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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00000643
Other study ID # ACTG 154
Secondary ID 11129
Status Completed
Phase Phase 2
First received
Last updated
Est. completion date May 1994

Study information

Verified date October 2021
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 150
Est. completion date May 1994
Est. primary completion date
Accepts healthy volunteers No
Gender All
Age group 13 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Pyrimethamine

Leucovorin calcium


Locations

Country Name City State
United States Johns Hopkins Adult AIDS CRS Baltimore Maryland
United States Bmc Actg Crs Boston Massachusetts
United States SUNY - Buffalo, Erie County Medical Ctr. Buffalo New York
United States Unc Aids Crs Chapel Hill North Carolina
United States Northwestern University CRS Chicago Illinois
United States Rush Univ. Med. Ctr. ACTG CRS Chicago Illinois
United States Univ. of Cincinnati CRS Cincinnati Ohio
United States Case CRS Cleveland Ohio
United States Duke Univ. Med. Ctr. Adult CRS Durham North Carolina
United States Indiana Univ. School of Medicine, Infectious Disease Research Clinic Indianapolis Indiana
United States Univ. of Miami AIDS CRS Miami Florida
United States University of Minnesota, ACTU Minneapolis Minnesota
United States Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU New Orleans Louisiana
United States Beth Israel Med. Ctr. (Mt. Sinai) New York New York
United States Cornell University A2201 New York New York
United States Memorial Sloan-Kettering Cancer Ctr. New York New York
United States NY Univ. HIV/AIDS CRS New York New York
United States NJ Med. School CRS Newark New Jersey
United States Stanford CRS Palo Alto California
United States Pitt CRS Pittsburgh Pennsylvania
United States Univ. of Rochester ACTG CRS Rochester New York
United States St. Louis ConnectCare, Infectious Diseases Clinic Saint Louis Missouri
United States Washington U CRS Saint Louis Missouri
United States Harbor-UCLA Med. Ctr. CRS Torrance California

Sponsors (1)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (7)

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

Chêne G, Morlat P, Leport C, Hafner R, Dequae L, Charreau I, Aboulker JP, Luft B, Aubertin J, Vildé 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. — View Citation

Derouin F, Leport C, Pueyo S, Morlat P, Letrillart B, Chêne G, Ecobichon JL, Luft B, Aubertin J, Hafner R, Vildé 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. — View 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

Leport C, Chêne G, Morlat P, Luft BJ, Rousseau F, Pueyo S, Hafner R, Miro J, Aubertin J, Salamon R, Vildé 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. — View Citation

Pueyo S, Salmi LR, Chêne G, Leport C, Morlat P, Dequae L, Grégoire V, Hafner R, Vildé 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. — View Citation

Rousseau F, Pueyo S, Morlat P, Hafner R, Chène G, Leport C, Luft BJ, Miro J, Aubertin J, Salamon R, Vildé 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. — View Citation

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