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

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00000794
• Date of registration: 02/11/1999
• Primary sponsor: National Institute of Allergy and Infectious Disease (NIAID)
• Public title: Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis
• Scientific title: Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis
• Date of first enrolment: August 1992
• Target sample size: 100
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00000794
• Study type: Interventional
• Study design: Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Countries of recruitment

France, United States

Contacts

• Name: Chirgwin K

• Name: Luft B

Key inclusion & exclusion criteria

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.



Age minimum: 13 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

HIV Infections

Toxoplasmosis, Cerebral

Intervention(s)

Drug: Atovaquone

Drug: Clarithromycin

Drug: Leucovorin calcium

Drug: Pyrimethamine

Drug: Sulfadiazine

Secondary ID(s)

11214

ACTG 237

ANRS 039

Source(s) of Monetary Support

Please refer to primary and secondary sponsors