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

Phase 4

Completed

• Conditions: Acute on Chronic Liver Failure; Hepatitis B
• Interventions: Drug: Tenofovir disoproxil fumarate (TDF)

• Registration Number: NCT01074645
• Lead Sponsor: Govind Ballabh Pant Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11
• Primary Completion: 2009-06
• Status Verified: 2009-10
• Study Completion: 2009-10
• Study First Submitted: 2010-02-22
• Study First Submitted QC: 2010-02-23
• Last Update Submitted: 2010-02-23
• Study First Posted: 2010-02-24
• Last Update Posted: 2010-02-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	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)	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

Primary Outcome Measures

Name	Time	Method
Reduction in HBV DNA levels, survival	3 Month

Secondary Outcome Measures

Name	Time	Method
Improvement in CTP, MELD scores	3 Month

Trial Locations

Locations (1)

Department of Gastroenterology, GB Pant Hospital,; 🇮🇳 New Delhi, Delhi, India