NCT00000643

Brief Summary

To evaluate the effectiveness of pyrimethamine (given with leucovorin calcium versus placebo (an inactive substance) for the primary prophylaxis (prevention) of cerebral toxoplasmosis in HIV-infected patients. Cerebral toxoplasmosis is one of the most frequently encountered opportunistic infections in the course of AIDS. The mortality (death) rate is estimated to be greater than 50 percent. Pyrimethamine is a drug that appears promising for the primary prevention of cerebral toxoplasmosis in HIV-infected patients.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P75+ for phase_2

Geographic Reach
1 country

24 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Completion

Last participant's last visit for all outcomes

May 1, 1994

Completed
5.5 years until next milestone

First Submitted

Initial submission to the registry

November 2, 1999

Completed
1.8 years until next milestone

First Posted

Study publicly available on registry

August 31, 2001

Completed
Last Updated

November 2, 2021

Status Verified

October 1, 2021

First QC Date

November 2, 1999

Last Update Submit

October 26, 2021

Conditions

Keywords

ToxoplasmosisPyrimethamineLeucovorinDrug EvaluationAcquired Immunodeficiency SyndromeAIDS-Related ComplexBrain Diseases

Interventions

Eligibility Criteria

Age13 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Concurrent Medication:
  • Allowed:
  • Zidovudine (AZT), didanosine (ddI), dideoxycytidine (ddC), erythropoietin (Eprex), other agents granted Treatment IND or expanded access status.
  • Investigational triazoles.
  • Pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia (PCP).
  • Patients with the following are excluded:
  • History of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue.
  • Focal neural abnormalities (except peripheral neuropathy) or mass lesions on a previous computerized tomography (CT) scan or magnetic resonance image (MRI), unless subsequent workup rules out toxoplasmosis, in which case abnormalities must have been stable for at least 2 months.
  • Known or suspected allergy or severe intolerance to study drugs.
  • Patients must have:
  • Positive toxoplasma serology.
  • HIV infection.
  • Willingness and ability to comply with the protocol and capability of giving written informed consent.

You may not qualify if:

  • Co-existing Condition:
  • Patients with the following conditions or symptoms are excluded:
  • Current diagnosis of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue.
  • Known or suspected allergy or severe intolerance to study drugs.
  • Concurrent Medication:
  • Excluded:
  • Anticoagulants. Other antifolates, sulfonamides, fansidar, macrolides, 5-fluorouracil, dapsone, or any other agent with known activity against Toxoplasma gondii.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (24)

Stanford CRS

Palo Alto, California, 94304, United States

Location

Harbor-UCLA Med. Ctr. CRS

Torrance, California, 90502, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 33136, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, 60611, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202, United States

Location

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU

New Orleans, Louisiana, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Bmc Actg Crs

Boston, Massachusetts, 02118, United States

Location

University of Minnesota, ACTU

Minneapolis, Minnesota, 55455, United States

Location

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

NJ Med. School CRS

Newark, New Jersey, 07103, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14215, United States

Location

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, 10003, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Cornell University A2201

New York, New York, 10021, United States

Location

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, 10021, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27599, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 45267, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

Pitt CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (7)

  • Rousseau F, Pueyo S, Morlat P, Hafner R, Chene G, Leport C, Luft BJ, Miro J, Aubertin J, Salamon R, Vilde JL. Increased risk of toxoplasmic encephalitis in human immunodeficiency virus-infected patients with pyrimethamine-related rash. ANRS 005-ACTG 154 Trial Group. Agence Nationale de Recherche sur le SIDA (ANRS-INSERM) and the NIAID-AIDS Clinical Trials Group. Clin Infect Dis. 1997 Mar;24(3):396-402. doi: 10.1093/clinids/24.3.396.

    PMID: 9114191BACKGROUND
  • Leport C, Chene G, Farinotti R, Ecobichon J-L, Petavin G, Sagardoy G, Morlat P, Hafner R, Luft B, Salamon R, Vilde J-L. Determination of pyrimethamine serum levels in a primary prophylaxis trial for toxoplasmic encephalitis. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:159

    BACKGROUND
  • Leport C, Chene G, Morlat P, Luft BJ, Rousseau F, Pueyo S, Hafner R, Miro J, Aubertin J, Salamon R, Vilde JL. Pyrimethamine for primary prophylaxis of toxoplasmic encephalitis in patients with human immunodeficiency virus infection: a double-blind, randomized trial. ANRS 005-ACTG 154 Group Members. Agence Nationale de Recherche sur le SIDA. AIDS Clinical Trial Group. J Infect Dis. 1996 Jan;173(1):91-7. doi: 10.1093/infdis/173.1.91.

    PMID: 8537688BACKGROUND
  • Pueyo S, Salmi LR, Chene G, Leport C, Morlat P, Dequae L, Gregoire V, Hafner R, Vilde JL, Luft BJ, Aubertin J, Salamon R. Survival after AIDS-defining events in patients with < 200 lymphocytes CD4+ x 10(6)/L who are toxoplasmosis antibody positive. ANRS 005/ACTG 154 Trial Group. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Apr 15;14(5):459-64. doi: 10.1097/00042560-199704150-00010.

    PMID: 9170421BACKGROUND
  • Derouin F, Leport C, Pueyo S, Morlat P, Letrillart B, Chene G, Ecobichon JL, Luft B, Aubertin J, Hafner R, Vilde JL, Salamon R. Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group. AIDS. 1996 Nov;10(13):1521-7. doi: 10.1097/00002030-199611000-00010.

    PMID: 8931787BACKGROUND
  • Chene G, Morlat P, Hafner R, Aboulker JP, Luft B, Dormont J, Vilde JL, Salamon R. Intent-to-treat versus on treatment analysis: how to interpret the results of a clinical trial? Experience from ANRS 005/ACTG 154 study. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:100

    BACKGROUND
  • Chene G, Morlat P, Leport C, Hafner R, Dequae L, Charreau I, Aboulker JP, Luft B, Aubertin J, Vilde JL, Salamon R. Intention-to-treat vs. on-treatment analyses of clinical trial data: experience from a study of pyrimethamine in the primary prophylaxis of toxoplasmosis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group. Control Clin Trials. 1998 Jun;19(3):233-48. doi: 10.1016/s0197-2456(97)00145-1.

    PMID: 9620807BACKGROUND

MeSH Terms

Conditions

Toxoplasmosis, CerebralHIV InfectionsToxoplasmosisAcquired Immunodeficiency SyndromeAIDS-Related ComplexBrain Diseases

Interventions

PyrimethamineLeucovorin

Condition Hierarchy (Ancestors)

Brain AbscessCentral Nervous System InfectionsInfectionsCentral Nervous System Protozoal InfectionsCentral Nervous System Parasitic InfectionsParasitic DiseasesCoccidiosisProtozoan InfectionsAbscessSuppurationCentral Nervous System DiseasesNervous System DiseasesBlood-Borne InfectionsCommunicable DiseasesSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System DiseasesSlow Virus Diseases

Intervention Hierarchy (Ancestors)

PyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and Coenzymes

Study Officials

  • BJ Luft

    STUDY CHAIR
  • JL Vilde

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Masking
DOUBLE
Purpose
PREVENTION
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Study Completion

May 1, 1994

Last Updated

November 2, 2021

Record last verified: 2021-10

Locations