Ignite Creation Date:
2025-12-24 @ 5:30 PM
Ignite Modification Date:
2026-02-22 @ 4:52 PM
Study NCT ID:
NCT02863068
Status:
TERMINATED
Last Update Posted:
2025-05-07
First Post:
2016-05-16
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2025-03-25', 'type': 'ACTUAL'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D000755', 'term': 'Anemia, Sickle Cell'}, {'id': 'D014456', 'term': 'Ulcer'}], 'ancestors': [{'id': 'D000745', 'term': 'Anemia, Hemolytic, Congenital'}, {'id': 'D000743', 'term': 'Anemia, Hemolytic'}, {'id': 'D000740', 'term': 'Anemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D006453', 'term': 'Hemoglobinopathies'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D012977', 'term': 'Sodium Nitrite'}], 'ancestors': [{'id': 'D009573', 'term': 'Nitrites'}, {'id': 'D009608', 'term': 'Nitrous Acid'}, {'id': 'D017672', 'term': 'Nitrogen Compounds'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D017670', 'term': 'Sodium Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'bloodconsultant@gmail.com', 'phone': '240-498-8684', 'title': 'Dr. Caterina Minniti', 'organization': 'Albert Einstein College of Medicine'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Due to the early termination of the study, enrollment in the clinical trial did not reach the target number of participants needed to produce statistically reliable results.'}}, 'adverseEventsModule': {'timeFrame': 'Up to 10 weeks', 'eventGroups': [{'id': 'EG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 9, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 4}, {'id': 'EG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.', 'otherNumAtRisk': 8, 'deathsNumAtRisk': 8, 'otherNumAffected': 4, 'seriousNumAtRisk': 8, 'deathsNumAffected': 0, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'Vaso-occlusive Crisis', 'notes': 'Verbatim Terms: Sickle cell pain/Vaso-occlusive crisis/Ulcer Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 3}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Chest Wall Pain', 'notes': 'Left-sided', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Upper Respiratory Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Hyperkalemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Ulcer Infection', 'notes': 'Verbatim Terms: Wound Infection or Ulcer Infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Back Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Abnormal Blood Smear', 'notes': 'Laboratory result indicating blast on Complete Blood Count (CBC) report', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Critical Low Lab Value', 'notes': 'Verbatim Term cited', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Palpitations', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Abdominal Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Body Ache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}], 'seriousEvents': [{'term': 'Vaso-occlusive Crisis', 'notes': 'Sickle cell pain/Vaso-occlusive pain noted in all Topical Sodium Nitrite patients and 2 of 3 Placebo patients (other patient documented with nonspecific Pain, hospitalization indicated).', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numEvents': 4, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 7, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Ulcer Infection', 'notes': 'Verbatim Term: Wound Infection. Hospitalization indicated', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}, {'term': 'Acute Myeloid Leukemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 10, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE (4.0)'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Assessment of Tolerability (Methemoglobin Level)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'OG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.05', 'groupId': 'OG000', 'lowerLimit': '-0.6', 'upperLimit': '0.4'}, {'value': '0.25', 'groupId': 'OG001', 'lowerLimit': '-0.3', 'upperLimit': '0.4'}]}]}], 'analyses': [{'pValue': '0.2967', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in methemoglobin at baseline and EOS for all participants between treatment arms using a Wilcoxon signed rank test', 'groupDescription': 'Change in methemoglobin from baseline to end of study (EOS) for all participants.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline through last available measurement, up to 10 weeks', 'description': 'Assessment of tolerability was determined by evaluating the change in methemoglobin level from baseline through the end of study at week 10. Samples were collected and Methemoglobin levels were measured by co-oximetry Results are summarized by study arm using basic descriptive statistics and expressed as a percentage of the total hemoglobin in the sample.', 'unitOfMeasure': 'percentage of total hemoglobin', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.'