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Evaluation of the Interaction Between Low Dose Sulfamethoxazole-Trimethoprim and Zidovudine

Primary Purpose

HIV Infections

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Sulfamethoxazole-Trimethoprim
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 Trimethoprim-Sulfamethoxazole Combination, Pneumonia, Pneumocystis carinii, Drug Interactions, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine, Sulfamethoxazole-Trimethoprim

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria Prior Medication: Allowed: Zidovudine (AZT) for patients with AIDS. AIDS related complex (ARC). The presence of any one of the following findings within 12 months prior to entry and the absence of a concurrent illness or conditions other than HIV infection to explain the findings: Fever of > 38.5 C degrees persisting for longer than 3 weeks. Involuntary weight loss of > 15 lbs. or > 10 percent of baseline noted in a 120-day period prior to evaluation. Diarrhea (> 2 liquid stools per day) persisting for longer than 1 month. History of clinical diagnosis of oral candidiasis or hairy leukoplakia. Patients who have AIDS-defining opportunistic infections or tumors. Patients eligible for AZT under the labeling. A positive HIV antibody test. Exceptions will be made for patients with a previously positive HIV antibody test with progressive disease and patients where virus isolation has been made. A life expectancy of at least 3 months. Patient with stable Kaposi's sarcoma, mild herpes infection, mild or stable depression, asymptomatic or mild cytomegalovirus or Epstein-Barr virus infection, or a hepatitis B virus carrier state will be acceptable for study. Exclusion Criteria Concurrent Medication: Excluded: Phenytoin. Prior Medication: Excluded within 30 days of study entry: Other antiretroviral agents. Patient has any severe ongoing opportunistic infections including Pneumocystis carinii pneumonia (PCP), cryptococcal or toxoplasmosis meningoencephalitis, disseminated herpes simplex or herpes zoster. Patient has significant diarrhea at entry ( > 1 watery stool per day). Patient has demonstrated prior sensitivity or has experienced significant adverse effects during prior therapy with the drugs to be used in the study. Cannot abstain from alcohol or any other drugs during the study.

Sites / Locations

  • Univ of Pittsburgh Med School

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 27, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000732
Brief Title
Evaluation of the Interaction Between Low Dose Sulfamethoxazole-Trimethoprim and Zidovudine
Official Title
Evaluation of the Interaction Between Low Dose Trimethoprim/Sulfamethoxazole and Zidovudine
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 determine if the pharmacokinetics of low doses of zidovudine (AZT) (that is, how fast AZT reaches the blood, what concentration of AZT is attained in the blood, and how long AZT remains in the blood) changes from day-to-day in the same patient. Also to determine whether the pharmacokinetics of AZT is changed by sulfamethoxazole/trimethoprim (SMX/TMP) given at the same time or whether the pharmacokinetics of SMX/TMP is altered by AZT therapy. AZT has been effective in treating some patients with AIDS, and SMX/TMP is an antibiotic combination which is useful in preventing or treating Pneumocystis carinii pneumonia (PCP), which is an important cause of disease and death in patients with AIDS. It is important to know how drugs interact in patients because addition of a second drug may change the speed at which a drug is eliminated from the body, and cause increased toxic effects or decreased therapeutic effects.
Detailed Description
AZT has been effective in treating some patients with AIDS, and SMX/TMP is an antibiotic combination which is useful in preventing or treating Pneumocystis carinii pneumonia (PCP), which is an important cause of disease and death in patients with AIDS. It is important to know how drugs interact in patients because addition of a second drug may change the speed at which a drug is eliminated from the body, and cause increased toxic effects or decreased therapeutic effects. Patients take AZT every 4 hours and/or SMX/TMP every 12 hours by mouth for 4 days as outpatients and then come into the clinical research center for 2 days of studies. On day 5 the final dose of medicine is given orally (SMX/TMP) or by intravenous infusion (AZT). Blood samples are drawn 10-20 times over a period of 12 hours and urine is collected for 36 hours. Concentrations of the drugs in the blood and urine samples are determined. This sequence is repeated twice, so that each patient takes AZT alone, SMX/TMP alone, and the combination of AZT and SMX/TMP over a period of about 3 weeks. Patients may be included in the study if they are asymptomatic, or have been diagnosed with ARC or AIDS, but not if they have PCP or any other severe opportunistic infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Trimethoprim-Sulfamethoxazole Combination, Pneumonia, Pneumocystis carinii, Drug Interactions, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine, Sulfamethoxazole-Trimethoprim

7. Study Design

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

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Sulfamethoxazole-Trimethoprim
Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Prior Medication: Allowed: Zidovudine (AZT) for patients with AIDS. AIDS related complex (ARC). The presence of any one of the following findings within 12 months prior to entry and the absence of a concurrent illness or conditions other than HIV infection to explain the findings: Fever of > 38.5 C degrees persisting for longer than 3 weeks. Involuntary weight loss of > 15 lbs. or > 10 percent of baseline noted in a 120-day period prior to evaluation. Diarrhea (> 2 liquid stools per day) persisting for longer than 1 month. History of clinical diagnosis of oral candidiasis or hairy leukoplakia. Patients who have AIDS-defining opportunistic infections or tumors. Patients eligible for AZT under the labeling. A positive HIV antibody test. Exceptions will be made for patients with a previously positive HIV antibody test with progressive disease and patients where virus isolation has been made. A life expectancy of at least 3 months. Patient with stable Kaposi's sarcoma, mild herpes infection, mild or stable depression, asymptomatic or mild cytomegalovirus or Epstein-Barr virus infection, or a hepatitis B virus carrier state will be acceptable for study. Exclusion Criteria Concurrent Medication: Excluded: Phenytoin. Prior Medication: Excluded within 30 days of study entry: Other antiretroviral agents. Patient has any severe ongoing opportunistic infections including Pneumocystis carinii pneumonia (PCP), cryptococcal or toxoplasmosis meningoencephalitis, disseminated herpes simplex or herpes zoster. Patient has significant diarrhea at entry ( > 1 watery stool per day). Patient has demonstrated prior sensitivity or has experienced significant adverse effects during prior therapy with the drugs to be used in the study. Cannot abstain from alcohol or any other drugs during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ptachcinski R
Official's Role
Study Chair
Facility Information:
Facility Name
Univ of Pittsburgh Med School
City
Pittsburgh
State/Province
Pennsylvania
Country
United States

12. IPD Sharing Statement

Citations:
Citation
Berson A, Happy K, Rousseau F, Grateau G, Farinotti R, Sereni D. Effect of zidovudine (AZT) on cotrimoxazole (TMP-SMX) kinetics: preliminary results. Int Conf AIDS. 1993 Jun 6-11;9(1):501 (abstract no PO-B30-2193)
Results Reference
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PubMed Identifier
8787912
Citation
Canas E, Pachon J, Garcia-Pesquera F, Castillo JR, Viciana P, Cisneros JM, Jimenez-Mejias ME. Absence of effect of trimethoprim-sulfamethoxazole on pharmacokinetics of zidovudine in patients infected with human immunodeficiency virus. Antimicrob Agents Chemother. 1996 Jan;40(1):230-3. doi: 10.1128/AAC.40.1.230.
Results Reference
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Evaluation of the Interaction Between Low Dose Sulfamethoxazole-Trimethoprim and Zidovudine

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