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

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	Complete list of historical versions of study NCT00000966 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	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	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. 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	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	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; (submitted: June 23, 2005)	45
Original Enrollment ICMJE	Same as current
Study Completion Date	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	Sexes Eligible for Study: All
Ages	13 Years and older (Child, Adult, Senior)
Accepts Healthy Volunteers	No
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	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