Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

• ClinicalTrials.gov Identifier: NCT00000643
• Recruitment Status: Completed
• First Posted: August 31, 2001
• Last Update Posted: March 30, 2012
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease	Intervention/treatment	Phase
Toxoplasmosis, Cerebral; HIV Infections	Drug: Pyrimethamine; Drug: Leucovorin calcium	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Enrollment: 150 participants
• Masking: Double
• Primary Purpose: Prevention
• Official Title: Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients
• Actual Study Completion Date: May 1994

Arms and Interventions

Outcome Measures

Eligibility Criteria

• Ages Eligible for Study: 13 Years and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

  Show 24 Study Locations

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: BJ Luft
• Study Chair: JL Vilde

More Information

Publications:

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.

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.

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.

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.

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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00000643 History of Changes
• Other Study ID Numbers: ACTG 154; 11129 ( Registry Identifier: DAIDS ES Registry Number )
• First Posted: August 31, 2001
• Last Update Posted: March 30, 2012
• Last Verified: March 2012

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:

Toxoplasmosis, Cerebral; Toxoplasmosis; 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; Pyrimethamine; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Folic Acid Antagonists; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action