Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

NCT ID: NCT00000643

Last Updated: 2021-11-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1994-05-31

Brief Summary

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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.

Detailed Description

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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.

AMENDED: 04-04-91 On the first day of therapy, a loading dose is given. After the first day, patients take pyrimethamine or placebo 3 times a week. Patients also take leucovorin calcium orally three times weekly. Enrollment occurs over approximately 12 months. All patients are followed on study until a common study close-out date and final analysis of the study. It is anticipated that this common close-out will occur when the mean duration of time on study therapy will be 3 years (approximately in January, 1994).

ORIGINAL design: On the first day of treatment, patients receive a loading dose of pyrimethamine or placebo, plus of leucovorin calcium. After the first day, patients take pyrimethamine or placebo three times a week. Patients also take folinic acid orally three times weekly. The mean duration of study participation is 3 years.

Conditions

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Toxoplasmosis, Cerebral HIV Infections

Keywords

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Toxoplasmosis Pyrimethamine Leucovorin Drug Evaluation Acquired Immunodeficiency Syndrome AIDS-Related Complex Brain Diseases

Study Design

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Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Interventions

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Pyrimethamine

Intervention Type DRUG

Leucovorin calcium

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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.

Exclusion Criteria

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.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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BJ Luft

Role: STUDY_CHAIR

JL Vilde

Role: STUDY_CHAIR

Locations

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Stanford CRS

Palo Alto, California, United States

Site Status

Harbor-UCLA Med. Ctr. CRS

Torrance, California, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Northwestern University CRS

Chicago, Illinois, United States

Site Status

Rush Univ. Med. Ctr. ACTG CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

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

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

Bmc Actg Crs

Boston, Massachusetts, United States

Site Status

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Site Status

St. Louis ConnectCare, Infectious Diseases Clinic

St Louis, Missouri, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

NJ Med. School CRS

Newark, New Jersey, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

Site Status

NY Univ. HIV/AIDS CRS

New York, New York, United States

Site Status

Cornell University A2201

New York, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Ctr.

New York, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States

Site Status

Univ. of Cincinnati CRS

Cincinnati, Ohio, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

Pitt CRS

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 9114191 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 8537688 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9170421 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8931787 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 9620807 (View on PubMed)

Other Identifiers

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11129

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 154

Identifier Type: -

Identifier Source: org_study_id