Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000643

Purpose

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.

Condition	Intervention	Phase
Toxoplasmosis, Cerebral HIV Infections	Drug: Pyrimethamine Drug: Leucovorin calcium	Phase II

Study Type:	Interventional
Study Design:	Prevention, Double-Blind
Official Title:	Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

Resource links provided by NLM:

MedlinePlus related topics: AIDS Brain Diseases Calcium Toxoplasmosis

Drug Information available for: Leucovorin Pyrimethamine Citrovorum factor Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

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

Estimated Enrollment:

150

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000643

Hide Study Locations

Locations

United States, California
Stanford at Kaiser / Kaiser Permanente Med Ctr
San Francisco, California, United States, 94115
Palo Alto Veterans Adm Med Ctr / Stanford Univ
Palo Alto, California, United States, 94304
Harbor UCLA Med Ctr
Torrance, California, United States, 90502
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Illinois
Children's Mem Hosp Family Cln / Northwestern Univ Med Schl
Chicago, Illinois, United States, 60611
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana Univ Hosp
Indianapolis, Indiana, United States, 462025250
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston Med Ctr
Boston, Massachusetts, United States, 02118
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, United States, 01655
United States, Minnesota
Univ of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St Louis Regional Hosp / St Louis Regional Med Ctr
St. Louis, Missouri, United States, 63112
United States, New Jersey
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States, 071032714
United States, New York
SUNY / State Univ of New York
Syracuse, New York, United States, 13210
Montefiore Family Health Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Samaritan Village Inc / Bronx Municipal Hosp
Bronx, New York, United States, 10461
Nassau County Med Ctr
East Meadow, New York, United States, 11554
Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10461
SUNY - Stony Brook
Stony Brook, New York, United States, 117948153
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
Mem Sloan - Kettering Cancer Ctr
New York, New York, United States, 10021
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Jack Weiler Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10465
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
Saint Luke's - Roosevelt Hosp Ctr
New York, New York, United States, 10025
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Cornell Univ Med Ctr
New York, New York, United States, 10021
SUNY / Erie County Med Ctr at Buffalo
Buffalo, New York, United States, 14215
Beth Israel Med Ctr
New York, New York, United States, 10003
City Hosp Ctr at Elmhurst / Mount Sinai Hosp
Elmhurst, New York, United States, 11373
North Central Bronx Hosp / Bronx Municipal Hosp
Bronx, New York, United States, 10467
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Ohio
Case Western Reserve Univ
Cleveland, Ohio, United States, 44106
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Pennsylvania
Univ of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	BJ Luft
Study Chair:	JL Vilde

More Information

Publications:

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.

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

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.

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.

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.

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

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.

Study ID Numbers:	ACTG 154
Study First Received:	November 2, 1999
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00000643 History of Changes
Health Authority:	United States: Federal Government

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

Toxoplasmosis
Pyrimethamine
Leucovorin
Drug Evaluation

Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Brain Diseases

Additional relevant MeSH terms:

Pyrimethamine
Anti-Infective Agents
Antiprotozoal Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Toxoplasmosis, Cerebral
Physiological Effects of Drugs
Leucovorin
Infection
Brain Diseases
Central Nervous System Parasitic Infections
Antimalarials
Antiparasitic Agents
Therapeutic Uses

Vitamins
Suppuration
Parasitic Diseases
Micronutrients
Retroviridae Infections
Protozoan Infections
RNA Virus Infections
Vitamin B Complex
Immune System Diseases
Coccidiosis
Growth Substances
Acquired Immunodeficiency Syndrome
Nervous System Diseases
Brain Abscess
Central Nervous System Diseases

ClinicalTrials.gov processed this record on November 27, 2009