Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis
- Conditions
- HIV InfectionsToxoplasmosis, Cerebral
- Registration Number
- NCT00000794
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (16)
Northwestern University CRS
🇺🇸Chicago, Illinois, United States
Cook County Hosp. CORE Ctr.
🇺🇸Chicago, Illinois, United States
Johns Hopkins Adult AIDS CRS
🇺🇸Baltimore, Maryland, United States
Univ. of Hawaii at Manoa, Leahi Hosp.
🇺🇸Honolulu, Hawaii, United States
St. Louis ConnectCare, Infectious Diseases Clinic
🇺🇸Saint Louis, Missouri, United States
USC CRS
🇺🇸Los Angeles, California, United States
Queens Med. Ctr.
🇺🇸Honolulu, Hawaii, United States
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
🇺🇸Indianapolis, Indiana, United States
Methodist Hosp. of Indiana
🇺🇸Indianapolis, Indiana, United States
NY Univ. HIV/AIDS CRS
🇺🇸New York, New York, United States
Washington U CRS
🇺🇸Saint Louis, Missouri, United States
SUNY - Buffalo, Erie County Medical Ctr.
🇺🇸Buffalo, New York, United States
Beth Israel Med. Ctr. (Mt. Sinai)
🇺🇸New York, New York, United States
Univ. of Miami AIDS CRS
🇺🇸Miami, Florida, United States
The Ohio State Univ. AIDS CRS
🇺🇸Columbus, Ohio, United States
Univ. of Cincinnati CRS
🇺🇸Cincinnati, Ohio, United States