Chicago, Illinois 60657

  • HIV Infections

Purpose:

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).


Study summary:

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.


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.


Study is Available At:


Original ID:

CPCRA 001


NCT ID:

NCT00000666


Secondary ID:


Study Acronym:


Brief Title:

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


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


Overall Status:

Completed


Study Phase:

N/A


Genders:

Both


Minimum Age:

13 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Institute of Allergy and Infectious Disease (NIAID)


Oversight Authority:

United States: Federal Government


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Intervention Model: Parallel Assignment, Primary


Number of Arms:

0


Number of Groups:

0


Total Enrollment:

600


Enrollment Type:


Overall Contact Information

Official Name:Jacobson M
Study Chair

Study Dates

Completion Date:March 1992
Completion Type:Actual
Verification Date:October 2012
Last Changed Date:October 26, 2012
First Received Date:November 2, 1999

Study Outcomes

There are no available Study Outcomes

Study Interventions

Intervention Type:Drug
Name:Pyrimethamine

Study Arms

There are no available Study Arms

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Institute of Allergy and Infectious Disease (NIAID)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Reference
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.
PMID:1676364
Reference Type:Reference
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.
PMID:1346413
Reference Type:Reference
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.
PMID:8106772

Data Source: ClinicalTrials.gov

Date Processed: March 30, 2020

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