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

February 23, 2010 updated by: Govind Ballabh Pant Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Delhi
      • New Delhi, Delhi, India, 110002
        • Department of Gastroenterology, GB Pant Hospital,

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 75 years (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Reduction in HBV DNA levels, survival
Time Frame: 3 Month
3 Month

Secondary Outcome Measures

Outcome Measure
Time Frame
Improvement in CTP, MELD scores
Time Frame: 3 Month
3 Month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Govind Ballabh Pant Hospital

Investigators

  • Principal Investigator: Shiv K Sarin, MD,DM, G.B. Pant Hospital, New Delhi, India

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (ACTUAL)

June 1, 2009

Study Completion (ACTUAL)

October 1, 2009

Study Registration Dates

First Submitted

February 22, 2010

First Submitted That Met QC Criteria

February 23, 2010

First Posted (ESTIMATE)

February 24, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

February 24, 2010

Last Update Submitted That Met QC Criteria

February 23, 2010

Last Verified

October 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Hitendra garg

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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