Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000643
First received: November 2, 1999
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Toxoplasmosis, Cerebral
HIV Infections
Drug: Pyrimethamine
Drug: Leucovorin calcium
Phase 2

Study Type: Interventional
Study Design: Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

Resource links provided by NLM:


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

Estimated Enrollment: 150
Study Completion Date: May 1994
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000643

  Hide Study Locations
Locations
United States, California
Stanford CRS
Palo Alto, California, United States, 94304
Harbor-UCLA Med. Ctr. CRS
Torrance, California, United States, 90502
United States, Florida
Univ. of Miami AIDS CRS
Miami, Florida, United States, 33136
United States, Illinois
Northwestern University CRS
Chicago, Illinois, United States, 60611
Rush Univ. Med. Ctr. ACTG CRS
Chicago, Illinois, United States, 60611
United States, Indiana
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, United States, 46202
United States, Louisiana
Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
New Orleans, Louisiana, United States
United States, Maryland
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Bmc Actg Crs
Boston, Massachusetts, United States, 02118
United States, Minnesota
University of Minnesota, ACTU
Minneapolis, Minnesota, United States, 55455
United States, Missouri
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri, United States
Washington U CRS
St Louis, Missouri, United States
United States, New Jersey
NJ Med. School CRS
Newark, New Jersey, United States, 07103
United States, New York
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, United States, 14215
Memorial Sloan-Kettering Cancer Ctr.
New York, New York, United States, 10021
NY Univ. HIV/AIDS CRS
New York, New York, United States, 10016
Cornell University A2201
New York, New York, United States, 10021
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, United States, 10003
Univ. of Rochester ACTG CRS
Rochester, New York, United States, 14642
United States, North Carolina
Unc Aids Crs
Chapel Hill, North Carolina, United States, 27599
Duke Univ. Med. Ctr. Adult CRS
Durham, North Carolina, United States, 27710
United States, Ohio
Univ. of Cincinnati CRS
Cincinnati, Ohio, United States, 45267
Case CRS
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Pitt CRS
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
Investigators
Study Chair: BJ Luft
Study Chair: JL Vilde
  More Information

Publications:
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
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

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000643     History of Changes
Other Study ID Numbers: ACTG 154, 11129
Study First Received: November 2, 1999
Last Updated: March 29, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Toxoplasmosis
Pyrimethamine
Leucovorin
Drug Evaluation
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Brain Diseases

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Toxoplasmosis
Toxoplasmosis, Cerebral
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Coccidiosis
Protozoan Infections
Parasitic Diseases
Brain Abscess
Abscess
Suppuration
Infection
Central Nervous System Protozoal Infections
Central Nervous System Parasitic Infections
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Central Nervous System Infections
Leucovorin
Levoleucovorin
Pyrimethamine
Vitamin B Complex

ClinicalTrials.gov processed this record on July 22, 2014