Ignite Creation Date:
2025-12-25 @ 2:00 AM
Ignite Modification Date:
2025-12-26 @ 6:18 PM
Study NCT ID:
NCT00000794
Status:
COMPLETED
Last Update Posted:
2021-10-28
First Post:
1999-11-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['France']}, 'conditionBrowseModule': {'meshes': [{'id': 'D016781', 'term': 'Toxoplasmosis, Cerebral'}, {'id': 'D015658', 'term': 'HIV Infections'}, {'id': 'D004660', 'term': 'Encephalitis'}, {'id': 'D000163', 'term': 'Acquired Immunodeficiency Syndrome'}], 'ancestors': [{'id': 'D001922', 'term': 'Brain Abscess'}, {'id': 'D002494', 'term': 'Central Nervous System Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D020808', 'term': 'Central Nervous System Protozoal Infections'}, {'id': 'D020807', 'term': 'Central Nervous System Parasitic Infections'}, {'id': 'D010272', 'term': 'Parasitic Diseases'}, {'id': 'D014123', 'term': 'Toxoplasmosis'}, {'id': 'D003048', 'term': 'Coccidiosis'}, {'id': 'D011528', 'term': 'Protozoan Infections'}, {'id': 'D000038', 'term': 'Abscess'}, {'id': 'D013492', 'term': 'Suppuration'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D000086982', 'term': 'Blood-Borne Infections'}, {'id': 'D003141', 'term': 'Communicable Diseases'}, {'id': 'D015229', 'term': 'Sexually Transmitted Diseases, Viral'}, {'id': 'D012749', 'term': 'Sexually Transmitted Diseases'}, {'id': 'D016180', 'term': 'Lentivirus Infections'}, {'id': 'D012192', 'term': 'Retroviridae Infections'}, {'id': 'D012327', 'term': 'RNA Virus Infections'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D000091662', 'term': 'Genital Diseases'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D007153', 'term': 'Immunologic Deficiency Syndromes'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D000090862', 'term': 'Neuroinflammatory Diseases'}, {'id': 'D012897', 'term': 'Slow Virus Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D013411', 'term': 'Sulfadiazine'}, {'id': 'D017291', 'term': 'Clarithromycin'}, {'id': 'D053626', 'term': 'Atovaquone'}, {'id': 'D011739', 'term': 'Pyrimethamine'}, {'id': 'D002955', 'term': 'Leucovorin'}], 'ancestors': [{'id': 'D000096926', 'term': 'Benzenesulfonamides'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D013424', 'term': 'Sulfanilamides'}, {'id': 'D000814', 'term': 'Aniline Compounds'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D004917', 'term': 'Erythromycin'}, {'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D061065', 'term': 'Polyketides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009285', 'term': 'Naphthoquinones'}, {'id': 'D011809', 'term': 'Quinones'}, {'id': 'D009281', 'term': 'Naphthalenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D005575', 'term': 'Formyltetrahydrofolates'}, {'id': 'D013763', 'term': 'Tetrahydrofolates'}, {'id': 'D005492', 'term': 'Folic Acid'}, {'id': 'D011622', 'term': 'Pterins'}, {'id': 'D011621', 'term': 'Pteridines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D003067', 'term': 'Coenzymes'}, {'id': 'D045762', 'term': 'Enzymes and Coenzymes'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'count': 100}}, 'statusModule': {'overallStatus': 'COMPLETED', 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-10', 'completionDateStruct': {'date': '1998-04', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-10-27', 'studyFirstSubmitDate': '1999-11-02', 'studyFirstSubmitQcDate': '2001-08-30', 'lastUpdatePostDateStruct': {'date': '2021-10-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2001-08-31', 'type': 'ESTIMATED'}}, 'conditionsModule': {'keywords': ['Pyrimethamine', 'Leucovorin', 'Drug Therapy, Combination', 'Encephalitis', 'Acquired Immunodeficiency Syndrome', 'Antiprotozoal Agents', 'Clarithromycin', 'atovaquone', 'Toxoplasmosis, Cerebral', 'Sulfadiazine'], 'conditions': ['Toxoplasmosis, Cerebral', 'HIV Infections']}, 'referencesModule': {'references': [{'pmid': '11941551', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': 'To evaluate the efficacy, safety, and tolerance of atovaquone with either pyrimethamine or sulfadiazine in AIDS patients with toxoplasmic encephalitis.\n\nAIDS 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.', 'detailedDescription': '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.\n\nSeventy 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.\n\nPER AMENDMENT 4/3/96:\n\nThe 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '13 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria\n\nConcurrent Medication:\n\nAllowed:\n\n* Aerosolized pentamidine for PCP prophylaxis.\n\nPER AMENDMENT 4/3/96:\n\n* 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.\n\nPatients must have:\n\n* Documented HIV infection or diagnosis of AIDS (except for CD4 count \\< 200 cells/mm3).\n* Toxoplasmic encephalitis.\n* Ability to give informed consent or legal designee who could give consent.\n\nPER AMENDMENT 4/3/96:\n\n* 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.