A Study of Azithromycin Plus Pyrimethamine in the Treatment of a Brain Infection in Patients With AIDS

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT00000966

Collaborator

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

Enrollment

Locations

4.1

Patients Per Site

Study Details

Study Description

Brief Summary

To evaluate the effectiveness and toxicity of oral azithromycin and pyrimethamine as acute therapy for toxoplasmic encephalitis in AIDS patients. To assess the toxicity and effectiveness of azithromycin alone as maintenance therapy.

Encephalitis caused by Toxoplasma gondii is the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. Standard treatment for toxoplasmic encephalitis is associated with serious adverse effects. Thus, alternative treatments are needed.

Condition or Disease	Intervention/Treatment	Phase
Toxoplasmosis, Cerebral HIV Infections	Drug: Azithromycin Drug: Pyrimethamine Drug: Leucovorin calcium	Phase 1

Detailed Description

Patients with toxoplasmosis are given azithromycin at doses starting at the lowest dose for the first cohort, an intermediate dose for the second cohort, and a higher dose for the third cohort. Subsequent cohorts may receive azithromycin in increased dosage, if needed to determine the MTD. All patients also receive pyrimethamine. Folinic acid is also provided for as long as patients receive pyrimethamine. Patients are evaluated for clinical response to treatment at days 3, 7, and 14, and weekly for 6 weeks. Maintenance treatment with azithromycin continues for an additional 24 weeks. Patients who complete the study period without relapse or significant toxicity are offered continued therapy by the drug company and are followed for survival and relapse on a monthly basis for 1 year. After the MTD is determined, a subsequent cohort may be added for special studies.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Dose-Escalation, Phase I/II Study of Oral Azithromycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS

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:

Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).
Allowed during maintenance period (weeks 7 - 24):
Zidovudine and other antiretrovirals available through treatment IND mechanisms, ganciclovir, and maintenance doses of amphotericin (other investigational therapies require permission from the study chair), steroids for the treatment of acute PCP.
Isoniazid (INH) only for patients already on INH.

Patients must have the following:

HIV infection or belong to high-risk group. Presumptive or definite diagnosis of toxoplasmic encephalitis.
Each patient, or his/her appropriate family member, or legal designee must be able to understand and sign a written informed consent, in accordance with the local practices at each site.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

History of cerebral toxoplasmosis or toxoplasmosis infection in any other organ or tissue.
Coma.
More than 72 hours of treatment for current episode of toxoplasmic encephalitis prior to study entry.
Central nervous system (CNS) lymphoma.
Cerebral Kaposi's sarcoma.
Active hepatitis or clinical jaundice.
History of serious hypersensitivity or intolerance to any of the study drugs.
Serum or cerebrospinal fluid (CSF) positive for cryptococcus antigen or culture.
Malignancies requiring use of cytotoxic chemotherapy.
Inability to take oral therapy reliably.
Malabsorption syndrome.

Concurrent Medication:

Excluded:

Opportunistic infection requiring either acute treatment or maintenance therapy with azithromycin, erythromycin or other macrolides, sulfonamides, amphotericin, dapsone, ganciclovir, antifolates, and other investigational agents except erythropoietin. For first 6 weeks of treatment, patients may not receive treatment with erythromycin (or other macrolides), sulfonamides, immunomodulators with the exception of alpha interferon, lymphocyte replacement, cytotoxic chemotherapy, dapsone, ganciclovir, rifampicin, coumadin, antiretrovirals, and investigational agents other than erythropoietin.

Patients with the following are excluded:

Negative HIV antibodies by a federally licensed ELISA, unless there is documentation of a previously positive HIV culture or p24 antigen.
Infections of the central nervous system.
Malignancies requiring the use of cytotoxic chemotherapy.
Any medical or social condition that, in the opinion of the investigator, would adversely affect participation and/or compliance in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles County - USC Med Ctr	Los Angeles	California	United States	90033
2	Univ of Miami School of Medicine	Miami	Florida	United States	331361013
3	Univ of Massachusetts Med Ctr	Worcester	Massachusetts	United States	01655
4	Bronx Municipal Hosp Ctr/Jacobi Med Ctr	Bronx	New York	United States	10461
5	Montefiore Med Ctr / Bronx Municipal Hosp	Bronx	New York	United States	10467
6	Bronx Veterans Administration / Mount Sinai Hosp	Bronx	New York	United States	10468
7	Nassau County Med Ctr	East Meadow	New York	United States	11554
8	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
9	Cornell Univ Med Ctr	New York	New York	United States	10021
10	SUNY - Stony Brook	Stony Brook	New York	United States	117948153
11	Julio Arroyo	West Columbia	South Carolina	United States	29169