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

NCT01074645 | Completed Phase 4 DMC

• 1 other identifier: Hitendra garg
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Reduction in HBV DNA levels, survival

  3 Month

Secondary Outcomes (1)

• Improvement in CTP, MELD scores

  3 Month

Study Arms (2)

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.

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

Drug: Tenofovir disoproxil fumarate (TDF)

Interventions

Tenofovir disoproxil fumarate (TDF) DRUG

Tenofovir 300mg/day for 3 month

Placebo; Tenofovir disoproxil fumarate (TDF)

Eligibility Criteria

• Age: 2 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Govind Ballabh Pant Hospital: lead

Study Sites (1)

Department of Gastroenterology, GB Pant Hospital,

New Delhi, National Capital Territory of Delhi, 110002, India

Location

Related Publications (1)

• 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.

  PMID: 21294143 DERIVED

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure; Hepatitis B

Interventions

Tenofovir

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Shiv K Sarin, MD,DM

  G.B. Pant Hospital, New Delhi, India

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: February 22, 2010
• First Posted: February 24, 2010
• Study Start: November 1, 2007
• Primary Completion: June 1, 2009
• Study Completion: October 1, 2009
• Last Updated: February 24, 2010

Record last verified: 2009-10

Locations

IN (1)