Lamivudine for Chronic Hepatitis B

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001457
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: September 2005
  Purpose

Chronic hepatitis B is a disease of the liver caused by the hepatitis B virus. It affects nearly 1 million Americans. Approximately 25% of patients with chronic hepatitis B will develop liver cirrhosis and 5% of patients will develop liver cancer.

Presently, two medications have been shown effective in the treatment of hepatitis B: lamivudine and alpha interferon. Alpha interferon (an antiviral drug that acts through the immune system) is given by injection once daily or three times a week for four to six months. Lamivudine (also known as 3-thiacytidine: 3TC) is an antiviral medication given as a pill once a day for twelve months. These treatments have been known to provide long-term improvement in one third of patients receiving them.

In previous research, the drug lamivudine was shown to stop the growth of the hepatitis B virus and to lead marked decreases in the levels of hepatitis B virus and to improvements in the disease in 50 to 70% of patients. However, once lamivudine therapy was discontinued the virus returned to levels noted before the therapy began. In those studies lamivudine was given for 3 to 12 months then discontinued. This study will investigate the safety and effectiveness of long-term therapy with lamivudine.

This study will select 60 patients diagnosed with hepatitis B. After a thorough medical examination and liver biopsy, subjects will be given lamivudine. The drug will be taken by mouth in tablet form (100 mg) once a day for up to 5 years. Subjects will undergo regular check-ups and after 1 year of therapy be admitted to the Clinical Center for another medical examination and liver biopsy to assess progress. Patients who have benefitted from the therapy will continue taking the medication for up to 5 years. A third liver biopsy will be done during the last year of treatment. The effectiveness of lamivudine will be determined by whether levels of hepatitis B virus decrease in the blood, whether liver enzymes improve, and whether inflammation and scarring decreases in the liver biopsies.


Condition Intervention Phase
Chronic Hepatitis B
Chronic Hepatitis D
Glomerulonephritis
Polyarteritis Nodosa
Drug: Lamivudine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: Lamivudine for Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 60
Study Start Date: September 1995
Estimated Study Completion Date: September 2005
Detailed Description:

To assess the safety, antiviral activity and clinical benefit of lamivudine (3-thiacytidine: 3TC) in chronic hepatitis B, we will treat 60 patients with oral lamivudine in a dose of 100 mg daily for up to five years. Lamivudine is a nucleoside analogue which is used extensively in patients with HIV infection and is being studied in controlled trials in chronic hepatitis B. In this study, we will evaluate lamivudine in patients with four different forms of chronic hepatitis B: (A) Atypical serology (HBeAg negative), (B) extra-hepatic manifestations, (C) chronic delta hepatitis, (D) typical HBeAg- positive chronic hepatitis B. After evaluation and liver biopsy, patients will receive lamivudine, 100 mg orally once daily for 1 year, being monitored at regular intervals for symptoms of liver disease, side effects of lamivudine, serum biochemical and hematologic indices, and serologic markers of hepatitis B (and D) virus replication. At one year, patients will have a repeat medical evaluation and liver biopsy. If there is virologic, biochemical or histologic evidence of benefit, therapy will be continued thereafter for up to 5 years. Patients who develop viral resistance to lamivudine may be offered therapy with higher doses of lamivudine (300 mg per day). The activity of lamivudine will be assessed by changes in levels of HBV DNA or HDV RNA during treatment and its efficacy by loss of viral markers and improvements in aminotransferases and liver histology.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

Age 18 years or above, male or female.

Known presence of HBsAg in serum for at least 6 months.

Liver biopsy histology showing chronic hepatitis with or without cirrhosis.

Previous therapy with alpha interferon without a lasting effect or intolerance to alpha interferon, due to side effects.

Written informed consent.

Group A: For patients with chronic hepatitis B with atypical serology: absence of HBeAg from serum despite elevations in serum aminotransferases, such as that the average levels are greater than 55 U/L (approximately 1.3 times the upper limit of the normal range) based upon two determinations taken at least one month apart during the 6 months before entry.

Group B: For patients with glomerulonephritis: proteinuria of greater than 1 gm per 24 hours. For patients with polyarteritis, radiological proof of arteritis and involvement of at least on organ system outside of the liver.

Group C: For patients with chronic delta hepatitis: anti-HDV in serum and HDV antigen in liver biopsy or HDV RNA in serum and elevations in serum aminotransferases, such that the average levels are greater than 55 U/L based upon two determinations taken at least one month apart during the 6 months before entry.

Group D: For patients with chronic hepatitis B and typical serology: HBeAg and HBV DNA in serum but ineligibility to enter the multicenter trial of lamivudine either because of previous receipt of interferon and intolerable side effects, refusal to receive interferon again, because of normal serum aminotransferases, or lack of availability of the trial.

EXCLUSION CRITERIA

Pregnant or if capable of bearing or fathering children must practice adequate contraception.

Significant systemic illnesses other than liver diseases, including congestive heart failure, renal failure, chronic pancreatitis, diabetes mellitus with poor control.

Pre-existing bone marrow compromise: hematocrit must be greater than 30%, white blood cell count must be greater than 2000 mm(3), platelets must be greater than 70,000 mm(3).

Creatinine clearance must be greater than 50 cc/min.

A history of clinically apparent pancreatitis or evidence of subclinically pancreatitis as shown by serum amylase values twice the upper limits of the normal range and abnormalities of the pancreas on computerized tomography or other imaging studies of the abdomen.

Irreversibly severe cirrhosis as defined by Child's stage C.

Presence of anti-HIV or anti-HCV with HCV RNA in serum.

Immunosuppressive therapy requiring use of more than 10 mg of prednisone (or its equivalent) per day.

Other antiviral therapy for chronic hepatitis B within the previous 3 months.

Sensory or motor neuropathy apparent from medical history and physical examination.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001457

Locations
United States, Maryland
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001457     History of Changes
Other Study ID Numbers: 950199, 95-DK-0199
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Nucleoside Analogues
Delta Hepatitis
Glomerulonephritis
Polyarteritis Nodosa
Hepatitis Mutants
3TC
Chronic Hepatitis B
Chronic Hepatitis D
Cirrhosis
Lamivudine

Additional relevant MeSH terms:
Hepatitis D
Hepatitis D, Chronic
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Glomerulonephritis
Polyarteritis Nodosa
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Nephritis
Kidney Diseases
Urologic Diseases
Arteritis
Vascular Diseases
Cardiovascular Diseases
Vasculitis
Systemic Vasculitis
Skin Diseases, Vascular
Skin Diseases
Lamivudine
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on October 16, 2014