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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000666
• Other study ID #: CPCRA 001
• Status: Completed
• Phase: N/A
• First received: November 2, 1999
• Last updated: October 26, 2012
• Est. completion date: March 1992

Study information

• Verified date: October 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: March 1992
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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.

Study Design

Intervention Model: Parallel Assignment, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Communicable Diseases
• Encephalitis
• HIV Infections
• Infection
• Toxoplasmosis
• Toxoplasmosis, Cerebral

Intervention

Drug:
• Pyrimethamine

Locations

Country	Name	City	State
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Addiction Research and Treatment Corp	Brooklyn	New York
United States	AIDS Research Alliance - Chicago	Chicago	Illinois
United States	Denver CPCRA / Denver Public Hlth	Denver	Colorado
United States	Comprehensive AIDS Alliance of Detroit	Detroit	Michigan
United States	Henry Ford Hosp	Detroit	Michigan
United States	Hill Health Corp	New Haven	Connecticut
United States	Louisiana Comm AIDS Rsch Prog / Tulane Univ Med	New Orleans	Louisiana
United States	Clinical Directors Network of Region II	New York	New York
United States	Harlem AIDS Treatment Group / Harlem Hosp Ctr	New York	New York
United States	North Jersey Community Research Initiative	Newark	New Jersey
United States	Portland Veterans Adm Med Ctr / Rsch & Education Grp	Portland	Oregon
United States	Richmond AIDS Consortium	Richmond	Virginia
United States	Community Consortium of San Francisco	San Francisco	California
United States	Wilmington Hosp / Med Ctr of Delaware	Wilmington	Delaware

Sponsors (1)

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

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation