Ignite Creation Date:
2025-12-24 @ 10:16 PM
Ignite Modification Date:
2025-12-31 @ 8:29 AM
Study NCT ID:
NCT00997035
Status:
COMPLETED
Last Update Posted:
2019-02-26
First Post:
2009-10-14
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
The Mycotic Ulcer Treatment Trial II: A Randomized Trial Comparing Oral Voriconazole vs Placebo
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003320', 'term': 'Corneal Ulcer'}, {'id': 'D015821', 'term': 'Eye Infections, Fungal'}, {'id': 'D009181', 'term': 'Mycoses'}, {'id': 'D005128', 'term': 'Eye Diseases'}], 'ancestors': [{'id': 'D015817', 'term': 'Eye Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D007634', 'term': 'Keratitis'}, {'id': 'D003316', 'term': 'Corneal Diseases'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D065819', 'term': 'Voriconazole'}], 'ancestors': [{'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'kathryn.ray@ucsf.edu', 'phone': '415-514-3227', 'title': 'Kathryn Ray', 'organization': 'University of California, San Francisco'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Over the entire course of the trial. (June, 2010-December 2015)', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'Placebo: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\nTwo tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.', 'otherNumAtRisk': 121, 'otherNumAffected': 27, 'seriousNumAtRisk': 121, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Oral Voriconazole', 'description': 'Voriconazole: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing \\<40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.', 'otherNumAtRisk': 119, 'otherNumAffected': 52, 'seriousNumAtRisk': 119, 'seriousNumAffected': 7}], 'otherEvents': [{'term': 'Ulcer not healing after 6 weeks of therapy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 5}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Increase in hypopyon (increase>2mm)', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 5}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 7}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'AST or ALT elevated to twice upper limit of normal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 8}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 5}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Visual disturbances', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 5}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Fever', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Lethargy', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Local allergic reaction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Other systemic event thought to be related to study drug', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Dermatologic reaction', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Stomach pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Endophthalmitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 3}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Evisceration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Myocardial infarction or stroke', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'AST or ALT elevated to five times the upper limit of normal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 121, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 119, 'numAffected': 2}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Incidence of Perforation or Therapeutic Penetrating Keratoplasty', 'denoms': [{'units': 'Participants', 'counts': [{'value': '119', 'groupId': 'OG000'}, {'value': '121', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'oral voriconazole plus topical antifungal agents'}, {'id': 'OG001', 'title': 'Oral Placebo', 'description': 'oral placebo plus topical antifungal agents'}], 'classes': [{'categories': [{'measurements': [{'value': '0.0095562', 'groupId': 'OG000'}, {'value': '0.011204', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.29', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.82', 'ciLowerLimit': '0.57', 'ciUpperLimit': '1.18', 'groupDescription': 'The sample size was determined based on the primary end point: perforation or the need for TPK within 3 months. Simulation-based analyses estimated that a sample sizeof 240 study participants (120 per arm) would provide 80% power to detect a 15% difference in the 3-month perforation or need for TPK rate between topical antifungal plus oral voriconazole vs topical antifungal alone,with a 2-tailed α value of .05 and approximately 15%loss to follow-up.', 'statisticalMethod': 'Regression, Cox', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Cox proportional hazards regression to estimate the hazard of perforation or need for TPK.'}], 'paramType': 'NUMBER', 'timeFrame': '3 months from enrollment', 'description': 'Hazard ratio of perforation or therapeutic penetrating keratoplasty (TPK) comparing voriconazole to placebo', 'unitOfMeasure': 'New perforations or TPK/person-days', 'reportingStatus': 'POSTED', 'populationDescription': 'Comparison of rate of perforation or TPK between the treatment groups (topical voriconazole with oral voriconazole vs. topical voriconazole with oral placebo)'}, {'type': 'SECONDARY', 'title': 'Best Spectacle-corrected logMAR Visual Acuity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '107', 'groupId': 'OG000'}, {'value': '100', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'Oral Voriconazole plus topical antifungal agents'}, {'id': 'OG001', 'title': 'Oral Placebo', 'description': 'Oral Placebo plus topical antifungal agents'}], 'classes': [{'categories': [{'measurements': [{'value': '.7852594', 'spread': '.1083858', 'groupId': 'OG000'}, {'value': '.787141', 'spread': '.1646131', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '3 months after enrollment', 'description': 'Best spectacle-corrected logMAR visual acuity at 3 months after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear', 'unitOfMeasure': 'logMAR', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Best spectacle-corrected logMAR visual acuity at 3 weeks after enrollment, adjusting for enrollment BSCVA and study site'}, {'type': 'SECONDARY', 'title': 'Best Spectacle-corrected logMAR Visual Acuity at 3-weeks', 'denoms': [{'units': 'Participants', 'counts': [{'value': '113', 'groupId': 'OG000'}, {'value': '112', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'Oral Voriconazole plus topical antifungal agents'}, {'id': 'OG001', 'title': 'Oral Placebo', 'description': 'Oral Placebo plus topical antifungal agents'}], 'classes': [{'categories': [{'measurements': [{'value': '.8745454', 'spread': '.1080198', 'groupId': 'OG000'}, {'value': '.744252', 'spread': '.0964871', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '3 weeks after enrollment', 'description': 'Best spectacle-corrected logMAR visual acuity at 3 weeks after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear', 'unitOfMeasure': 'logMAR', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Best spectacle-corrected logMAR visual acuity at 3 weeks after enrollment, adjusting for enrollment BSCVA and study site.'}, {'type': 'SECONDARY', 'title': 'Size of Infiltrate/Scar - 3 Months', 'denoms': [{'units': 'Participants', 'counts': [{'value': '107', 'groupId': 'OG000'}, {'value': '100', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'Oral voriconazole treated participants'}, {'id': 'OG001', 'title': 'Oral Placebo', 'description': 'Oral Placebo plus topical antifungal agents'}], 'classes': [{'categories': [{'measurements': [{'value': '.9319315', 'spread': '.06508', 'groupId': 'OG000'}, {'value': '.697005', 'spread': '.0927', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '3 months after enrollment', 'description': 'Size of infiltrate/scar at 3 months after enrollment, using enrollment infiltrate scar/size as a covariate', 'unitOfMeasure': 'mm^2', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Mean infiltrate scar size at three months correcting for baseline scar size and site'}, {'type': 'SECONDARY', 'title': 'Size of Infiltrate/Scar', 'denoms': [{'units': 'Participants', 'counts': [{'value': '113', 'groupId': 'OG000'}, {'value': '112', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'Oral voriconazole treated participants'}, {'id': 'OG001', 'title': 'Oral Placebo', 'description': 'Oral Placebo plus topical antifungal agent'}], 'classes': [{'categories': [{'measurements': [{'value': '.2192398', 'spread': '.1663', 'groupId': 'OG000'}, {'value': '.7973467', 'spread': '.073885', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '3 weeks after enrollment', 'description': 'Size of infiltrate/scar at 3 weeks after enrollment, using enrollment infiltrate scar/size as a covariate', 'unitOfMeasure': 'mm^2', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Mean infiltrate scar size at three weeks.'