NCT00000674

Brief Summary

To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.

Trial Health

80
On Track

Trial Health Score

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

Enrollment
30

participants targeted

Target at below P25 for not_applicable

Geographic Reach
1 country

13 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

August 1, 1992

Completed
7.3 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

May 18, 2012

Status Verified

May 1, 2012

First QC Date

November 2, 1999

Last Update Submit

May 17, 2012

Conditions

Toxoplasmosis, CerebralHIV Infections

Keywords

ToxoplasmosisAIDS-Related Opportunistic InfectionsPyrimethamineLeucovorinDrug EvaluationDrug Therapy, CombinationEncephalitisAcquired Immunodeficiency SyndromeClindamycin

Interventions

PyrimethamineDRUG
Leucovorin calciumDRUG
ClindamycinDRUG

Eligibility Criteria

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

You may qualify if:

  • Concurrent Medication:
  • Allowed:
  • Erythropoietin.
  • Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).
  • Immunoglobulin therapy.
  • Alpha interferon.
  • Patients entering study on isoniazid (INH) may continue INH therapy.
  • Use of corticosteroids is discouraged. If corticosteroids are needed for the management of intracranial hypertension or cranial mass effect, use of dexamethasone is encouraged (4 g orally 4 times daily for 3 days and thereafter tapered over the next 10 to 14 days).
  • Patients are admitted into the study if they have:
  • Laboratory evidence of HIV infection or if they have an undetermined HIV infection status if they belong to a high-risk group for HIV infection.
  • Either a definite or presumptive diagnosis of toxoplasmic encephalitis. Patient or appropriate family member, or legal designee must be able to understand and sign a written informed consent.
  • Allowed:
  • HIV encephalopathy.
  • AMENDED:
  • Allows patients who have relapsed. Patients with a previous diagnosis of toxoplasmic encephalitis based on histopathology or documented neuroradiological response to pyrimethamine and sulfonamides or pyrimethamine and clindamycin and who have relapsed toxoplasmic encephalitis. Relapse must be documented by definite progression of lesions or appearance of new lesions compatible with toxoplasmic encephalitis.
  • +4 more criteria

You may not qualify if:

  • Co-existing Condition:
  • Patients with the following are excluded:
  • Infections of the central nervous system.
  • Malabsorption syndrome (3 or more loose stools a day for at least 4 weeks associated with an unintentional weight loss of at least 10 percent of body weight).
  • History of sensitivity to the study medication.
  • Malignancies requiring the use of cytotoxic chemotherapy.
  • Coma.
  • Diffuse central white matter lesions.
  • Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive).
  • Lymphoma of the central nervous system.
  • Cerebral Kaposi's sarcoma.
  • Hemorrhagic diathesis or active bleeding disorder.
  • Concurrent Medication:
  • Excluded:
  • Erythromycin or other macrolides.
  • +28 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

USC CRS

Los Angeles, California, 90033, United States

Location

Stanford CRS

Palo Alto, California, 94304, United States

Location

Ucsd, Avrc Crs

San Diego, California, 92103, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 33136, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14215, 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

Unc Aids Crs

Chapel Hill, North Carolina, 27599, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

Pitt CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

  • Luft BJ, Hafner R, Korzun AH, Leport C, Antoniskis D, Bosler EM, Bourland DD 3rd, Uttamchandani R, Fuhrer J, Jacobson J, et al. Toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome. Members of the ACTG 077p/ANRS 009 Study Team. N Engl J Med. 1993 Sep 30;329(14):995-1000. doi: 10.1056/NEJM199309303291403.

    PMID: 8366923BACKGROUND

MeSH Terms

Conditions

Toxoplasmosis, CerebralHIV InfectionsToxoplasmosisAIDS-Related Opportunistic InfectionsEncephalitisAcquired Immunodeficiency Syndrome

Interventions

PyrimethamineLeucovorinClindamycin

Condition Hierarchy (Ancestors)

Brain AbscessCentral Nervous System InfectionsInfectionsCentral Nervous System Protozoal InfectionsCentral Nervous System Parasitic InfectionsParasitic DiseasesCoccidiosisProtozoan 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 DiseasesOpportunistic InfectionsNeuroinflammatory DiseasesSlow Virus Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Remington JS

    STUDY CHAIR

  • Luft B

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
not applicable
Masking
NONE
Purpose
TREATMENT
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 2, 1999

First Posted

August 31, 2001

Study Completion

August 1, 1992

Last Updated

May 18, 2012

Record last verified: 2012-05

Locations

US(13)