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

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00000666

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).

Condition	Intervention
Toxoplasmosis, Cerebral HIV Infections	Drug: Pyrimethamine

Study Type:	Interventional
Study Design:	Prevention, Parallel Assignment
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

Resource links provided by NLM:

MedlinePlus related topics: AIDS Encephalitis Toxoplasmosis

Drug Information available for: Pyrimethamine

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

600

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

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000666

Locations

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

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Jacobson M
Study Chair:	Besch CL

More Information

Publications:

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.

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.

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.

Study ID Numbers:	CPCRA 001
Study First Received:	November 2, 1999
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00000666 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Toxoplasmosis
AIDS-Related Opportunistic Infections
Pyrimethamine

Drug Evaluation
Encephalitis
Acquired Immunodeficiency Syndrome

Study placed in the following topic categories:

Pyrimethamine
Opportunistic Infections
Sexually Transmitted Diseases, Viral
Toxoplasmosis, Cerebral
Folate
Brain Diseases
Vitamin B9
Antimalarials
AIDS-Related Opportunistic Infections
Suppuration
Parasitic Diseases
Retroviridae Infections
Protozoan Infections

Acquired Immunodeficiency Syndrome
Central Nervous System Diseases
Folic Acid Antagonists
Folinic Acid
Immunologic Deficiency Syndromes
Toxoplasmosis
Encephalitis
Virus Diseases
Folic Acid
Central Nervous System Infections
HIV Infections
Abscess
Sexually Transmitted Diseases

Additional relevant MeSH terms:

Pyrimethamine
Anti-Infective Agents
Communicable Diseases
Antiprotozoal Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Toxoplasmosis, Cerebral
Central Nervous System Viral Diseases
Infection
Brain Diseases
Central Nervous System Parasitic Infections
Antimalarials
Antiparasitic Agents
Therapeutic Uses

Suppuration
Parasitic Diseases
Retroviridae Infections
Protozoan Infections
RNA Virus Infections
Immune System Diseases
Coccidiosis
Acquired Immunodeficiency Syndrome
Nervous System Diseases
Central Nervous System Diseases
Brain Abscess
Enzyme Inhibitors
Folic Acid Antagonists
Pharmacologic Actions
Toxoplasmosis

ClinicalTrials.gov processed this record on July 02, 2009