}, {'type': 'SECONDARY', 'title': 'Hazard Ratio for Re-epithelialization', 'denoms': [{'units': 'Participants', 'counts': [{'value': '113', 'groupId': 'OG000'}, {'value': '112', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'oral voriconazole plus topical antifungal'}, {'id': 'OG001', 'title': 'Oral Placebo', 'description': 'oral placebo plus topical antifungal'}], 'classes': [{'categories': [{'measurements': [{'value': '.0141123', 'groupId': 'OG000'}, {'value': '.0130862', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.65', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Hazard Ratio (HR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.87', 'ciLowerLimit': '.49', 'ciUpperLimit': '1.57', 'statisticalMethod': 'Regression, Cox', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'NUMBER', 'timeFrame': 'Up to 21 days', 'description': 'Hazard Ratio of re-epithelialization comparing the treatment groups', 'unitOfMeasure': 'Number re-epthelialized/person-days', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Microbiological Cure at 7 Days', 'denoms': [{'units': 'Participants', 'counts': [{'value': '121', 'groupId': 'OG000'}, {'value': '119', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Placebo: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\nTwo tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.'}, {'id': 'OG001', 'title': 'Oral Voriconazole', 'description': 'Voriconazole: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing \\<40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.'}], 'classes': [{'categories': [{'measurements': [{'value': '50', 'groupId': 'OG000'}, {'value': '50', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': '7 days', 'description': 'Fungal Culture negative at 7 days post treatment', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Fungal Culture negative at 7 days post treatment'}, {'type': 'SECONDARY', 'title': 'Number of Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '119', 'groupId': 'OG000'}, {'value': '121', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'Voriconazole: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing \\<40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\nTwo tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.'}], 'classes': [{'categories': [{'measurements': [{'value': '58', 'groupId': 'OG000'}, {'value': '28', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '<0.001', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'Statistically significant after Holms-Šidák correction for multiple comparisons.', 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'NUMBER', 'timeFrame': '3-months from enrollment', 'description': 'Comparing the number of serious and non-serious adverse events by treatment arm.', 'unitOfMeasure': 'adverse events', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Minimum Inhibitory Concentration of Isolates - Natamycin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '64', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'Voriconazole: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing \\<40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\nTwo tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.'}], 'classes': [{'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000', 'lowerLimit': '4', 'upperLimit': '32'}, {'value': '4', 'groupId': 'OG001', 'lowerLimit': '4', 'upperLimit': '16'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '7 days', 'description': 'Minimum Inhibitory Concentration (MIC) of isolates to natamycin by treatment arm', 'unitOfMeasure': 'mg/L', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Minimum Inhibitory Concentration of Isolates - Voriconazole', 'denoms': [{'units': 'Participants', 'counts': [{'value': '62', 'groupId': 'OG000'}, {'value': '64', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Oral Voriconazole', 'description': 'Voriconazole: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing \\<40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\nTwo tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000', 'lowerLimit': '0.5', 'upperLimit': '4'}, {'value': '2', 'groupId': 'OG001', 'lowerLimit': '0.5', 'upperLimit': '4'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '7 days', 'description': 'Minimum Inhibitory Concentration (MIC) of isolates to voriconazole by treatment arm', 'unitOfMeasure': 'mg/L', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo', 'description': 'Placebo: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\nTwo tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.'