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.

Condition	Treatment or Intervention
Toxoplasmosis, Cerebral HIV Infections	Drug: Pyrimethamine  Drug: Leucovorin calcium  Drug: Clindamycin

Further Study Details: 

Expected Total Enrollment:  30

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.

Amended: Projected accrual increased to 50 patients. Original design: Patients receive study medications for a total of 6 weeks unless there are intervening events that require the discontinuation of study therapy. Patients are initially treated in the hospital (minimum of 7 days). Patients who are considered responders at day 7 may complete therapy on an outpatient basis. Nonresponders at day 7 may also be managed on an outpatient basis when it is medically appropriate.

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

Criteria

Inclusion Criteria

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.

Prior Medication: Allowed if liver enzymes stable for 6 weeks prior to study entry:

• Rifampin.
• Isoniazid.

Exclusion Criteria

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.
• Sulfonamides.
• Immunomodulators.
• Cytotoxic chemotherapy.
• Amphotericin.
• Dapsone.
• Rifamycins.
• Ganciclovir.
• Allopurinol.
• Antifolates.
• Azidothymidine and other antiretrovirals and investigational agents not specifically allowed.
• Folate supplements.
• Isoniazid (INH) therapy may not be started while on therapy.

Concurrent Treatment: Excluded:

• Lymphocyte replacement.

Patients with the following are excluded:

• Negative HIV antibodies by a federally licensed ELISA (as determined at or after study entry), unless there is documentation of a previously positive HIV culture or p24 antigen.
• 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.
• Unable to take oral medications reliably.
• Any medical or social condition which, in the opinion of the investigator, would adversely affect either participation and/or compliance in this study.

Prior Medication: Excluded:

• Treatment for toxoplasmic encephalitis.

California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      Stanford at Kaiser / Kaiser Permanente Med Ctr, San Francisco,  California,  94115,  United States
      Stanford Univ Med Ctr, Stanford,  California,  943055107,  United States
      Palo Alto Veterans Adm Med Ctr / Stanford Univ, Palo Alto,  California,  94304,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
Florida
      Univ of Miami School of Medicine, Miami,  Florida,  331361013,  United States
Illinois
      Northwestern Univ Med School, Chicago,  Illinois,  60611,  United States
Louisiana
      Charity Hosp / Tulane Univ Med School, New Orleans,  Louisiana,  70112,  United States
      Louisiana State Univ Med Ctr / Tulane Med School, New Orleans,  Louisiana,  70112,  United States
      Tulane Univ School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maryland
      Johns Hopkins Hosp, Baltimore,  Maryland,  21287,  United States
Massachusetts
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
      Univ of Massachusetts Med Ctr, Worcester,  Massachusetts,  01655,  United States
New York
      SUNY - Stony Brook, Stony Brook,  New York,  117948153,  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
      Mount Sinai Med Ctr, New York,  New York,  10029,  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
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
Pennsylvania
      Univ of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
      Presbyterian Univ Hosp / Univ of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States

Study chairs or principal investigators

Remington JS,  Study Chair
Luft B,  Study Chair

Study ID Numbers:  ACTG 077 PILOT
Record last reviewed:  August 1992
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000674
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08