Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000643

Collaborator

(none)

150

Enrollment

Locations

6.3

Patients Per Site

Study Details

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

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

Masking:

Double

Primary Purpose:

Prevention

Official Title:

Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients

Actual Study Completion Date :

May 1, 1994

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford CRS	Palo Alto	California	United States	94304
2	Harbor-UCLA Med. Ctr. CRS	Torrance	California	United States	90502
3	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
4	Northwestern University CRS	Chicago	Illinois	United States	60611
5	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60611
6	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
7	Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU	New Orleans	Louisiana	United States
8	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
9	Bmc Actg Crs	Boston	Massachusetts	United States	02118
10	University of Minnesota, ACTU	Minneapolis	Minnesota	United States	55455
11	St. Louis ConnectCare, Infectious Diseases Clinic	Saint Louis	Missouri	United States
12	Washington U CRS	Saint Louis	Missouri	United States
13	NJ Med. School CRS	Newark	New Jersey	United States	07103
14	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
15	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10003
16	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
17	Cornell University A2201	New York	New York	United States	10021
18	Memorial Sloan-Kettering Cancer Ctr.	New York	New York	United States	10021
19	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
20	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
21	Duke Univ. Med. Ctr. Adult CRS	Durham	North Carolina	United States	27710
22	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
23	Case CRS	Cleveland	Ohio	United States	44106
24	Pitt CRS	Pittsburgh	Pennsylvania	United States	15213