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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00000966
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : August 26, 2008
Information provided by:

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:

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 Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Encephalitis
U.S. FDA Resources

Arms and Interventions

Outcome Measures

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   13 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

Concurrent Medication:


  • 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:


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00000966

United States, California
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
United States, Florida
Univ of Miami School of Medicine
Miami, Florida, United States, 331361013
United States, Massachusetts
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, United States, 01655
United States, New York
Bronx Municipal Hosp Ctr/Jacobi Med Ctr
Bronx, New York, United States, 10461
Montefiore Med Ctr / Bronx Municipal Hosp
Bronx, New York, United States, 10467
Bronx Veterans Administration / Mount Sinai Hosp
Bronx, New York, United States, 10468
Nassau County Med Ctr
East Meadow, New York, United States, 11554
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Cornell Univ Med Ctr
New York, New York, United States, 10021
SUNY - Stony Brook
Stony Brook, New York, United States, 117948153
United States, South Carolina
Julio Arroyo
West Columbia, South Carolina, United States, 29169
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Study Chair: Luft B
Study Chair: Remington J
More Information

ClinicalTrials.gov Identifier: NCT00000966     History of Changes
Other Study ID Numbers: ACTG 156
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: August 26, 2008
Last Verified: October 1994

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Evaluation
Drug Therapy, Combination
Administration, Oral
Acquired Immunodeficiency Syndrome

Additional relevant MeSH terms:
HIV Infections
Toxoplasmosis, Cerebral
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Protozoan Infections
Parasitic Diseases
Brain Abscess
Central Nervous System Protozoal Infections
Central Nervous System Parasitic Infections
Central Nervous System Infections
Protective Agents
Physiological Effects of Drugs