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Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

Primary Purpose

Toxoplasmosis, Cerebral, HIV Infections

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pyrimethamine
Leucovorin calcium
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, Pyrimethamine, Leucovorin, Drug Evaluation, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Brain Diseases

Eligibility Criteria

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

Inclusion Criteria Concurrent Medication: Allowed: Zidovudine (AZT), didanosine (ddI), dideoxycytidine (ddC), erythropoietin (Eprex), other agents granted Treatment IND or expanded access status. Investigational triazoles. Pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia (PCP). Patients with the following are excluded: History of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue. Focal neural abnormalities (except peripheral neuropathy) or mass lesions on a previous computerized tomography (CT) scan or magnetic resonance image (MRI), unless subsequent workup rules out toxoplasmosis, in which case abnormalities must have been stable for at least 2 months. Known or suspected allergy or severe intolerance to study drugs. Patients must have: Positive toxoplasma serology. HIV infection. Willingness and ability to comply with the protocol and capability of giving written informed consent. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Current diagnosis of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue. Known or suspected allergy or severe intolerance to study drugs. Concurrent Medication: Excluded: Anticoagulants. Other antifolates, sulfonamides, fansidar, macrolides, 5-fluorouracil, dapsone, or any other agent with known activity against Toxoplasma gondii.

Sites / Locations

  • Stanford CRS
  • Harbor-UCLA Med. Ctr. CRS
  • Univ. of Miami AIDS CRS
  • Northwestern University CRS
  • Rush Univ. Med. Ctr. ACTG CRS
  • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
  • Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
  • Johns Hopkins Adult AIDS CRS
  • Bmc Actg Crs
  • University of Minnesota, ACTU
  • St. Louis ConnectCare, Infectious Diseases Clinic
  • Washington U CRS
  • NJ Med. School CRS
  • SUNY - Buffalo, Erie County Medical Ctr.
  • Beth Israel Med. Ctr. (Mt. Sinai)
  • NY Univ. HIV/AIDS CRS
  • Cornell University A2201
  • Memorial Sloan-Kettering Cancer Ctr.
  • Univ. of Rochester ACTG CRS
  • Unc Aids Crs
  • Duke Univ. Med. Ctr. Adult CRS
  • Univ. of Cincinnati CRS
  • Case CRS
  • Pitt CRS

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
October 26, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000643
Brief Title
Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients
Official Title
Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
May 1994 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
To evaluate the effectiveness of pyrimethamine (given with leucovorin calcium versus placebo (an inactive substance) for the primary prophylaxis (prevention) of cerebral toxoplasmosis in HIV-infected patients. Cerebral toxoplasmosis is one of the most frequently encountered opportunistic infections in the course of AIDS. The mortality (death) rate is estimated to be greater than 50 percent. Pyrimethamine is a drug that appears promising for the primary prevention of cerebral toxoplasmosis in HIV-infected patients.
Detailed Description
Cerebral toxoplasmosis is one of the most frequently encountered opportunistic infections in the course of AIDS. The mortality (death) rate is estimated to be greater than 50 percent. Pyrimethamine is a drug that appears promising for the primary prevention of cerebral toxoplasmosis in HIV-infected patients. AMENDED: 04-04-91 On the first day of therapy, a loading dose is given. After the first day, patients take pyrimethamine or placebo 3 times a week. Patients also take leucovorin calcium orally three times weekly. Enrollment occurs over approximately 12 months. All patients are followed on study until a common study close-out date and final analysis of the study. It is anticipated that this common close-out will occur when the mean duration of time on study therapy will be 3 years (approximately in January, 1994). ORIGINAL design: On the first day of treatment, patients receive a loading dose of pyrimethamine or placebo, plus of leucovorin calcium. After the first day, patients take pyrimethamine or placebo three times a week. Patients also take folinic acid orally three times weekly. The mean duration of study participation is 3 years.

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, Pyrimethamine, Leucovorin, Drug Evaluation, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Brain Diseases

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Masking
Double
Enrollment
150 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Pyrimethamine
Intervention Type
Drug
Intervention Name(s)
Leucovorin calcium

