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A Study of Zidovudine in HIV-Infected Patients With Kidney Problems

Primary Purpose

HIV Infections, Kidney Disease

Status
Withdrawn
Phase
Phase 1
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 Kidney Diseases, Drug Evaluation, Acquired Immunodeficiency Syndrome, Zidovudine, Renal Dialysis

Eligibility Criteria

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

Inclusion Criteria Concurrent Medication: Allowed: Symptomatic therapy such as analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy. Aerosolized pentamidine. Discouraged: - Sucralfate or antacids. However if these medications are essential for the patient's management, they should not be given within 8 hours before or 2 hours after the scheduled pharmacokinetic study. - Concurrent Treatment: Allowed: Blood transfusions. Patients must have HIV infection with renal insufficiency and acceptable hepatic and hematologic function. They must have been on dialysis treatment for at least 3 months. Prior Medication: Allowed: Cytotoxic chemotherapy for local mucocutaneous lesions. Aerosolized pentamidine. Exclusion Criteria Concurrent Medication: Excluded: Ongoing therapy for opportunistic infections, including systemic maintenance therapy which cannot be discontinued for the duration of the study, such as amphotericin B or ganciclovir. H-2 blockers. Zidovudine (AZT). Other antiretroviral agents or other experimental therapy. Discouraged: - Sucralfate or antacids. However, if these medications are essential for the patient's management, they should not be given within 8 hours before or 2 hours after the scheduled pharmacokinetic study. - Patients will be excluded from the study for the following reasons: Presence of active opportunistic infections. Severe malabsorption syndrome (persistent diarrhea greater than 4 weeks duration with = or > 4 loose stools per day accompanied by = or > 10 percent unintentional weight loss. Acute illness, febrile or unstable, 48 hours prior to the first pharmacokinetic study. Known sensitivity to zidovudine or thymidine-type agents. Diabetes mellitus requiring treatment. Prior Medication: Excluded: - Treatment for diabetes mellitus. Excluded within 72 hours of study entry: H-2 blockers. Zidovudine (AZT). Excluded within 2 weeks of study entry: Other antiretroviral agents or other experimental therapy. Rifampin or rifampin derivatives. Probenecid. Dilantin. Methadone. Oral contraceptives. Barbiturates. Significant hepatotoxic agents or valproic acid. TMP / SMX. Dapsone. Fansidar. Excluded within 30 days of study entry: - Cytotoxic chemotherapy. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy for local mucocutaneous lesions. Risk Behavior: Active drug or alcohol use which might interfere with the study objectives. Note: Alcohol consumption is prohibited 48 hours prior to the first pharmacokinetic study and during the study. Tobacco smoking is not excluded although tobacco use will be quantified. Patients may not have any of the following diseases or symptoms: Presence of active opportunistic infections. Severe malabsorption syndrome (persistent diarrhea greater than 4 weeks duration with = or > 4 loose stools per day accompanied by = or > 10 percent unintentional weight loss. Acute illness, febrile or unstable, 48 hours prior to the first pharmacokinetic study. Diabetes mellitus.

Sites / Locations

  • Univ of North Carolina
  • Univ of Washington

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000685
Brief Title
A Study of Zidovudine in HIV-Infected Patients With Kidney Problems
Official Title
Evaluation of Zidovudine Pharmacokinetics in Patients With Human Immunodeficiency Virus and Varying Degrees of Renal Insufficiency
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Withdrawn
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
February 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 determine how zidovudine (AZT) for the treatment of HIV infection is metabolized and excreted or eliminated in patients with infected or diseased kidneys. To determine the influence of hemodialysis and establish dose guidelines. AZT is the only antiviral agent with demonstrated effectiveness in patients with severe HIV infection. Persons with HIV infection may have additional health problems, one of which is a diseased kidney due to infection of the kidney, or side effects of therapy. The benefits and risks of AZT in patients with diseased kidneys are unknown. It is hoped that this study will allow further understanding of the metabolism and excretion of AZT in patients with kidney disease. AZT pharmacokinetics will be studied in patients with mild, moderate, and severe renal disorders
Detailed Description
AZT is the only antiviral agent with demonstrated effectiveness in patients with severe HIV infection. Persons with HIV infection may have additional health problems, one of which is a diseased kidney due to infection of the kidney, or side effects of therapy. The benefits and risks of AZT in patients with diseased kidneys are unknown. It is hoped that this study will allow further understanding of the metabolism and excretion of AZT in patients with kidney disease. AZT pharmacokinetics will be studied in patients with mild, moderate, and severe renal disorders. Patients receive AZT by mouth on the first day. After taking the AZT, blood samples are taken from a catheter and several urine samples are collected over a 24-hour period. During this time, patients remain in the hospital for the 24 hours or may choose to go home 12 hours after taking the AZT dose and return for the last blood sample the next morning. Following study day 1, patients receive AZT every 4 hours, including in the middle of the night, and keep a diary of the times they take AZT, as well as of the use of other medications, tobacco, or alcohol. A return appointment is made for 8-15 days later. On that day, patients again receive AZT by mouth, and blood tests and urine samples are again taken. Patients who are receiving hemodialysis participate in 1 additional day of pharmacokinetic studies to be arranged during one hemodialysis session. Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) are studied separately and do not participate in the procedures for the other groups. AZT is given as a single oral dose at the beginning of the first morning exchange followed by a pharmacokinetic study. Chronic AZT dosing is initiated following the first exchange. After a minimum of 7 days of AZT therapy and a maximum of 14 days the last dose of AZT is administered and a repeat pharmacokinetic study is done. All patients are seen again 1-2 weeks after completing the last pharmacokinetic study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Kidney Disease
Keywords
Kidney Diseases, Drug Evaluation, Acquired Immunodeficiency Syndrome, Zidovudine, Renal Dialysis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Masking
None (Open Label)
Enrollment
0 (Actual)

