Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

HIV Infections Clinical Trial

Official title:

Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000643
• Other study ID #: ACTG 154
• Secondary ID: 11129
• Status: Completed
• Phase: Phase 2
• 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
• 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
• 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.

Related Conditions & MeSH terms

• HIV Infections
• Toxoplasmosis
• Toxoplasmosis, Cerebral

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