}, {'type': 'PRIMARY', 'title': 'Change in Total Ulcerated Surface Area', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'OG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.50', 'groupId': 'OG000', 'lowerLimit': '-3.90', 'upperLimit': '-0.068'}, {'value': '-3.26', 'groupId': 'OG001', 'lowerLimit': '-12.0', 'upperLimit': '0.987'}]}]}], 'analyses': [{'pValue': '0.2818', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in total ulcerated surface area at baseline and EOS between treatment arms using a Wilcoxon signed rank test', 'groupDescription': 'Change in total ulcerated surface area from baseline to end of study (EOS)', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '1.0', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'Difference in frequency of 25% total ulcerated surface area reduction between treatment arms', 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': "Fisher's exact test was used to test for differences in frequencies between treatment arms"}], 'paramType': 'MEDIAN', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Change in total ulcerated surface area from baseline was assessed through the last study visit at 10 weeks. Surface area measurements of the ulcer were obtained and photographed with defined lighting, distance, exposure, and camera type. Total ulcerated surface area measurements were obtained using digital planimetry and measuring the longest length and widest width of the ulcer(s). Results are summarized by study arm using basic descriptive statistics and reported in cm\\^2. Negative results are indicative of a reduction in group median total ulcerated surface area from baseline and positive results are indicative of an increase in group median total ulcerated surface area from baseline.', 'unitOfMeasure': 'cm^2', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.'}, {'type': 'PRIMARY', 'title': 'Change in Ulcer Pain', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'OG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.5', 'groupId': 'OG000', 'lowerLimit': '-2.7', 'upperLimit': '1.2'}, {'value': '0.9', 'groupId': 'OG001', 'lowerLimit': '-3.8', 'upperLimit': '2.6'}]}]}], 'analyses': [{'pValue': '0.3754', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in average pain at baseline and EOS between treatment arms using a Wilcoxon signed rank test', 'groupDescription': 'Change in average pain from baseline to end of study (EOS)', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Change in Ulcer Pain from baseline through the last study visit at 10 weeks were assessed using the Visual Analog Scale (VAS). The VAS is a widely used tool to quantify subjective pain perception over time and in this study was used to determine the efficacy of the topical sodium nitrite. Participants were asked to mark a point on a line indicating the severity of their pain on a 0-10 scale, with "0" representing "No pain" and "10" representing the "Worst possible pain." A decrease in VAS score is indicative of a reduction in ulcer pain. Scores were summarized by study arm using basic descriptive statistics.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.'}, {'type': 'PRIMARY', 'title': 'Number of Participants With Total Ulcerated Surface Area Reduction', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'OG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}], 'classes': [{'title': 'No', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}, {'title': 'Yes', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'The number of participants who achieved an objective reduction in total surface area of the ulcer of \\>= 25% from baseline is summarized and reported as a dichotomous ("No" or "Yes") variable.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.'}, {'type': 'SECONDARY', 'title': 'Hydroxyurea Effect on Assessment of Tolerability', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'OG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}], 'classes': [{'title': 'HU', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-0.6', 'groupId': 'OG000', 'lowerLimit': '-0.7', 'upperLimit': '-0.4'}, {'value': '0.2', 'groupId': 'OG001', 'lowerLimit': '0', 'upperLimit': '0.3'}]}]}, {'title': 'No HU', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.3', 'groupId': 'OG000', 'lowerLimit': '0', 'upperLimit': '0.5'}, {'value': '0.3', 'groupId': 'OG001', 'lowerLimit': '-0.6', 'upperLimit': '0.5'}]}]}], 'analyses': [{'pValue': '0.1165', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in methemoglobin at baseline and EOS between treatment arms for participants on Hydroxyurea (HU) using a Wilcoxon signed rank test.', 'groupDescription': 'Change in methemoglobin from baseline to end of study (EOS) for participants on Hydroxyurea (HU).', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.4583', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in methemoglobin at baseline and EOS between treatment arms for participants off Hydroxyurea (HU) using a Wilcoxon signed rank test.', 'groupDescription': 'Change in methemoglobin from baseline to end of study (EOS) for participants off Hydroxyurea (HU).', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Hydroxyurea effect on Assessment of Tolerability, as determined by the change in Methemoglobin level, was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Samples were collected and Methemoglobin levels were measured by co-oximetry. Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized as an increased or decreased percentage by study arm and analyzed using Wilcoxon-Mann-Whitney statistical testing.', 'unitOfMeasure': 'percentage of total hemoglobin', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Number of participants analyzed identified in table below. For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.'}, {'type': 'SECONDARY', 'title': 'Hydroxyurea Effect on Change in Total Ulcerated Surface Area', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'OG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}], 'classes': [{'title': 'HU', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-1.34', 'groupId': 'OG000', 'lowerLimit': '-1.592', 'upperLimit': '-0.068'}, {'value': '-3.506', 'groupId': 'OG001', 'lowerLimit': '-6.97', 'upperLimit': '-3.013'}]}]}, {'title': 'No HU', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-2.081', 'groupId': 'OG000', 'lowerLimit': '-3.897', 'upperLimit': '-1.412'}, {'value': '-0.57', 'groupId': 'OG001', 'lowerLimit': '-17.04', 'upperLimit': '2.031'}]}]}], 'analyses': [{'pValue': '0.068', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in total ulcerated surface area at baseline and EOS between treatment arms for participants on Hydroxyurea (HU) using a Wilcoxon signed rank test.', 'groupDescription': 'Change in total ulcerated surface area from baseline to end of study (EOS) for participants on Hydroxyurea (HU).', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.5', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in total ulcerated surface area at baseline and EOS between treatment arms for participants off Hydroxyurea (HU) using a Wilcoxon signed rank test.', 'groupDescription': 'Change in total ulcerated surface area from baseline to end of study (EOS) for participants off Hydroxyurea (HU).', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '1.0', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'Difference in frequency of 25% total ulcerated surface area reduction between treatment arms for participants on Hydroxyurea (HU).', 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Difference in frequency of 25% total ulcerated surface area reduction between treatment arms for participants on Hydroxyurea (HU).'}, {'pValue': '1.0', 'groupIds': ['OG000', 'OG001'], 'groupDescription': 'Difference in frequency of 25% total ulcerated surface area reduction between treatment arms for participants off Hydroxyurea (HU).', 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': "Fisher's exact test was used to test for differences in frequencies between treatment arms for participants off Hydroxyurea (HU)."}], 'paramType': 'MEDIAN', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Hydroxyurea effect on Change in Total Ulcerated Surface Area was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Surface area measurements of the ulcer were obtained and photographed with defined lighting, distance, exposure, and camera type. Total ulcerated surface area measurements were obtained using digital planimetry and measuring the longest length and widest width of the ulcer(s). Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized by study arm as an increase or decrease in total ulcerated surface area in cm\\^2 and analyzed using Wilcoxon-Mann-Whitney and Fisher Exact statistical testing. Negative results are indicative of a reduction in group median total ulcerated surface area from baseline and positive results are indicative of an increase in group median total ulcerated surface area from baseline (with or without Hydroxyurea).', 'unitOfMeasure': 'cm^2', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Number of participants analyzed identified in table below. For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.'}, {'type': 'SECONDARY', 'title': 'Hydroxyurea Effect on Change in Ulcer Pain', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'OG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}], 'classes': [{'title': 'HU', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.35', 'groupId': 'OG000', 'lowerLimit': '-1.25', 'upperLimit': '2.10'}, {'value': '0.9', 'groupId': 'OG001', 'lowerLimit': '-5.0', 'upperLimit': '2.4'}]}]}, {'title': 'No HU', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '5', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-2.70', 'groupId': 'OG000', 'lowerLimit': '-4.0', 'upperLimit': '0.0'}, {'value': '1.0', 'groupId': 'OG001', 'lowerLimit': '-2.2', 'upperLimit': '4.1'}]}]}], 'analyses': [{'pValue': '0.4298', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in average pain at baseline and EOS between treatment arms for participants on Hydroxyurea (HU) using a Wilcoxon signed rank test.', 'groupDescription': 'Change in average pain from baseline to end of study (EOS) for participants on Hydroxyurea (HU).', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.2701', 