skip to content

Clinical Trials

MainTitle

A Study of Pyrimethamine in the Treatment of Infection by a Certain Parasite in HIV-Positive Patients

This study has been completed
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator
Glaxo Wellcome

Information provided by (Responsible Party)
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier
NCT00000973

First received: November 2, 1999
Last updated: March 29, 2012
Last Verified: March 2012
History of Changes
Purpose

Purpose

To determine the manner in which pyrimethamine is metabolized and excreted in patients currently receiving zidovudine (AZT). An important goal of this measurement is to establish the optimal dose of pyrimethamine necessary to prevent the development of toxoplasmosis in AIDS patients or delay the subsequent return of toxoplasmic encephalitis.

Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. The best treatment for this disease has not been determined. Presently it is standard practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there are reports that patients already exposed to toxoplasmosis may not have uniform absorption of pyrimethamine.

Condition Intervention Phase
Toxoplasmosis, Cerebral
HIV Infections

Drug : Pyrimethamine
Drug : Leucovorin calcium
Drug : Zidovudine
Phase 1

Study Type: Interventional
Study Design: Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pyrimethamine Pharmacokinetics in HIV Positive Patients Seropositive for Toxoplasma Gondii

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

Enrollment: 26
Study Completion Date: March 1995

Detailed Description:

Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. The best treatment for this disease has not been determined. Presently it is standard practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there are reports that patients already exposed to toxoplasmosis may not have uniform absorption of pyrimethamine.
Patients receive the study treatment for a total of 22 days. Patients are given an initial dose of pyrimethamine followed by a lower dose given as a single oral daily dose for 21 days. Patients continue to receive AZT at the dose prescribed prior to enrollment in the study. Patients receive leucovorin calcium once a day. Neither the leucovorin calcium nor the AZT are provided through the study.

Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

Inclusion Criteria
Concurrent Medication:
Allowed:

  • Aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis.
  • Isoniazid not initiated during study period.
  • Methadone maintenance.

  • Required:
  • Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day.

  • Exclusion Criteria
    Co-existing Condition:
    Patients with the following conditions or symptoms are excluded:
  • Prior history of toxoplasmic encephalitis.
  • Unable to take oral medication reliably or have a malabsorption syndrome (i.e., 3 or more loose stools/day for at least 4 weeks associated with an unintentional weight loss of = or > 10 percent of body weight).
  • History of sensitivity to the study medications.

  • Concurrent Medication:
    Excluded:
  • Maintenance therapy for opportunistic infections with macrolides or sulfonamides, immunomodulators, rifampin, amphotericin, dapsone, ganciclovir, antifolates, probenecid, benzodiazepines, nephrotoxins, and experimental cytotoxic chemotherapy.
  • Medications such as aspirin, benzodiazepines, cimetidine, indomethacin, morphine, and sulfonamides should be avoided.

  • Concurrent Treatment:
    Excluded:
  • Lymphocyte replacement.

  • Patients with the following are excluded:
  • Any medical or social condition that, in the opinion of the investigator, would adversely affect either participation or compliance in the study.
  • Diagnosis of AIDS and febrile and have evidence of another serious opportunistic infection or central nervous system impairment.

  • Prior Medication:
    Excluded:
  • Maintenance therapy for opportunistic infections with macrolides or sulfonamides, immunomodulators, rifampin, amphotericin, dapsone, ganciclovir, antifolates, probenecid, benzodiazepines, nephrotoxins, and experimental cytotoxic chemotherapy within past 14 days.

  • Prior Treatment:
    Excluded:
  • Lymphocyte replacement within past 14 days.

  • Patients have the following symptoms and conditions:
  • Laboratory evidence of HIV infection.
  • Serological evidence of exposure to Toxoplasma gondii, but no clinical evidence of active toxoplasmic infection.
  • Able to understand and sign a written informed consent.
  • Either homosexual male or intravenous drug user.

  • Required:
  • Stable prescribed dose of zidovudine (AZT) of at least 500 mg/day for 4 weeks.
Intravenous drug abuse.

contacts and locations

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: NCT00000973

Locations

United States, New York
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Glaxo Wellcome

Investigators

Study Chair: B Luft
More Information

More Information


Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)  
ClinicalTrials.gov Identifier: NCT00000973   History of Changes  
Other Study ID Numbers: ACTG 102  
  11077  
Study First Received: November 2, 1999  
Last Updated: March 29, 2012  

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Toxoplasmosis
Toxoplasma
Pyrimethamine
Leucovorin
Drug Evaluation
Encephalitis
Zidovudine

Additional relevant MeSH terms:
Infection
HIV Infections
Toxoplasmosis
Toxoplasmosis, Cerebral
Zidovudine
Pyrimethamine
Levoleucovorin

ClinicalTrials.gov processed this data on October 17, 2017
This information is provided by ClinicalTrials.gov.