Clinical trial NCT00000666: A Randomized Prospective Study of Pyrimethamine Therapy for Prevention of Toxoplasmic Encephalitis in HIV-Infected Individuals With Serologic Evidence of Latent Toxoplasma Gondii Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Toxoplasmosis, Cerebral
HIV Infections
Keywords: Toxoplasmosis
AIDS-Related Opportunistic Infections
Pyrimethamine
Drug Evaluation
Encephalitis
Acquired Immunodeficiency Syndrome
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 600
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Community Consortium of San Francisco
state: California
city: Denver
country: United States
facility: Denver CPCRA / Denver Public Hlth
state: Colorado
city: New Haven
country: United States
facility: Hill Health Corp
state: Connecticut
city: Wilmington
country: United States
facility: Wilmington Hosp / Med Ctr of Delaware
state: Delaware
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Chicago
country: United States
facility: AIDS Research Alliance - Chicago
state: Illinois
city: New Orleans
country: United States
facility: Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
state: Louisiana
city: Detroit
country: United States
facility: Comprehensive AIDS Alliance of Detroit
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hosp
state: Michigan
city: Newark
country: United States
facility: North Jersey Community Research Initiative
state: New Jersey
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: Brooklyn
country: United States
facility: Addiction Research and Treatment Corp
state: New York
city: New York
country: United States
facility: Clinical Directors Network of Region II
state: New York
city: New York
country: United States
facility: Harlem AIDS Treatment Group / Harlem Hosp Ctr
state: New York
city: Portland
country: United States
facility: Portland Veterans Adm Med Ctr / Rsch & Education Grp
state: Oregon
city: Richmond
country: United States
facility: Richmond AIDS Consortium
state: Virginia
Study officials:
name: Jacobson M
role: STUDY_CHAIR
name: Besch CL
role: STUDY_CHAIR
References:
citation: Jacobson MA, Besch CL, Child C, Hafner R, Muth K, Deyton L. Clinical programs for clinical research on AIDS: description of a randomized prospective study of clindamycin versus pyrimethamine for prevention of Toxoplasma gondii infection. Eur J Clin Microbiol Infect Dis. 1991 Mar;10(3):195-8. doi: 10.1007/BF01964462.
citation: Jacobson MA, Besch CL, Child C, Hafner R, Matts JP, Muth K, Wentworth DN, Deyton L. Toxicity of clindamycin as prophylaxis for AIDS-associated toxoplasmic encephalitis. Community Programs for Clinical Research on AIDS. Lancet. 1992 Feb 8;339(8789):333-4. doi: 10.1016/0140-6736(92)91649-s.
citation: Jacobson MA, Besch CL, Child C, Hafner R, Matts JP, Muth K, Wentworth DN, Neaton JD, Abrams D, Rimland D, et al. Primary prophylaxis with pyrimethamine for toxoplasmic encephalitis in patients with advanced human immunodeficiency virus disease: results of a randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS. J Infect Dis. 1994 Feb;169(2):384-94. doi: 10.1093/infdis/169.2.384.