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

Primary Purpose

HIV Infections, Liver Diseases

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Zidovudine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Liver, Liver Diseases, Liver Function Tests, HIV Seropositivity, Acquired Immunodeficiency Syndrome, Zidovudine, Biological Availability

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Boston Med Ctr
  • Univ of Massachusetts Med Ctr
  • Univ of North Carolina
  • Milton S Hershey Med Ctr
  • Univ of Washington

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 28, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00001001
Brief Title
A Study of Zidovudine in HIV-Infected Patients With Liver Disease
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 1990 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Liver Diseases
Keywords
Liver, Liver Diseases, Liver Function Tests, HIV Seropositivity, Acquired Immunodeficiency Syndrome, Zidovudine, Biological Availability

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Masking
None (Open Label)
Enrollment
39 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lemon SM
Official's Role
Study Chair
Facility Information:
Facility Name
Boston Med Ctr
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Univ of Massachusetts Med Ctr
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
Country
United States
Facility Name
Milton S Hershey Med Ctr
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
170330850
Country
United States
Facility Name
Univ of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
8593010
Citation
Moore KH, Raasch RH, Brouwer KL, Opheim K, Cheeseman SH, Eyster E, Lemon SM, van der Horst CM. Pharmacokinetics and bioavailability of zidovudine and its glucuronidated metabolite in patients with human immunodeficiency virus infection and hepatic disease (AIDS Clinical Trials Group protocol 062). Antimicrob Agents Chemother. 1995 Dec;39(12):2732-7. doi: 10.1128/AAC.39.12.2732.
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A Study of Zidovudine in HIV-Infected Patients With Liver Disease

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