A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS

May 17, 2012 updated by: National Institute of Allergy and Infectious Diseases (NIAID)
To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.

Amended: Projected accrual increased to 50 patients. Original design: Patients receive study medications for a total of 6 weeks unless there are intervening events that require the discontinuation of study therapy. Patients are initially treated in the hospital (minimum of 7 days). Patients who are considered responders at day 7 may complete therapy on an outpatient basis. Nonresponders at day 7 may also be managed on an outpatient basis when it is medically appropriate.

Study Type

Interventional

Enrollment

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC CRS
      • Palo Alto, California, United States, 94304
        • Stanford CRS
      • San Diego, California, United States, 92103
        • Ucsd, Avrc Crs
    • Florida
      • Miami, Florida, United States, 33136
        • Univ. of Miami AIDS CRS
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Adult AIDS CRS
    • Missouri
      • St. Louis, Missouri, United States
        • Washington U CRS
    • New York
      • Buffalo, New York, United States, 14215
        • SUNY - Buffalo, Erie County Medical Ctr.
      • New York, New York, United States, 10016
        • NY Univ. HIV/AIDS CRS
      • New York, New York, United States, 10021
        • Cornell University A2201
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Ctr.
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Unc Aids Crs
      • Durham, North Carolina, United States, 27710
        • Duke Univ. Med. Ctr. Adult CRS
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Pitt CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

11 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Erythropoietin.
  • Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia (PCP).
  • Immunoglobulin therapy.
  • Alpha interferon.
  • Patients entering study on isoniazid (INH) may continue INH therapy.
  • Use of corticosteroids is discouraged. If corticosteroids are needed for the management of intracranial hypertension or cranial mass effect, use of dexamethasone is encouraged (4 g orally 4 times daily for 3 days and thereafter tapered over the next 10 to 14 days).

Patients are admitted into the study if they have:

  • Laboratory evidence of HIV infection or if they have an undetermined HIV infection status if they belong to a high-risk group for HIV infection.
  • Either a definite or presumptive diagnosis of toxoplasmic encephalitis. Patient or appropriate family member, or legal designee must be able to understand and sign a written informed consent.

Allowed:

  • HIV encephalopathy.

AMENDED:

  • Allows patients who have relapsed. Patients with a previous diagnosis of toxoplasmic encephalitis based on histopathology or documented neuroradiological response to pyrimethamine and sulfonamides or pyrimethamine and clindamycin and who have relapsed toxoplasmic encephalitis. Relapse must be documented by definite progression of lesions or appearance of new lesions compatible with toxoplasmic encephalitis.

Prior Medication:

Allowed if liver enzymes stable for 6 weeks prior to study entry:

  • Rifampin.
  • Isoniazid.

Exclusion Criteria

Co-existing Condition:

Patients with the following are excluded:

  • Infections of the central nervous system.
  • Malabsorption syndrome (3 or more loose stools a day for at least 4 weeks associated with an unintentional weight loss of at least 10 percent of body weight).
  • History of sensitivity to the study medication.
  • Malignancies requiring the use of cytotoxic chemotherapy.
  • Coma.
  • Diffuse central white matter lesions.
  • Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive).
  • Lymphoma of the central nervous system.
  • Cerebral Kaposi's sarcoma.
  • Hemorrhagic diathesis or active bleeding disorder.

Concurrent Medication:

Excluded:

  • Erythromycin or other macrolides.
  • Sulfonamides.
  • Immunomodulators.
  • Cytotoxic chemotherapy.
  • Amphotericin.
  • Dapsone.
  • Rifamycins.
  • Ganciclovir.
  • Allopurinol.
  • Antifolates.
  • Azidothymidine and other antiretrovirals and investigational agents not specifically allowed.
  • Folate supplements.
  • Isoniazid (INH) therapy may not be started while on therapy.

Concurrent Treatment:

Excluded:

  • Lymphocyte replacement.

Patients with the following are excluded:

  • Negative HIV antibodies by a federally licensed ELISA (as determined at or after study entry), unless there is documentation of a previously positive HIV culture or p24 antigen.
  • Coma.
  • Diffuse central white matter lesions.
  • Negative serology for Toxoplasma as performed at the Palo Alto Medical Foundation (unless biopsy is positive).
  • Lymphoma of the central nervous system.
  • Cerebral Kaposi's sarcoma.
  • Hemorrhagic diathesis or active bleeding disorder.
  • Unable to take oral medications reliably.
  • Any medical or social condition which, in the opinion of the investigator, would adversely affect either participation and/or compliance in this study.

Prior Medication:

Excluded:

  • Treatment for toxoplasmic encephalitis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Glaxo Wellcome
Upjohn

Investigators

  • Study Chair: Remington JS
  • Study Chair: Luft B

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

August 1, 1992

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

May 18, 2012

Last Update Submitted That Met QC Criteria

May 17, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 077P
  • 11052 (DAIDS ES Registry Number)
  • ACTG 077 PILOT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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