\n\nExclusion Criteria\n\nCo-existing Condition:\n\nPatients with the following symptoms or conditions are excluded:\n\n* Coma.\n* Opportunistic infection that requires either acute or maintenance treatment with disallowed medications.\n* Any infections or neoplasms of the central nervous system other than Toxoplasma, HIV encephalopathy, or syphilis.\n* Unable to take oral study drugs.\n* 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).\n* 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).\n* Malignancy requiring use of cytotoxic chemotherapy.\n* Medical or social condition that would adversely affect study participation or compliance.\n\nConcurrent Medication:\n\nExcluded:\n\n* Trimethoprim-sulfamethoxazole.\n* Primaquine.\n* Sulfonamides.\n* Antifolates.\n* Dapsone.\n* Clarithromycin (except for patients in the cohort to receive this drug).\n* Azithromycin.\n* Clindamycin.\n* Other macrolides.\n* Gamma interferon.\n* Metoclopramide.\n* G-CSF or GM-CSF.\n\nExcluded in patients receiving clarithromycin as study drug:\n\n* Terfenadine, astemizole, or any other long-acting, non-sedating antihistamines.\n\nPER AMENDMENT 4/3/96:\n\n* Cisapride - may increase GI motility and may increase drug absorption.\n\nPatients with the following prior conditions are excluded:\n\n* History of treatment-limiting toxicity to atovaquone.\n* Receipt of \\> 96 hours (per amendment) of treatment prior to study entry for the current episode of toxoplasmic encephalitis.'}, 'identificationModule': {'nctId': 'NCT00000794', 'briefTitle': 'Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis', 'organization': {'class': 'NIH', 'fullName': 'National Institute of Allergy and Infectious Diseases (NIAID)'}, 'officialTitle': 'Phase II Randomized Open-Label Trial of Atovaquone Plus Pyrimethamine and Atovaquone Plus Sulfadiazine for the Treatment of Acute Toxoplasmic Encephalitis', 'orgStudyIdInfo': {'id': 'ACTG 237'}, 'secondaryIdInfos': [{'id': 'ANRS 039'}, {'id': '11214', 'type': 'REGISTRY', 'domain': 'DAIDS-ES'}]}, 'armsInterventionsModule': {'interventions': [{'name': 'Sulfadiazine', 'type': 'DRUG'}, {'name': 'Clarithromycin', 'type': 'DRUG'}, {'name': 'Atovaquone', 'type': 'DRUG'}, {'name': 'Pyrimethamine', 'type': 'DRUG'}, {'name': 'Leucovorin calcium', 'type': 'DRUG'}]}, 'contactsLocationsModule': {'locations': [{'zip': '900331079', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'USC CRS', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '331361013', 'city': 'Miami', 'state': 'Florida', 'country': 'United States', 'facility': 'Univ. of Miami AIDS CRS', 'geoPoint': {'lat': 25.77427, 'lon': -80.19366}}, {'zip': '96816', 'city': 'Honolulu', 'state': 'Hawaii', 'country': 'United States', 'facility': 'Queens Med. Ctr.', 'geoPoint': {'lat': 21.30694, 'lon': -157.85833}}, {'zip': '96816', 'city': 'Honolulu', 'state': 'Hawaii', 'country': 'United States', 'facility': 'Univ. of Hawaii at Manoa, Leahi Hosp.', 'geoPoint': {'lat': 21.30694, 'lon': -157.85833}}, {'zip': '60611', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Northwestern University CRS', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '60612', 'city': 'Chicago', 'state': 'Illinois', 'country': 'United States', 'facility': 'Cook County Hosp. CORE Ctr.', 'geoPoint': {'lat': 41.85003, 'lon': -87.65005}}, {'zip': '462025250', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'facility': 'Indiana Univ. School of Medicine, Infectious Disease Research Clinic', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}, {'zip': '46202', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'facility': 'Methodist Hosp. of Indiana', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}, {'zip': '21287', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins Adult AIDS CRS', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington U CRS', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'St. Louis ConnectCare, Infectious Diseases Clinic', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '13210', 'city': 'Buffalo', 'state': 'New York', 'country': 'United States', 'facility': 'SUNY - Buffalo, Erie County Medical Ctr.', 'geoPoint': {'lat': 42.88645, 'lon': -78.87837}}, {'zip': '10003', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Beth Israel Med. Ctr. (Mt. Sinai)', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'NY Univ. HIV/AIDS CRS', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '452670405', 'city': 'Cincinnati', 'state': 'Ohio', 'country': 'United States', 'facility': 'Univ. of Cincinnati CRS', 'geoPoint': {'lat': 39.12711, 'lon': -84.51439}}, {'zip': '432101228', 'city': 'Columbus', 'state': 'Ohio', 'country': 'United States', 'facility': 'The Ohio State Univ. AIDS CRS', 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}], 'overallOfficials': [{'name': 'Luft B', 'role': 'STUDY_CHAIR'}, {'name': 'Chirgwin K', 'role': 'STUDY_CHAIR'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Allergy and Infectious Diseases (NIAID)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}