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

Hepatitis B Clinical Trial

— ACLF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01074645
• Other study ID #: Hitendra garg
• Status: Completed
• Phase: Phase 4
• First received: February 22, 2010
• Last updated: February 23, 2010
• Start date: November 2007
• Est. completion date: October 2009

Study information

• Verified date: October 2009
• Source: Govind Ballabh Pant Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: India: Drugs Controller General of India
• Study type: Interventional

Clinical 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. 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: October 2009
• Est. primary completion date: June 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 75 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute on Chronic Liver Failure
• End Stage Liver Disease
• Hepatitis
• Hepatitis A
• Hepatitis B
• Liver Failure

Intervention

Drug:
• Tenofovir disoproxil fumarate (TDF)
Tenofovir 300mg/day for 3 month

Locations

Country	Name	City	State
India	Department of Gastroenterology, GB Pant Hospital,	New Delhi	Delhi

Sponsors (1)

Lead Sponsor	Collaborator
Govind Ballabh Pant Hospital

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in HBV DNA levels, survival		3 Month	Yes
Secondary	Improvement in CTP, MELD scores		3 Month	Yes