NCT00000794

Brief Summary

To evaluate the efficacy, safety, and tolerance of atovaquone with either pyrimethamine or sulfadiazine in AIDS patients with toxoplasmic encephalitis. AIDS patients with toxoplasmic encephalitis who receive the standard therapy combination of sulfadiazine and pyrimethamine experience a high frequency of severe toxicity. Atovaquone, an antibiotic that has demonstrated efficacy against toxoplasmosis in animal models and in preclinical testing has been well tolerated, is now available as a suspension, which is more readily absorbed than the tablet form of the drug. The efficacy and safety of atovaquone in combination with sulfadiazine or pyrimethamine will be studied.

Trial Health

80
On Track

Trial Health Score

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

Enrollment
100

participants targeted

Target at P50-P75 for phase_2

Geographic Reach
1 country

16 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

April 1, 1998

Completed
1.6 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

October 28, 2021

Status Verified

October 1, 2021

First QC Date

November 2, 1999

Last Update Submit

October 27, 2021

Conditions

Keywords

PyrimethamineLeucovorinDrug Therapy, CombinationEncephalitisAcquired Immunodeficiency SyndromeAntiprotozoal AgentsClarithromycinatovaquoneToxoplasmosis, CerebralSulfadiazine

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:
  • Aerosolized pentamidine for PCP prophylaxis.
  • PER AMENDMENT 4/3/96:
  • History of treatment limiting toxicity to pyrimethamine. Patients with a history of treatment limiting toxicity to both pyrimethamine and sulfonamides will be assigned to receive atovaquone plus clarithromycin.
  • Patients must have:
  • Documented HIV infection or diagnosis of AIDS (except for CD4 count \< 200 cells/mm3).
  • Toxoplasmic encephalitis.
  • Ability to give informed consent or legal designee who could give consent.
  • PER AMENDMENT 4/3/96:
  • NOTE - A history of treatment limiting toxicity to both pyrimethamine and sulfonamides will result in the patient being enrolled in the atovaquone plus clarithromycin arm.

You may not qualify if:

  • Co-existing Condition:
  • Patients with the following symptoms or conditions are excluded:
  • Coma.
  • Opportunistic infection that requires either acute or maintenance treatment with disallowed medications.
  • Any infections or neoplasms of the central nervous system other than Toxoplasma, HIV encephalopathy, or syphilis.
  • Unable to take oral study drugs.
  • Malabsorption (i.e., three or more episodes of diarrhea per day that has caused \>= 10 percent loss of body weight over the past 4 weeks).
  • Positive CSF or serum for Cryptococcus antigen or culture (a positive serum antigen only is acceptable, provided patient received prior antifungal therapy and is on maintenance, and the likelihood of recurrence is low).
  • Malignancy requiring use of cytotoxic chemotherapy.
  • Medical or social condition that would adversely affect study participation or compliance.
  • Concurrent Medication:
  • Excluded:
  • Trimethoprim-sulfamethoxazole.
  • Primaquine.
  • Sulfonamides.
  • +16 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

USC CRS

Los Angeles, California, 900331079, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 331361013, United States

Location

Queens Med. Ctr.

Honolulu, Hawaii, 96816, United States

Location

Univ. of Hawaii at Manoa, Leahi Hosp.

Honolulu, Hawaii, 96816, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Cook County Hosp. CORE Ctr.

Chicago, Illinois, 60612, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 462025250, United States

Location

Methodist Hosp. of Indiana

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Washington U CRS

St Louis, Missouri, 63110, United States

Location

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 13210, 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, United States

Location

Univ. of Cincinnati CRS

Cincinnati, Ohio, 452670405, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 432101228, United States

Location

Related Publications (1)

  • Chirgwin K, Hafner R, Leport C, Remington J, Andersen J, Bosler EM, Roque C, Rajicic N, McAuliffe V, Morlat P, Jayaweera DT, Vilde JL, Luft BJ. Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039. Clin Infect Dis. 2002 May 1;34(9):1243-50. doi: 10.1086/339551.

    PMID: 11941551BACKGROUND

MeSH Terms

Conditions

Toxoplasmosis, CerebralHIV InfectionsEncephalitisAcquired Immunodeficiency Syndrome

Interventions

SulfadiazineClarithromycinAtovaquonePyrimethamineLeucovorin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

BenzenesulfonamidesSulfonamidesAmidesOrganic ChemicalsSulfanilamidesAniline CompoundsAminesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsSulfonesSulfur CompoundsErythromycinMacrolidesPolyketidesLactonesNaphthoquinonesQuinonesNaphthalenesPolycyclic Aromatic HydrocarbonsPolycyclic CompoundsPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and Coenzymes

Study Officials

  • Luft B

    STUDY CHAIR
  • Chirgwin K

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Study Completion

April 1, 1998

Last Updated

October 28, 2021

Record last verified: 2021-10

Locations