'groupIds': ['OG000', 'OG001'], 'pValueComment': 'A matched pairs design was employed to test for changes in average pain at baseline and EOS between treatment arms for participants off Hydroxyurea (HU) using a Wilcoxon signed rank test.', 'groupDescription': 'Change in average pain from baseline to end of study (EOS) for participants off Hydroxyurea (HU).', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Hydroxyurea effect on change in Ulcer Pain was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Ulcer pain assessments were conducted using the Visual Analog Scale (VAS). The VAS is used to quantify subjective pain perception over time and in this study was used to determine the efficacy of the topical sodium nitrite. Participants were asked to mark a point on a line indicating the severity of their pain on a 0-10 scale, with "0" representing "No pain" and "10" representing the "Worst possible pain." Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized by study arm as an increase or decrease in ulcer pain and analyzed using Wilcoxon-Mann-Whitney statistical testing. Negative results are indicative of a decrease in group median ulcer pain from baseline and positive results are indicative of an increase in group median ulcer pain from baseline (with or without Hydroxyurea).', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Number of participants analyzed identified in table below. For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'FG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '8'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '8'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': '26 patients (pts) were screened and 24 consented (one was consented twice as the IRB required a reconsent due to the time interval which had lapsed between the consent process and study initiation during COVID). Of the 24 unique pts, 2 were lost to follow up during the run-in period and 4 pts had a reduction in ulcer size by \\>25%, via normal wound care, during the run-in period and were not eligible for study-defined treatment and not enrolled into the study. As such, 18 pts were enrolled.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Placebo', 'description': 'Participants will receive placebo and standard of care\n\nPlacebo: Participants will have Placebo applied to total ulcerated area. If a participant has more than one ulcer, all of them will be treated with placebo in this intervention.'}, {'id': 'BG001', 'title': 'Topical Sodium Nitrite', 'description': 'Participants will receive 2% topical sodium nitrite cream and standard of care\n\nTopical Sodium Nitrite: Participants will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm\\^2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm\\^2. If a participant has more than one ulcer, all of them will be treated with either "study cream" in this intervention.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '40.2', 'spread': '11.0', 'groupId': 'BG000'}, {'value': '47.6', 'spread': '13.8', 'groupId': 'BG001'}, {'value': '43.5', 'spread': '12.5', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '12', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Total Ulcerated Surface Area', 'classes': [{'categories': [{'measurements': [{'value': '11.4', 'spread': '12.3', 'groupId': 'BG000'}, {'value': '16.6', 'spread': '15.4', 'groupId': 'BG001'}, {'value': '13.7', 'spread': '13.6', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Surface area measurements of the ulcer(s) were obtained and photographed with defined lighting, distance, exposure, and camera type. Total ulcerated surface area measurements were obtained using digital planimetry and measuring the longest length and widest width of the ulcer. Results are summarized by study arm using basic descriptive statistics and reported in cm\\^2.', 'unitOfMeasure': 'cm^2', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sickle Cell Genotype', 'classes': [{'title': 'HbSS', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}]}, {'title': 'HbSB+', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'HbSC', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}, {'title': 'HbSD', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}, {'title': 'HbS/O (Arab)', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Sickle cell genotype confirmation was confirmed by hemoglobin electrophoresis analysis at baseline or patient charts. Participants were categorized as either:\n\nHbSS: Homozygous sickle cell disease, considered the most severe form; HbSB+: Hemoglobin S-beta thalassemia, a compound heterozygous condition considered a milder form; HbSC: 2nd most common variant and a milder form; HbSD: a double heterozygous state of two mutant alleles; or HbS/O(Arab): a rare compound heterozygous variant\n\nThe number/percentage of each genotype is summarized and reported by study arm.', 'unitOfMeasure': 'Participants'}, {'title': 'Hydroxyurea Usage', 'classes': [{'title': 'No', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}]}, {'title': 'Yes', 