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

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

Tracking Information

• First Submitted Date: February 22, 2010
• First Posted Date: February 24, 2010
• Last Update Posted Date: February 24, 2010
• Study Start Date: November 2007
• Actual Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 23, 2010): Reduction in HBV DNA levels, survival [ Time Frame: 3 Month ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures (submitted: February 23, 2010): Improvement in CTP, MELD scores [ Time Frame: 3 Month ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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 Provided
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment

Condition

• Acute on Chronic Liver Failure
• Hepatitis B

Intervention

Drug: Tenofovir disoproxil fumarate (TDF)

Tenofovir 300mg/day for 3 month

Study Arms

• 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.
  Intervention: Drug: Tenofovir disoproxil fumarate (TDF)
• 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
  Intervention: Drug: Tenofovir disoproxil fumarate (TDF)

• Publications *: 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. Erratum in: Hepatology. 2011 Sep 2;54(3):1114.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 23, 2010): 27
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: October 2009
• Actual Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 75 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India

Administrative Information

• NCT Number: NCT01074645
• Other Study ID Numbers: Hitendra garg
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Shiv K Sarin, G.B. Pant Hospital, New Delhi, India
• Study Sponsor: Govind Ballabh Pant Hospital
• Collaborators: Not Provided

Investigators

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

• PRS Account: Govind Ballabh Pant Hospital
• Verification Date: October 2009