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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000666

Collaborator

(none)

600

Enrollment

Locations

37.5

Patients Per Site

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Toxoplasmosis, Cerebral HIV Infections	Drug: Pyrimethamine	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Intervention Model:

Parallel Assignment

Primary Purpose:

Prevention

Official Title:

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

Actual Study Completion Date :

Mar 1, 1992

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Community Consortium of San Francisco	San Francisco	California	United States	94110
2	Denver CPCRA / Denver Public Hlth	Denver	Colorado	United States	802044507
3	Hill Health Corp	New Haven	Connecticut	United States	06519
4	Wilmington Hosp / Med Ctr of Delaware	Wilmington	Delaware	United States	19899
5	AIDS Research Consortium of Atlanta	Atlanta	Georgia	United States	30308
6	AIDS Research Alliance - Chicago	Chicago	Illinois	United States	60657
7	Louisiana Comm AIDS Rsch Prog / Tulane Univ Med	New Orleans	Louisiana	United States	70112
8	Comprehensive AIDS Alliance of Detroit	Detroit	Michigan	United States	48201
9	Henry Ford Hosp	Detroit	Michigan	United States	48202
10	North Jersey Community Research Initiative	Newark	New Jersey	United States	071032842
11	Bronx Lebanon Hosp Ctr	Bronx	New York	United States	10456
12	Addiction Research and Treatment Corp	Brooklyn	New York	United States	11201
13	Clinical Directors Network of Region II	New York	New York	United States	10011
14	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York	United States	10037
15	Portland Veterans Adm Med Ctr / Rsch & Education Grp	Portland	Oregon	United States	972109951
16	Richmond AIDS Consortium	Richmond	Virginia	United States	23298