10. Eligibility

Sex
All
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria Concurrent Medication: Allowed: Zidovudine (AZT), didanosine (ddI), dideoxycytidine (ddC), erythropoietin (Eprex), other agents granted Treatment IND or expanded access status. Investigational triazoles. Pentamidine for primary prophylaxis of Pneumocystis carinii pneumonia (PCP). Patients with the following are excluded: History of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue. Focal neural abnormalities (except peripheral neuropathy) or mass lesions on a previous computerized tomography (CT) scan or magnetic resonance image (MRI), unless subsequent workup rules out toxoplasmosis, in which case abnormalities must have been stable for at least 2 months. Known or suspected allergy or severe intolerance to study drugs. Patients must have: Positive toxoplasma serology. HIV infection. Willingness and ability to comply with the protocol and capability of giving written informed consent. Exclusion Criteria Co-existing Condition: Patients with the following conditions or symptoms are excluded: Current diagnosis of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue. Known or suspected allergy or severe intolerance to study drugs. Concurrent Medication: Excluded: Anticoagulants. Other antifolates, sulfonamides, fansidar, macrolides, 5-fluorouracil, dapsone, or any other agent with known activity against Toxoplasma gondii.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
BJ Luft
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
JL Vilde
Official's Role
Study Chair
Facility Information:
Facility Name
Stanford CRS
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Harbor-UCLA Med. Ctr. CRS
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
Univ. of Miami AIDS CRS
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Rush Univ. Med. Ctr. ACTG CRS
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
City
New Orleans
State/Province
Louisiana
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Bmc Actg Crs
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
University of Minnesota, ACTU
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
St. Louis ConnectCare, Infectious Diseases Clinic
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
Washington U CRS
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
NJ Med. School CRS
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
SUNY - Buffalo, Erie County Medical Ctr.
City
Buffalo
State/Province
New York
ZIP/Postal Code
14215
Country
United States
Facility Name
Beth Israel Med. Ctr. (Mt. Sinai)
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Cornell University A2201
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Ctr.
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Univ. of Rochester ACTG CRS
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Unc Aids Crs
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke Univ. Med. Ctr. Adult CRS
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Univ. of Cincinnati CRS
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Case CRS
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Pitt CRS
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9114191
Citation
Rousseau F, Pueyo S, Morlat P, Hafner R, Chene G, Leport C, Luft BJ, Miro J, Aubertin J, Salamon R, Vilde JL. Increased risk of toxoplasmic encephalitis in human immunodeficiency virus-infected patients with pyrimethamine-related rash. ANRS 005-ACTG 154 Trial Group. Agence Nationale de Recherche sur le SIDA (ANRS-INSERM) and the NIAID-AIDS Clinical Trials Group. Clin Infect Dis. 1997 Mar;24(3):396-402. doi: 10.1093/clinids/24.3.396.
Results Reference
background
Citation
Leport C, Chene G, Farinotti R, Ecobichon J-L, Petavin G, Sagardoy G, Morlat P, Hafner R, Luft B, Salamon R, Vilde J-L. Determination of pyrimethamine serum levels in a primary prophylaxis trial for toxoplasmic encephalitis. Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:159
Results Reference
background
PubMed Identifier
8537688
Citation
Leport C, Chene G, Morlat P, Luft BJ, Rousseau F, Pueyo S, Hafner R, Miro J, Aubertin J, Salamon R, Vilde JL. Pyrimethamine for primary prophylaxis of toxoplasmic encephalitis in patients with human immunodeficiency virus infection: a double-blind, randomized trial. ANRS 005-ACTG 154 Group Members. Agence Nationale de Recherche sur le SIDA. AIDS Clinical Trial Group. J Infect Dis. 1996 Jan;173(1):91-7. doi: 10.1093/infdis/173.1.91.
Results Reference
background
PubMed Identifier
9170421
Citation
Pueyo S, Salmi LR, Chene G, Leport C, Morlat P, Dequae L, Gregoire V, Hafner R, Vilde JL, Luft BJ, Aubertin J, Salamon R. Survival after AIDS-defining events in patients with < 200 lymphocytes CD4+ x 10(6)/L who are toxoplasmosis antibody positive. ANRS 005/ACTG 154 Trial Group. J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Apr 15;14(5):459-64. doi: 10.1097/00042560-199704150-00010.
Results Reference
background
PubMed Identifier
8931787
Citation
Derouin F, Leport C, Pueyo S, Morlat P, Letrillart B, Chene G, Ecobichon JL, Luft B, Aubertin J, Hafner R, Vilde JL, Salamon R. Predictive value of Toxoplasma gondii antibody titres on the occurrence of toxoplasmic encephalitis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group. AIDS. 1996 Nov;10(13):1521-7. doi: 10.1097/00002030-199611000-00010.
Results Reference
background
Citation
Chene G, Morlat P, Hafner R, Aboulker JP, Luft B, Dormont J, Vilde JL, Salamon R. Intent-to-treat versus on treatment analysis: how to interpret the results of a clinical trial? Experience from ANRS 005/ACTG 154 study. Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16:100
Results Reference
background
PubMed Identifier
9620807
Citation
Chene G, Morlat P, Leport C, Hafner R, Dequae L, Charreau I, Aboulker JP, Luft B, Aubertin J, Vilde JL, Salamon R. Intention-to-treat vs. on-treatment analyses of clinical trial data: experience from a study of pyrimethamine in the primary prophylaxis of toxoplasmosis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group. Control Clin Trials. 1998 Jun;19(3):233-48. doi: 10.1016/s0197-2456(97)00145-1.
Results Reference
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Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

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