}, {'id': 'FG001', 'title': 'Oral Voriconazole', 'description': 'Voriconazole: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing \\<40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.'}], 'periods': [{'title': '3-week Followup Visit', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '121'}, {'groupId': 'FG001', 'numSubjects': '119'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '112'}, {'groupId': 'FG001', 'numSubjects': '113'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '6'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '6'}]}]}, {'title': '3-month Follow-up Visit', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '112'}, {'groupId': 'FG001', 'numSubjects': '113'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '100'}, {'groupId': 'FG001', 'numSubjects': '107'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '6'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '12'}, {'groupId': 'FG001', 'numSubjects': '6'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '121', 'groupId': 'BG000'}, {'value': '119', 'groupId': 'BG001'}, {'value': '240', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo', 'description': 'Placebo: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\nTwo tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.'}, {'id': 'BG001', 'title': 'Oral Voriconazole', 'description': 'Voriconazole: 1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing \\<40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '98', 'groupId': 'BG000'}, {'value': '93', 'groupId': 'BG001'}, {'value': '191', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '50', 'groupId': 'BG000', 'lowerLimit': '45', 'upperLimit': '60'}, {'value': '54', 'groupId': 'BG001', 'lowerLimit': '42', 'upperLimit': '62'}, {'value': '54', 'groupId': 'BG002', 'lowerLimit': '45', 'upperLimit': '60'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '50', 'groupId': 'BG000'}, {'value': '54', 'groupId': 'BG001'}, {'value': '104', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '71', 'groupId': 'BG000'}, {'value': '65', 'groupId': 'BG001'}, {'value': '136', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Nepal', 'categories': [{'measurements': [{'value': '98', 'groupId': 'BG000'}, {'value': '98', 'groupId': 'BG001'}, {'value': '196', 'groupId': 'BG002'}]}]}, {'title': 'India', 'categories': [{'measurements': [{'value': '23', 'groupId': 'BG000'}, {'value': '21', 'groupId': 'BG001'}, {'value': '44', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Weight (lbs)', 'classes': [{'categories': [{'measurements': [{'value': '108', 'groupId': 'BG000', 'lowerLimit': '97', 'upperLimit': '121'}, {'value': '105', 'groupId': 'BG001', 'lowerLimit': '94', 'upperLimit': '123'}, {'value': '108', 'groupId': 'BG002', 'lowerLimit': '97', 'upperLimit': '121'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'lbs', 'dispersionType': 'INTER_QUARTILE_RANGE'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 240}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-02', 'completionDateStruct': {'date': '2016-03', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-02-04', 'studyFirstSubmitDate': '2009-10-14', 'resultsFirstSubmitDate': '2016-06-09', 'studyFirstSubmitQcDate': '2009-10-15', 'lastUpdatePostDateStruct': {'date': '2019-02-26', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-05-17', 'studyFirstPostDateStruct': {'date': '2009-10-16', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2017-06-14', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Incidence of Perforation or Therapeutic Penetrating Keratoplasty', 'timeFrame': '3 months from enrollment', 'description': 'Hazard ratio of perforation or therapeutic penetrating keratoplasty (TPK) comparing voriconazole to placebo'}], 'secondaryOutcomes': [{'measure': 'Best Spectacle-corrected logMAR Visual Acuity', 'timeFrame': '3 months after enrollment', 'description': 'Best spectacle-corrected logMAR visual acuity at 3 months after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear'}, {'measure': 'Best Spectacle-corrected logMAR Visual Acuity at 3-weeks', 'timeFrame': '3 weeks after enrollment', 'description': 'Best spectacle-corrected logMAR visual acuity at 3 weeks after enrollment, adjusting for enrollment BSCVA and treatment arm in a multiple linear'}, {'measure': 'Size of Infiltrate/Scar - 3 Months', 'timeFrame': '3 months after enrollment', 'description': 'Size of infiltrate/scar at 3 months after enrollment, using enrollment infiltrate scar/size as a covariate'}, {'measure': 'Size of Infiltrate/Scar', 'timeFrame': '3 weeks after enrollment', 'description': 'Size of infiltrate/scar at 3 weeks after enrollment, using enrollment infiltrate scar/size as a covariate'}, {'measure': 'Hazard Ratio for Re-epithelialization', 'timeFrame': 'Up to 21 days', 'description': 'Hazard Ratio of re-epithelialization comparing the treatment groups'}, {'measure': 'Microbiological Cure at 7 Days', 'timeFrame': '7 days', 'description': 'Fungal Culture negative at 7 days post treatment'}, {'measure': 'Number of Adverse Events', 'timeFrame': '3-months from enrollment', 'description': 'Comparing the number of serious and non-serious adverse events by treatment arm.'}, {'measure': 'Minimum Inhibitory Concentration of Isolates - Natamycin', 'timeFrame': '7 days', 'description': 'Minimum Inhibitory Concentration (MIC) of isolates to natamycin by treatment arm'}, {'measure': 'Minimum Inhibitory Concentration of Isolates - Voriconazole', 'timeFrame': '7 days', 'description': 'Minimum Inhibitory Concentration (MIC) of isolates to voriconazole by treatment arm'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Fungal Infections', 'Eye Disease', 'Fungal Keratitis', 'Visual Acuity'], 'conditions': ['Corneal Ulcer', 'Eye Infections, Fungal']}, 'referencesModule': {'references': [{'pmid': '40372030', 'type': 'DERIVED', 'citation': 'Zegans ME, Kamath MM, Jones JT, Bao R, Ross BS, Gutierrez-Perez C, Adams EM, Lightfoot JD, Poimenidou G, Pavuluri C, Prajna V, Cramer RA, Fuller KK. Propranolol is efficacious against Aspergillus and Fusarium corneal isolates in vitro and in a murine model of Aspergillus keratitis. Antimicrob Agents Chemother. 2025 Jun 4;69(6):e0166424. doi: 10.1128/aac.01664-24. Epub 2025 May 15.'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to determine if the addition of oral voriconazole to topical treatment regimens results in lower rates of perforation in severe fungal corneal ulcers.', 'detailedDescription': 'Fungal corneal ulcers tend to have very poor outcomes with commonly used treatments. There has only been a single randomized trial of anti-fungal therapy for mycotic keratitis, and no new ocular anti-fungal medications have been approved by the FDA since the 1960s. The triazole voriconazole has recently become the treatment of choice for systemic fungal infections such as pulmonary aspergillosis. The use of topical ophthalmic preparations of voriconazole has been described in numerous case reports, however there has been no systematic attempt to determine whether it is more or less clinically effective than natamycin. Additionally, there have been many case reports of the use of oral voriconazole in the treatment of fungal corneal ulcers, however there has been no systematic attempt to determine if it improves outcomes in severe ulcers.\n\nThis study is a randomized, double-masked, placebo-controlled trial to determine if the use of oral voriconazole in severe ulcers reduces the rate of perforations. 240 fungal corneal ulcers with baseline visual acuity worse than 6/120 presenting to the Aravind Eye Hospitals and the UCSF Proctor Foundation will be randomized to receive oral voriconazole plus topical voriconazole and topical natamycin, or oral placebo plus topical voriconazole and topical natamycin. The primary outcome is the rate of perforation over the three month follow-up period.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '16 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Presence of a corneal ulcer at presentation\n* Evidence of filamentous fungus on smear (KOH wet mount, Giemsa, or Gram stain)\n* Visual acuity worse than 6/120 (20/400, logMAR 1.3)\n* The patient must be able to verbalize a basic understanding of the study after it is explained to the patient, as determined by physician examiner. This understanding must include a commitment to return for follow-up visits.