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

Further Study Details: 

Expected Total Enrollment:  150

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.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

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.

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

Study chairs or principal investigators

BJ Luft,  Study Chair
JL Vilde,  Study Chair

Study ID Numbers:  ACTG 154
Record last reviewed:  December 1994
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000643
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08