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'The number/percentage of participants actively using Hydroxyurea (a disease-modifying agent) at baseline was evaluated. Hydroxyurea usage was confirmed and reported using a dichotomous "Yes" or "No" assessment.', 'unitOfMeasure': 'Participants'}, {'title': 'Methemoglobin Levels', 'classes': [{'categories': [{'measurements': [{'value': '1.76', 'spread': '0.635', 'groupId': 'BG000'}, {'value': '1.49', 'spread': '0.698', 'groupId': 'BG001'}, {'value': '1.64', 'spread': '0.658', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Samples were collected and analyzed by co-oximetry to determine Methemoglobin (metHb) levels in order to exclude participants with congenital methemoglobinemia. Patients who had at least two documented metHb levels below the 3.5% threshold continued the study even if the meth Hb levels elevated above 3.5% during the weeks leading to the first application, as long as they remain below 4.5%. Baseline results are summarized by study arm using basic descriptive statistics and results were expressed as a percentage of the total hemoglobin in the sample.', 'unitOfMeasure': 'percentage of total hemoglobin', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Visual Analog Scale (VAS) for Pain Intensity', 'classes': [{'categories': [{'measurements': [{'value': '5.3', 'spread': '2.49', 'groupId': 'BG000'}, {'value': '4.28', 'spread': '1.62', 'groupId': 'BG001'}, {'value': '4.84', 'spread': '2.15', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'The Visual Analog Scale (VAS) was used to assess existing pain intensity prior to the initiation of treatment. The VAS is a pain intensity scale that uses a 10-centimeter (cm) line where 0 represents "No pain" and 10 represents "Worst possible pain." Participants were asked to mark current pain levels on the line and the distance from the "No pain" end of the line measured in cm was used to determine a VAS score. VAS scores were summarized by study arm/group using basic descriptive statistics. Higher scores were associated with greater overall pain intensity.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'STANDARD_DEVIATION'}], 'populationDescription': 'For this study, the fundamental analysis unit was the participant and not the ulcer(s). All data is presented accordingly.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2019-11-06', 'size': 7569508, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2025-02-27T15:50', 'hasProtocol': True}, {'date': '2022-07-20', 'size': 214133, 'label': 'Informed Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-02-02T15:31', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'whyStopped': 'Study terminated prior to achieving target enrollment due to slow recruitment and high cost of obtaining new study drug. Since no additional funds were to be available due to end of the funding period, remaining funds were expended on analyses.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2018-04-06', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2023-11-24', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-05-06', 'studyFirstSubmitDate': '2016-05-16', 'resultsFirstSubmitDate': '2025-02-28', 'studyFirstSubmitQcDate': '2016-08-08', 'lastUpdatePostDateStruct': {'date': '2025-05-07', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2025-05-06', 'studyFirstPostDateStruct': {'date': '2016-08-11', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2025-05-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-11-24', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Assessment of Tolerability (Methemoglobin Level)', 'timeFrame': 'Baseline through last available measurement, up to 10 weeks', 'description': 'Assessment of tolerability was determined by evaluating the change in methemoglobin level from baseline through the end of study at week 10. Samples were collected and Methemoglobin levels were measured by co-oximetry Results are summarized by study arm using basic descriptive statistics and expressed as a percentage of the total hemoglobin in the sample.'}, {'measure': 'Change in Total Ulcerated Surface Area', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Change in total ulcerated surface area from baseline was assessed through the last study visit at 10 weeks. Surface area measurements of the ulcer were obtained and photographed with defined lighting, distance, exposure, and camera type. Total ulcerated surface area measurements were obtained using digital planimetry and measuring the longest length and widest width of the ulcer(s). Results are summarized by study arm using basic descriptive statistics and reported in cm\\^2. Negative results are indicative of a reduction in group median total ulcerated surface area from baseline and positive results are indicative of an increase in group median total ulcerated surface area from baseline.'