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A Randomized Controlled Trial of Lamivudine in Acute Hepatitis B

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00380614
Recruitment Status : Completed
First Posted : September 26, 2006
Last Update Posted : September 26, 2006
Information provided by:
Maulana Azad Medical College

Brief Summary:
Since a proportion of patients with Acute Viral Hepatitis-B develop severe hepatitis and fulminant hepatic failure, it is logical to believe that a rapid reduction in the HBV DNA levels by using antiviral agents could result in a less intense host response against the hepatitis B virus. However, the experience with lamivudine treatment of immunocompetent patients with AVH-B is limited.The aim of the present study was to evaluate the efficacy, utility and safety of lamivudine in treating immunocompetent patients with AVH-B.

Condition or disease Intervention/treatment Phase
Hepatitis B Drug: Lamivudine Phase 4

Detailed Description:

The diagnosis of acute hepatitis B was based on recent onset acute illness including prodromal symptoms, jaundice and other typical symptoms. The laboratory investigations supporting the diagnosis of acute hepatitis included the presence of >2.5 times the upper limit of serum alanine aminotransferase (ALT) and serum bilirubin, and positive IgM anti-HBc test. Ultrasound, and esophagogastroduodenoscopy was done to look for any evidence of chronic liver disease. All patients had normal alpha-fetoprotein levels.

Co-infection with hepatitis A, C, D, E and human immunodeficiency virus (HIV) infection was looked for by appropriate serologic tests conducted within 7 days of presentation.

Patients with co-infection, a history of hepatotoxic drug intake or alcohol use >20g/day, or any evidence of chronic liver disease in the past, at presentation or during follow-up were excluded. Patients were also excluded if they had serum bilirubin < 5 mg/dl at presentation.

Patients were classified as severe AVH-B if they fulfilled any two of the following criteria: (1) hepatic encephalopathy; (2) serum bilirubin ≥10.0 mg/dl; and (3) international normalized ratio (INR) ≥1.6.

The patients were randomized into 2 groups: Group 1: Treatment with lamivudine 100 mg daily for 3 months, Group 2: Placebo. Randomization was done using random number table. The initial study and randomization was planned to enroll 120 patients or continue the study till three years, whichever was earlier. Individual rather than block randomization was done The investigators as well as the patients were blinded to the randomisation. The patients in the placebo group received a placebo pill.

All patients were monitored during treatment for clinical evidence and grade of hepatic encephalopathy, impaired coagulation (abnormal international normalized ratio, IINR), AST/ALT, serum albumin bilirubin levels every week for the first month and then monthly. HBV serology, including serum HBsAg, HBeAg, and anti-HBe were checked at baseline and every 3 months. Anti-HBs titres were checked at 6 and 12 months. Quantitative HBV DNA assay was performed on day 0, day 4, week 1, week 2, week 3, week 4, then every month for the next 2 months and then every 3 months for 12 months.

All patients were followed for at least 12 months after the onset of AVH-B. Development of protective anti-HBs(>10 IU/L) was specifically looked for.

Exacerbation of chronic hepatitis B was excluded by investigating thoroughly for any evidence of chronic liver disease by Ultrasound, Upper GI endoscopy, or low albumin at presentation. Ultrasound was repeated at 6 and 12 months, and if there was any suspicion Upper GI endoscopy was also repeated. LFTS were done at every hospital visit.

HBsAg, HBeAg, IgM anti-HBc, anti-HBs, and anti-HBe were tested by commercially available enzyme-linked immunoassays. Serum quantitative HBV DNA assay was performed by use of an ultra sensitive Hybrid capture assay [Digene Labs, USA] that has a lower limit of detection of 4,700 copies/ml. An arbitrary value of 4,700 copies/ml was assigned to values < 4,700 copies/ml for analysis purposes. In such patients HBV DNA was done by an in-house qualitative PCR test to indicate negativity or positivity of viral DNA. The lower limit of detection was 600 copies/ml.

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Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Study Start Date : January 2002
Study Completion Date : March 2005

Resource links provided by the National Library of Medicine

Drug Information available for: Lamivudine

Primary Outcome Measures :
  1. clinical improvement
  2. biochemical improvement

Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of acute hepatitis B
  • Bilirubin > 5 mg/dl at presentation.

Exclusion Criteria:

  • Patients with co-infection, a history of hepatotoxic drug intake or alcohol use >20g/day, or any evidence of chronic liver disease in the past, at presentation or during follow-up

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00380614

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G.B. Pant Hospital
New Delhi, Delhi, India, 110002
Sponsors and Collaborators
Maulana Azad Medical College
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Principal Investigator: Shiv K Sarin, MD, DM G.B. Pant Hospital, New Delhi, India
Layout table for additonal information Identifier: NCT00380614    
Other Study ID Numbers: Ethical/Path/GBPH/805
First Posted: September 26, 2006    Key Record Dates
Last Update Posted: September 26, 2006
Last Verified: September 2006
Keywords provided by Maulana Azad Medical College:
Acute Hepatitis B, Lamivudine
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Anti-HIV Agents