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: Symptomatic therapy such as analgesics, antihistamines, antiemetics, antidiarrheal agents, or other supportive therapy. Aerosolized pentamidine. Discouraged: - Sucralfate or antacids. However if these medications are essential for the patient's management, they should not be given within 8 hours before or 2 hours after the scheduled pharmacokinetic study. - Concurrent Treatment: Allowed: Blood transfusions. Patients must have HIV infection with renal insufficiency and acceptable hepatic and hematologic function. They must have been on dialysis treatment for at least 3 months. Prior Medication: Allowed: Cytotoxic chemotherapy for local mucocutaneous lesions. Aerosolized pentamidine. Exclusion Criteria Concurrent Medication: Excluded: Ongoing therapy for opportunistic infections, including systemic maintenance therapy which cannot be discontinued for the duration of the study, such as amphotericin B or ganciclovir. H-2 blockers. Zidovudine (AZT). Other antiretroviral agents or other experimental therapy. Discouraged: - Sucralfate or antacids. However, if these medications are essential for the patient's management, they should not be given within 8 hours before or 2 hours after the scheduled pharmacokinetic study. - Patients will be excluded from the study for the following reasons: Presence of active opportunistic infections. Severe malabsorption syndrome (persistent diarrhea greater than 4 weeks duration with = or > 4 loose stools per day accompanied by = or > 10 percent unintentional weight loss. Acute illness, febrile or unstable, 48 hours prior to the first pharmacokinetic study. Known sensitivity to zidovudine or thymidine-type agents. Diabetes mellitus requiring treatment. Prior Medication: Excluded: - Treatment for diabetes mellitus. Excluded within 72 hours of study entry: H-2 blockers. Zidovudine (AZT). Excluded within 2 weeks of study entry: Other antiretroviral agents or other experimental therapy. Rifampin or rifampin derivatives. Probenecid. Dilantin. Methadone. Oral contraceptives. Barbiturates. Significant hepatotoxic agents or valproic acid. TMP / SMX. Dapsone. Fansidar. Excluded within 30 days of study entry: - Cytotoxic chemotherapy. Prior Treatment: Excluded within 30 days of study entry: Radiation therapy for local mucocutaneous lesions. Risk Behavior: Active drug or alcohol use which might interfere with the study objectives. Note: Alcohol consumption is prohibited 48 hours prior to the first pharmacokinetic study and during the study. Tobacco smoking is not excluded although tobacco use will be quantified. Patients may not have any of the following diseases or symptoms: Presence of active opportunistic infections. Severe malabsorption syndrome (persistent diarrhea greater than 4 weeks duration with = or > 4 loose stools per day accompanied by = or > 10 percent unintentional weight loss. Acute illness, febrile or unstable, 48 hours prior to the first pharmacokinetic study. Diabetes mellitus.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tartaglione TA
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
275997215
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
2293640
Citation
Tartaglione TA, Holeman E, Opheim K, Smith T, Collier AC. Zidovudine disposition during hemodialysis in a patient with acquired immunodeficiency syndrome. J Acquir Immune Defic Syndr (1988). 1990;3(1):32-4.
Results Reference
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A Study of Zidovudine in HIV-Infected Patients With Kidney Problems

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