month ]

Eligibility Criteria
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Ages Eligible for Study:   2 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
Contacts and Locations
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01074645


Locations
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India
Department of Gastroenterology, GB Pant Hospital,
New Delhi, Delhi, India, 110002
Sponsors and Collaborators
Govind Ballabh Pant Hospital
Investigators
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Principal Investigator: Shiv K Sarin, MD,DM G.B. Pant Hospital, New Delhi, India
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Shiv K Sarin, G.B. Pant Hospital, New Delhi, India
ClinicalTrials.gov Identifier: NCT01074645    
Other Study ID Numbers: Hitendra garg
First Posted: February 24, 2010    Key Record Dates
Last Update Posted: February 24, 2010
Last Verified: October 2009
Keywords provided by Govind Ballabh Pant Hospital:
Acute-on -chronic liver failure
Reactivation of hepatitis B
Spontaneous reactivation of chronic hepatitis B presenting as to acute-on-chronic liver failure
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis
Liver Failure
Hepatic Insufficiency
End Stage Liver Disease
Acute-On-Chronic Liver Failure
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
 RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Liver Failure, Acute
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents