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

Primary Purpose

Toxoplasmosis, Cerebral, HIV Infections

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Pyrimethamine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Toxoplasmosis, Cerebral focused on measuring Toxoplasmosis, AIDS-Related Opportunistic Infections, Pyrimethamine, Drug Evaluation, Encephalitis, Acquired Immunodeficiency Syndrome

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Community Consortium of San Francisco
  • Denver CPCRA / Denver Public Hlth
  • Hill Health Corp
  • Wilmington Hosp / Med Ctr of Delaware
  • AIDS Research Consortium of Atlanta
  • AIDS Research Alliance - Chicago
  • Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
  • Comprehensive AIDS Alliance of Detroit
  • Henry Ford Hosp
  • North Jersey Community Research Initiative
  • Bronx Lebanon Hosp Ctr
  • Addiction Research and Treatment Corp
  • Clinical Directors Network of Region II
  • Harlem AIDS Treatment Group / Harlem Hosp Ctr
  • Portland Veterans Adm Med Ctr / Rsch & Education Grp
  • Richmond AIDS Consortium

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2012
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000666
Brief 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
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

2. Study Status

Record Verification Date
October 2012
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 1992 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Toxoplasmosis, Cerebral, HIV Infections
Keywords
Toxoplasmosis, AIDS-Related Opportunistic Infections, Pyrimethamine, Drug Evaluation, Encephalitis, Acquired Immunodeficiency Syndrome

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Enrollment
600 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Pyrimethamine

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacobson M
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Besch CL
Official's Role
Study Chair
Facility Information:
Facility Name
Community Consortium of San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Denver CPCRA / Denver Public Hlth
City
Denver
State/Province
Colorado
ZIP/Postal Code
802044507
Country
United States
Facility Name
Hill Health Corp
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
Wilmington Hosp / Med Ctr of Delaware
City
Wilmington
State/Province
Delaware
ZIP/Postal Code
19899
Country
United States
Facility Name
AIDS Research Consortium of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
AIDS Research Alliance - Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60657
Country
United States
Facility Name
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Comprehensive AIDS Alliance of Detroit
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Henry Ford Hosp
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
North Jersey Community Research Initiative
City
Newark
State/Province
New Jersey
ZIP/Postal Code
071032842
Country
United States
Facility Name
Bronx Lebanon Hosp Ctr
City
Bronx
State/Province
New York
ZIP/Postal Code
10456
Country
United States
Facility Name
Addiction Research and Treatment Corp
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11201
Country
United States
Facility Name
Clinical Directors Network of Region II
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
Harlem AIDS Treatment Group / Harlem Hosp Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10037
Country
United States
Facility Name
Portland Veterans Adm Med Ctr / Rsch & Education Grp
City
Portland
State/Province
Oregon
ZIP/Postal Code
972109951
Country
United States
Facility Name
Richmond AIDS Consortium
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
1676364
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.
Results Reference
background
PubMed Identifier
1346413
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.
Results Reference
background
PubMed Identifier
8106772
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.
Results Reference
background

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

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