\n* Willingness to be treated as an inpatient or to be treated as an outpatient and return every 3 days +/- 1 day until re-epithelialization and every week to receive fresh medication for 3 weeks\n* Appropriate consent\n\nExclusion Criteria:\n\n* Evidence of bacteria on Gram stain at the time of enrollment\n* Evidence of acanthamoeba by stain\n* Evidence of herpetic keratitis by history or exam\n* Corneal scar not easily distinguishable from current ulcer\n* Age less than 16 years (before 16th birthday)\n* Bilateral ulcers\n* Previous penetrating keratoplasty in the affected eye\n* Pregnancy (by history or urine test) or breast feeding (by history)\n* Known liver disease, including hepatitis or cirrhosis (Child-Pugh A-C)\n* Acuity worse than 6/60 (2/200) in the fellow eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA 6/60 or better qualifies for enrollment)\n* Acuity better than 6/120 (20/400) in the study eye (note that any acuity, uncorrected, corrected, pinhole, or BSCVA can be used for enrollment)\n* Currently on rifampin, rifabutin, ritonavir, long acting barbiturates, phenytoin, carbamazepine, or other drugs known to interact with voriconazole\n* Known allergy to study medications (antifungal or preservative)\n* No light perception in the affected eye\n* Not willing to participate'}, 'identificationModule': {'nctId': 'NCT00997035', 'acronym': 'MUTTII', 'briefTitle': 'The Mycotic Ulcer Treatment Trial II: A Randomized Trial Comparing Oral Voriconazole vs Placebo', 'organization': {'class': 'OTHER', 'fullName': 'University of California, San Francisco'}, 'officialTitle': 'The Mycotic Ulcer Treatment Trial II: A Randomized Trial Comparing Oral Voriconazole vs Placebo', 'orgStudyIdInfo': {'id': 'H9332-33965-02_2'}, 'secondaryIdInfos': [{'id': 'U10EY018573', 'link': 'https://reporter.nih.gov/quickSearch/U10EY018573', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Oral Voriconazole', 'interventionNames': ['Drug: Voriconazole']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Voriconazole', 'type': 'DRUG', 'description': '1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n400 mg BID PO on study day one (loading dose), then 200 mg BID PO until 3 weeks from enrollment for patients weighing greater than 50 kg. For patients 40-50 kg, the loading dose is 300 mg BID PO on study day 1, then 150 mg BID PO until 3 weeks from enrollment. For patients weighing \\<40 kg, the loading dose is 200 mg BID PO, then 100 mg BID PO until 3 weeks after enrollment.', 'armGroupLabels': ['Oral Voriconazole']}, {'name': 'Placebo', 'type': 'DRUG', 'description': '1% voriconazole (topical) plus 0.01% preservative, 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\n5% natamycin (topical), 1 drop applied to the affected eye every one hour while awake for 1 week, then every 2 hours while awake until three weeks after enrollment.\n\nTwo tablets BID PO on study day one, then one tablet BID PO until 3 weeks from enrollment.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '94143', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'Proctor Foundation, UCSF', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'city': 'Coimbatore', 'state': 'Tamil Nadu', 'country': 'India', 'facility': 'Aravind Eye Hospital', 'geoPoint': {'lat': 11.00555, 'lon': 76.96612}}, {'city': 'Madurai', 'state': 'Tamil Nadu', 'country': 'India', 'facility': 'Aravind Eye Hospitals', 'geoPoint': {'lat': 9.919, 'lon': 78.11953}}, {'city': 'Pondicherry', 'state': 'Tamil Nadu', 'country': 'India', 'facility': 'Aravind Eye Hospital'}, {'city': 'Tirunelveli', 'state': 'Tamil Nadu', 'country': 'India', 'facility': 'Aravind Eye Hospital', 'geoPoint': {'lat': 8.72742, 'lon': 77.6838}}, {'city': 'Bharatpur', 'state': 'Chitwan', 'country': 'Nepal', 'facility': 'Bharatpur Eye Hospital', 'geoPoint': {'lat': 27.6768, 'lon': 84.43589}}, {'city': 'Siddharthanagar', 'state': 'Lumbini', 'country': 'Nepal', 'facility': 'Lumbini Eye Institute', 'geoPoint': {'lat': 27.5, 'lon': 83.45}}], 'overallOfficials': [{'name': 'NV Prajna, DNB, FRC Ophth', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Aravind Eye Hospitals'}, {'name': 'Nisha Acharya, MD, MS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Proctor Foundation, UCSF'}, {'name': 'Tom Lietman, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Proctor Foundation, UCSF'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of California, San Francisco', 'class': 'OTHER'}, 'collaborators': [{'name': 'Aravind Eye Hospitals, India', 'class': 'OTHER'}, {'name': 'Dartmouth-Hitchcock Medical Center', 'class': 'OTHER'}, {'name': 'Lumbini Eye Institute and Research Centre', 'class': 'OTHER'}, {'name': 'Bharatpur Eye Hospital', 'class': 'OTHER'}, {'name': 'National Eye Institute (NEI)', 'class': 'NIH'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor in Residence', 'investigatorFullName': 'Thomas M. Lietman', 'investigatorAffiliation': 'University of California, San Francisco'}}}}