A Study of Zidovudine in HIV-Infected Patients With Liver Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001001
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

To examine the pharmacokinetics (blood levels) and bioavailability of zidovudine (AZT) given to patients with HIV infection and chronic liver disease. The specific aim of the study is to provide data permitting the development of guidelines for use of AZT in patients with mild, moderate, or severe liver disease.

AZT is the only antiviral agent that has been shown to be effective in patients with severe HIV infection. However, AZT is largely eliminated from the body through a biochemical reaction that takes place in the liver, and it is possible that patients with underlying liver disease may have altered AZT pharmacokinetics and may metabolize AZT differently, with the result that they are susceptible to an increased risk of serious drug toxicity. This study will examine the pharmacokinetics, elimination, and metabolism of AZT in patients with liver disease. Guidelines developed from the data will be helpful in managing AZT treatment of these HIV-infected persons and will indicate whether the dose of AZT administered should be adjusted to compensate for any changes in its bioavailability and/or pharmacokinetics.


Condition Intervention
HIV Infections
Liver Diseases
Drug: Zidovudine

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Clinical Study Examining the Pharmacokinetics and Bioavailability of Azidothymidine (AZT, Zidovudine) in Patients With Human Immunodeficiency Virus (HIV) Infection and Hepatic Disease

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 39
Study Completion Date: May 1990
Detailed Description:

AZT is the only antiviral agent that has been shown to be effective in patients with severe HIV infection. However, AZT is largely eliminated from the body through a biochemical reaction that takes place in the liver, and it is possible that patients with underlying liver disease may have altered AZT pharmacokinetics and may metabolize AZT differently, with the result that they are susceptible to an increased risk of serious drug toxicity. This study will examine the pharmacokinetics, elimination, and metabolism of AZT in patients with liver disease. Guidelines developed from the data will be helpful in managing AZT treatment of these HIV-infected persons and will indicate whether the dose of AZT administered should be adjusted to compensate for any changes in its bioavailability and/or pharmacokinetics.

Patients are assessed and stratified according to liver function and severity of liver disease. Patients receive an intravenous (IV) dose of AZT on the first day of the study, followed by an oral dose 24 hours later on the second day of the study. Patients fast for 8 hours prior to each dose and for 2 hours after each dose. Liver function tests are repeated on the first day of the study. In each patient, serial measurements of serum and urine AZT and its metabolite, 3'-azido-3'-deoxy-5'-glucuronylthymidine (GAZT), are monitored after both doses.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed after completion of day 2 of study:

  • Prior medications may be resumed.

Concurrent Treatment:

Allowed after completion of day 2 of study:

  • Cytotoxic chemotherapy or radiation therapy for Kaposi's sarcoma.

The study will be divided into three groups of cooperative patients according to mild, moderate, or severe liver disease. Severity of disease will be assessed within 7 days of entry into the study according to laboratory values. Patients must have normal kidney function. No medications should be taken for 48 hours prior to entering the study. Hemophiliacs are included.

Prior Medication:

Allowed:

  • Zidovudine (AZT) if discontinued at least 48 hours prior to study entry.

Exclusion Criteria

Co-existing Condition:

Patients will be excluded from the study if unacceptable toxicity develops or if an illness requiring concurrent treatment develops.

Concurrent Medication:

Excluded within 48 hours of study entry:

  • All medications. Medication may be resumed after completion of day 2 of the study.

Concurrent Treatment:

Excluded within 48 hours of study entry:

  • All treatments. Treatment may be resumed after completion of day 2 of the study.

Patients will be excluded for the following reasons:

  • Presence of active opportunistic infections, with the exception of active or chronic hepatitis B virus or hepatitis D virus infection, or ongoing therapy for an opportunistic infection.
  • Thrombocytopenia, with platelets less than 50000 platelets/mm3.
  • Neutropenia, with polymorphonuclear leukocytes less than 1000 cells/mm3.
  • Renal insufficiency, with creatinine greater than 1.5 mg/dl.
  • Acute viral hepatitis within 30 days of the study.
  • Patients who are expected to be noncompliant or who are unwilling to sign an informed consent statement.

Prior Medication:

Excluded within 48 hours of study entry:

  • All medications. Medication may be resumed after completion of day 2 of the study.

Prior Treatment:

Excluded within 30 days of study entry:

  • Cytotoxic chemotherapy or radiation therapy for Kaposi's sarcoma. Treatment may be resumed after completion of day 2 of the study.

Active drug or alcohol abuse.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00001001

Locations
United States, Massachusetts
Boston Med Ctr
Boston, Massachusetts, United States, 02118
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, United States, 01655
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
United States, Pennsylvania
Milton S Hershey Med Ctr
Hershey, Pennsylvania, United States, 170330850
United States, Washington
Univ of Washington
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Investigators
Study Chair: Lemon SM
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00001001     History of Changes
Other Study ID Numbers: ACTG 062, 11036
Study First Received: November 2, 1999
Last Updated: March 15, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Liver
Liver Diseases
Liver Function Tests
HIV Seropositivity
Acquired Immunodeficiency Syndrome
Zidovudine
Biological Availability

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Liver Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Digestive System Diseases
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 16, 2014