A Randomized Prospective Study of Pyrimethamine Therapy for Prevention of Toxoplasmic Encephalitis in HIV-Infected Individuals With Serologic Evidence of Latent Toxoplasma Gondii Infection

A Randomized Prospective Study of Pyrimethamine Therapy for Prevention of Toxoplasmic Encephalitis in HIV-Infected Individuals With Serologic Evidence of Latent Toxoplasma Gondii Infection

Sponsors

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Source National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

To evaluate pyrimethamine as a prophylactic agent against toxoplasmic encephalitis in individuals who are coinfected with HIV and latent Toxoplasma gondii.

Toxoplasmic encephalitis is a major cause of illness and death in AIDS patients. Standard treatment for toxoplasmic encephalitis is to combine pyrimethamine and sulfadiazine. Continuous treatment is necessary to prevent recurrence of the disease, but constant use of pyrimethamine/sulfadiazine is associated with toxicity. Clindamycin has been shown to be effective in treatment of toxoplasmic encephalitis in animal studies. This study evaluates pyrimethamine as a preventive treatment against toxoplasmic encephalitis (per 3/26/91 amendment, clindamycin arm was discontinued).

Detailed Description

Toxoplasmic encephalitis is a major cause of illness and death in AIDS patients. Standard treatment for toxoplasmic encephalitis is to combine pyrimethamine and sulfadiazine. Continuous treatment is necessary to prevent recurrence of the disease, but constant use of pyrimethamine/sulfadiazine is associated with toxicity. Clindamycin has been shown to be effective in treatment of toxoplasmic encephalitis in animal studies. This study evaluates pyrimethamine as a preventive treatment against toxoplasmic encephalitis (per 3/26/91 amendment, clindamycin arm was discontinued).

Patients are randomized to receive pyrimethamine or placebo three times a week. All patients must be on aerosolized pentamidine, trimethoprim / sulfamethoxazole (T/S), or dapsone for Pneumocystis carinii pneumonia prophylaxis. Patients will be evaluated bi-weekly for the first month and every other month thereafter for at least 24 months.

Overall Status Completed
Completion Date March 1992
Phase N/A
Study Type Interventional
Enrollment 600
Condition
Intervention

Intervention Type: Drug

Intervention Name: Pyrimethamine

Eligibility

Criteria:

Inclusion Criteria

Concurrent Medication:

Required:

- Prophylactic treatment for Pneumocystis carinii pneumonia with aerosolized pentamidine, dapsone, or trimethoprim / sulfamethoxazole.

Allowed:

- Most medications not specifically excluded.

Prior Medication:

Allowed:

- Antivirals.

- Antiretrovirals.

Patients:

- Must be HIV positive or have an AIDS-defining illness OR be at known risk for HIV infection and have a CD4 cell count < 200/mm3 and no other known immunosuppressive disease.

- Must have positive titer for Toxoplasma gondii.

- Must be or become a patient of a CPCRA physician.

- May participate in other clinical trials as long as there is no potential activity against Toxoplasma gondii or cross-toxicity among study drugs.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

- History of ocular, pulmonary, or central nervous system (CNS) toxicity.

- CNS lesions.

- Neurologic deficits except peripheral neuropathy.

- Mild, moderate, severe, or end-stage AIDS dementia complex. Grade 3 or higher nausea and/or vomiting.

- Sensitivity to pyrimethamine.

Concurrent Medication:

Excluded:

- On-going therapy with clindamycin, fansidar, methotrexate, trimetrexate, spiramycin, azithromycin, clarithromycin, 566C80, and/or sulfa agents other than anti-PCP agents.

Patients with the following are excluded:

- History of ocular, pulmonary, or central nervous system (CNS) toxicity.

- CNS lesions or history of CNS lesions.

- Neurologic deficits except peripheral neuropathy.

- Mild, moderate, severe, or end-stage AIDS dementia complex. Grade 3 or higher nausea and/or vomiting.

- Sensitivity to pyrimethamine.

Gender: All

Minimum Age: 13 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Location
Facility:
Community Consortium of San Francisco | San Francisco, California, 94110, United States
Denver CPCRA / Denver Public Hlth | Denver, Colorado, 802044507, United States
Hill Health Corp | New Haven, Connecticut, 06519, United States
Wilmington Hosp / Med Ctr of Delaware | Wilmington, Delaware, 19899, United States
AIDS Research Consortium of Atlanta | Atlanta, Georgia, 30308, United States
AIDS Research Alliance - Chicago | Chicago, Illinois, 60657, United States
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med | New Orleans, Louisiana, 70112, United States
Comprehensive AIDS Alliance of Detroit | Detroit, Michigan, 48201, United States
Henry Ford Hosp | Detroit, Michigan, 48202, United States
North Jersey Community Research Initiative | Newark, New Jersey, 071032842, United States
Bronx Lebanon Hosp Ctr | Bronx, New York, 10456, United States
Addiction Research and Treatment Corp | Brooklyn, New York, 11201, United States
Clinical Directors Network of Region II | New York, New York, 10011, United States
Harlem AIDS Treatment Group / Harlem Hosp Ctr | New York, New York, 10037, United States
Portland Veterans Adm Med Ctr / Rsch & Education Grp | Portland, Oregon, 972109951, United States
Richmond AIDS Consortium | Richmond, Virginia, 23298, United States
Location Countries

United States

Verification Date

October 2012

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Source: ClinicalTrials.gov