Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To evaluate the efficacy, safety, and tolerance of atovaquone with either pyrimethamine or sulfadiazine in AIDS patients with toxoplasmic encephalitis.

AIDS patients with toxoplasmic encephalitis who receive the standard therapy combination of sulfadiazine and pyrimethamine experience a high frequency of severe toxicity. Atovaquone, an antibiotic that has demonstrated efficacy against toxoplasmosis in animal models and in preclinical testing has been well tolerated, is now available as a suspension, which is more readily absorbed than the tablet form of the drug. The efficacy and safety of atovaquone in combination with sulfadiazine or pyrimethamine will be studied.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

AIDS patients with toxoplasmic encephalitis who receive the standard therapy combination of sulfadiazine and pyrimethamine experience a high frequency of severe toxicity. Atovaquone, an antibiotic that has demonstrated efficacy against toxoplasmosis in animal models and in preclinical testing has been well tolerated, is now available as a suspension, which is more readily absorbed than the tablet form of the drug. The efficacy and safety of atovaquone in combination with sulfadiazine or pyrimethamine will be studied.

Seventy patients are randomized to receive atovaquone with either pyrimethamine or sulfonamides for up to 48 weeks. Additionally, three cohorts of 10 patients each who have a history of treatment-limiting toxicity to pyrimethamine, sulfadiazine, or both drugs receive atovaquone plus the alternate drug or atovaquone plus clarithromycin. All patients receiving pyrimethamine also receive leucovorin protection.

PER AMENDMENT 4/3/96:

The open treatment groups are: Atovaquone plus pyrimethamine for patients with acute toxoplasmic encephalitis who have no treatment limiting toxicity to pyrimethamine, and Atovaquone plus clarithromycin for patients with acute toxoplasmic encephalitis who have treatment limiting toxicity to both pyrimethamine and sulfadiazine. The following arms closed on 12/22/95: Randomization to the atovaquone plus sulfadiazine arm for patients with acute toxoplasmic encephalitis who had no treatment limiting toxicity to pyrimethamine or sulfonamides, and Atovaquone plus sulfadiazine for patients with acute toxoplasmic encephalitis who had treatment limiting toxicity to pyrimethamine. The following arm closed on 9/26/95: Atovaquone plus pyrimethamine for patients with acute toxoplasmic encephalitis who had treatment limiting toxicity to sulfonamides. NOTE: Any patients enrolled in previous versions will continue to be treated with that same drug treatment and followed under their previous version guidelines.

Study Type

Interventional

Enrollment

100

Phase

  • Phase 2

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, 900331079
        • USC CRS
    • Florida
      • Miami, Florida, United States, 331361013
        • Univ. of Miami AIDS CRS
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ. of Hawaii at Manoa, Leahi Hosp.
      • Honolulu, Hawaii, United States, 96816
        • Queens Med. Ctr.
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp. CORE Ctr.
      • Chicago, Illinois, United States, 60611
        • Northwestern University CRS
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Methodist Hosp. of Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Adult AIDS CRS
    • Missouri
      • Saint Louis, Missouri, United States
        • St. Louis ConnectCare, Infectious Diseases Clinic
      • Saint Louis, Missouri, United States, 63110
        • Washington U CRS
    • New York
      • Buffalo, New York, United States, 13210
        • SUNY - Buffalo, Erie County Medical Ctr.
      • New York, New York, United States, 10003
        • Beth Israel Med. Ctr. (Mt. Sinai)
      • New York, New York, United States
        • NY Univ. HIV/AIDS CRS
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Univ. of Cincinnati CRS
      • Columbus, Ohio, United States, 432101228
        • The Ohio State Univ. AIDS 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:

  • Aerosolized pentamidine for PCP prophylaxis.

PER AMENDMENT 4/3/96:

  • History of treatment limiting toxicity to pyrimethamine. Patients with a history of treatment limiting toxicity to both pyrimethamine and sulfonamides will be assigned to receive atovaquone plus clarithromycin.

Patients must have:

  • Documented HIV infection or diagnosis of AIDS (except for CD4 count < 200 cells/mm3).
  • Toxoplasmic encephalitis.
  • Ability to give informed consent or legal designee who could give consent.

PER AMENDMENT 4/3/96:

  • NOTE - A history of treatment limiting toxicity to both pyrimethamine and sulfonamides will result in the patient being enrolled in the atovaquone plus clarithromycin arm.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Coma.
  • Opportunistic infection that requires either acute or maintenance treatment with disallowed medications.
  • Any infections or neoplasms of the central nervous system other than Toxoplasma, HIV encephalopathy, or syphilis.
  • Unable to take oral study drugs.
  • Malabsorption (i.e., three or more episodes of diarrhea per day that has caused >= 10 percent loss of body weight over the past 4 weeks).
  • Positive CSF or serum for Cryptococcus antigen or culture (a positive serum antigen only is acceptable, provided patient received prior antifungal therapy and is on maintenance, and the likelihood of recurrence is low).
  • Malignancy requiring use of cytotoxic chemotherapy.
  • Medical or social condition that would adversely affect study participation or compliance.

Concurrent Medication:

Excluded:

  • Trimethoprim-sulfamethoxazole.
  • Primaquine.
  • Sulfonamides.
  • Antifolates.
  • Dapsone.
  • Clarithromycin (except for patients in the cohort to receive this drug).
  • Azithromycin.
  • Clindamycin.
  • Other macrolides.
  • Gamma interferon.
  • Metoclopramide.
  • G-CSF or GM-CSF.

Excluded in patients receiving clarithromycin as study drug:

  • Terfenadine, astemizole, or any other long-acting, non-sedating antihistamines.

PER AMENDMENT 4/3/96:

  • Cisapride - may increase GI motility and may increase drug absorption.

Patients with the following prior conditions are excluded:

  • History of treatment-limiting toxicity to atovaquone.
  • Receipt of > 96 hours (per amendment) of treatment prior to study entry for the current episode of 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
  • Interventional Model: Parallel Assignment

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)

Investigators

  • 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)

April 1, 1998

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 (Actual)

October 28, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 237
  • ANRS 039
  • 11214 (DAIDS-ES)

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.

Clinical Trials on HIV Infections

Clinical Trials on Clarithromycin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malawi

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe