Toxoplasmosis, CerebralPhase 2NCT00000794
Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis
A Phase 2 study testing Sulfadiazine, Clarithromycin and Atovaquone in people with Toxoplasmosis, Cerebral and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 16 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 13 years and older
- Conditions the study is for
- Toxoplasmosis, Cerebral, HIV Infections
- What is being tested?
- Sulfadiazine, Clarithromycin and Atovaquone
- How many people
- 100 participants
- Where
- 16 sitesUnited States
- Study dates
- Start not givento Apr 1998
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
Johns Hopkins Adult AIDS CRS
Baltimore, Maryland, 21287
SUNY - Buffalo, Erie County Medical Ctr.
Buffalo, New York, 13210
Northwestern University CRS
Chicago, Illinois, 60611
Cook County Hosp. CORE Ctr.
Chicago, Illinois, 60612
Univ. of Cincinnati CRS
Cincinnati, Ohio, 452670405
The Ohio State Univ. AIDS CRS
Columbus, Ohio, 432101228
Queens Med. Ctr.
Honolulu, Hawaii, 96816
Univ. of Hawaii at Manoa, Leahi Hosp.
Honolulu, Hawaii, 96816
Indiana Univ. School of Medicine, Infectious Disease Research Clinic
Indianapolis, Indiana, 462025250
Methodist Hosp. of Indiana
Indianapolis, Indiana, 46202
USC CRS
Los Angeles, California, 900331079
Univ. of Miami AIDS CRS
Miami, Florida, 331361013
Beth Israel Med. Ctr. (Mt. Sinai)
New York, New York, 10003
NY Univ. HIV/AIDS CRS
New York, New York
Washington U CRS
St Louis, Missouri, 63110
St. Louis ConnectCare, Infectious Diseases Clinic
St Louis, Missouri
About this study
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.
Read the 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.
- Conditions
- Toxoplasmosis, Cerebral, HIV Infections
- Being tested
- Sulfadiazine, Clarithromycin, Atovaquone, Pyrimethamine, Leucovorin calcium
- Keywords
- Pyrimethamine, Leucovorin, Drug Therapy, Combination, Encephalitis, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, Clarithromycin, atovaquone, Toxoplasmosis, Cerebral, Sulfadiazine
- Medical subject headings
- Toxoplasmosis, Cerebral, HIV Infections, Encephalitis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SulfadiazineDrug
ClarithromycinDrug
AtovaquoneDrug
PyrimethamineDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study completionApr 1998
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Toxoplasmosis, CerebralStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
- Enrolment
- 100 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Luft B, Study chairChirgwin K, Study chair
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00000794
- Sponsor's protocol ID
- ACTG 237
- Other IDs
- ANRS 039, 11214
- Status last verified
- Oct 2021
- First submitted
- 2 Nov 1999
- Last updated
- 28 Oct 2021
- Results posted
- No
Publications
Chirgwin K, Hafner R, Leport C, Remington J, Andersen J, Bosler EM, Roque C, Rajicic N, McAuliffe V, Morlat P, Jayaweera DT, Vilde JL, Luft BJ. Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039. Clin Infect Dis. 2002 May 1;34(9):1243-50. doi: 10.1086/339551.
PubMed 11941551
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis
- ClinicalTrials.gov ID
- NCT00000794
- Acronym / sponsor ID
- ACTG 237
- Conditions
- Toxoplasmosis, Cerebral, HIV Infections
- Keywords
- Pyrimethamine, Leucovorin, Drug Therapy, Combination, Encephalitis, Acquired Immunodeficiency Syndrome, Antiprotozoal Agents, Clarithromycin, atovaquone
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study completion
- Apr 1998 (actual)
- First posted
- 31 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Intervention model
- Parallel groups
Who may qualify
- Ages
- 13 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (11 listed)
- Aerosolized pentamidine for PCP prophylaxis.
- 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.
- 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.
Key exclusion criteria (31 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sulfadiazine | Drug | – |
| Clarithromycin | Drug | – |
| Atovaquone | Drug | – |
| Pyrimethamine | Drug | – |
| Leucovorin calcium | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2021.
- Background: PubMed 11941551Chirgwin K, Hafner R, Leport C, Remington J, Andersen J, Bosler EM, Roque C, Rajicic N, McAuliffe V, Morlat P, Jayaweera DT, Vilde JL, Luft BJ. Randomized phase II trial of atovaquone with pyrimethamine or sulfadiazine for treatment of toxoplasmic encephalitis in patients with acquired immunodeficiency syndrome: ACTG 237/ANRS 039 Study. AIDS Clinical Trials Group 237/Agence Nationale de Recherche sur le SIDA, Essai 039. Clin Infect Dis. 2002 May 1;34(9):1243-50. doi: 10.1086/339551.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luft B study chair
Chirgwin K study chair
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sulfadiazine, Clarithromycin and Atovaquone in people with Toxoplasmosis, Cerebral and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00000794, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2021.