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

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ClinicalTrials.gov Identifier: NCT00000966

Recruitment Status : Completed

First Posted : August 31, 2001

Last Update Posted : August 26, 2008

Sponsor:

Collaborator:

National Institute of Allergy and Infectious Diseases (NIAID)

Information provided by:

National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information

First Submitted Date ^ICMJE

November 2, 1999

First Posted Date ^ICMJE

August 31, 2001

Last Update Posted Date

August 26, 2008

Study Start Date ^ICMJE

Not Provided

Primary Completion Date

Not Provided

Current Primary Outcome Measures ^ICMJE

Not Provided

Original Primary Outcome Measures ^ICMJE

Not Provided

Change History

Current Secondary Outcome Measures ^ICMJE

Not Provided

Original Secondary Outcome Measures ^ICMJE

Not Provided

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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.

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 Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1

Study Design ^ICMJE

Primary Purpose: Treatment

Condition ^ICMJE

Toxoplasmosis, Cerebral
HIV Infections

Intervention ^ICMJE

Drug: Azithromycin
Drug: Pyrimethamine
Drug: Leucovorin calcium

Study Arms ^ICMJE

Not Provided

Publications *

Saba J, Morlat P, Raffi F, Hazebroucq V, Joly V, Leport C, Vildé JL. Pyrimethamine plus azithromycin for treatment of acute toxoplasmic encephalitis in patients with AIDS. Eur J Clin Microbiol Infect Dis. 1993 Nov;12(11):853-6.
. Kamarulzaman A, Hoy J. Effect of folinic acid on haematological toxicity during treatment of cerebral toxoplasmosis in patients with AIDS. Annu Conf Australas Soc HIV Med. 1995 Nov 16-19;7:68 (abstract no 68)
Jacobson JM, Hafner R, Remington J, Farthing C, Holden-Wiltse J, Bosler EM, Harris C, Jayaweera DT, Roque C, Luft BJ; ACTG 156 Study Team. Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS. AIDS. 2001 Mar 30;15(5):583-9.

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Enrollment ^ICMJE

Original Enrollment ^ICMJE

Same as current

Study Completion Date ^ICMJE

Not Provided

Primary Completion Date

Not Provided

Eligibility Criteria ^ICMJE

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.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

13 Years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT00000966

Other Study ID Numbers ^ICMJE

ACTG 156

Has Data Monitoring Committee

Not Provided

U.S. FDA-regulated Product

Not Provided

IPD Sharing Statement ^ICMJE

Not Provided

Responsible Party

Not Provided

Study Sponsor ^ICMJE

Pfizer

Collaborators ^ICMJE

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators ^ICMJE

Study Chair:	Luft B
Study Chair:	Remington J

PRS Account

National Institute of Allergy and Infectious Diseases (NIAID)

Verification Date

October 1994

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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