}, {'measure': 'Change in Ulcer Pain', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Change in Ulcer Pain from baseline through the last study visit at 10 weeks were assessed using the Visual Analog Scale (VAS). The VAS is a widely used tool to quantify subjective pain perception over time and in this study was used to determine the efficacy of the topical sodium nitrite. Participants were asked to mark a point on a line indicating the severity of their pain on a 0-10 scale, with "0" representing "No pain" and "10" representing the "Worst possible pain." A decrease in VAS score is indicative of a reduction in ulcer pain. Scores were summarized by study arm using basic descriptive statistics.'}, {'measure': 'Number of Participants With Total Ulcerated Surface Area Reduction', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'The number of participants who achieved an objective reduction in total surface area of the ulcer of \\>= 25% from baseline is summarized and reported as a dichotomous ("No" or "Yes") variable.'}], 'secondaryOutcomes': [{'measure': 'Hydroxyurea Effect on Assessment of Tolerability', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Hydroxyurea effect on Assessment of Tolerability, as determined by the change in Methemoglobin level, was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Samples were collected and Methemoglobin levels were measured by co-oximetry. Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized as an increased or decreased percentage by study arm and analyzed using Wilcoxon-Mann-Whitney statistical testing.'}, {'measure': 'Hydroxyurea Effect on Change in Total Ulcerated Surface Area', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Hydroxyurea effect on Change in Total Ulcerated Surface Area was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Surface area measurements of the ulcer were obtained and photographed with defined lighting, distance, exposure, and camera type. Total ulcerated surface area measurements were obtained using digital planimetry and measuring the longest length and widest width of the ulcer(s). Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized by study arm as an increase or decrease in total ulcerated surface area in cm\\^2 and analyzed using Wilcoxon-Mann-Whitney and Fisher Exact statistical testing. Negative results are indicative of a reduction in group median total ulcerated surface area from baseline and positive results are indicative of an increase in group median total ulcerated surface area from baseline (with or without Hydroxyurea).'}, {'measure': 'Hydroxyurea Effect on Change in Ulcer Pain', 'timeFrame': 'From Baseline through last study visit at 10 weeks', 'description': 'Hydroxyurea effect on change in Ulcer Pain was conducted to evaluate the effect of hydroxyurea in combination with the topical sodium nitrite or placebo. Ulcer pain assessments were conducted using the Visual Analog Scale (VAS). The VAS is used to quantify subjective pain perception over time and in this study was used to determine the efficacy of the topical sodium nitrite. Participants were asked to mark a point on a line indicating the severity of their pain on a 0-10 scale, with "0" representing "No pain" and "10" representing the "Worst possible pain." Study outcomes between participants with use of ("HU") and non-use of ("No HU") hydroxyurea are summarized by study arm as an increase or decrease in ulcer pain and analyzed using Wilcoxon-Mann-Whitney statistical testing. Negative results are indicative of a decrease in group median ulcer pain from baseline and positive results are indicative of an increase in group median ulcer pain from baseline (with or without Hydroxyurea).'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Sickle cell disease', 'sodium nitrite', 'wound healing', 'Ulcer'], 'conditions': ['Sickle Cell Disease']}, 'referencesModule': {'references': [{'pmid': '25938131', 'type': 'BACKGROUND', 'citation': 'Minniti CP, Gorbach AM, Xu D, Hon YY, Delaney KM, Seidel M, Malik N, Peters-Lawrence M, Cantilena C, Nichols JS, Mendelsohn L, Conrey A, Grimes G, Kato GJ. Topical sodium nitrite for chronic leg ulcers in patients with sickle cell anaemia: a phase 1 dose-finding safety and tolerability trial. Lancet Haematol. 2014 Dec 1;1(3):e95-e103. doi: 10.1016/s2352-3026(14)00019-2.'}]}, 'descriptionModule': {'briefSummary': 'The investigators are conducting a Phase II prospective and placebo controlled study of a topical cream containing sodium nitrite compared to the current standard of care. Sodium nitrite is a local donor of nitric oxide, which is known to improve blood flow and decrease bacterial load in the ulcer bed. The primary objectives are to evaluate the safety of topical sodium nitrite cream treatment in patients with sickle cell disease and chronic leg ulcers and to determine its effectiveness in accelerating the healing process and decreasing the pain associated with ulceration.\n\nPotential benefit will be a durable resolution or improvement of the leg ulcer and its associated pain. Possible side effects include decreased blood pressure and methemoglobinemia, secondary to sodium nitrite absorption through the ulcerated skin.\n\nFunding source FDA OOPD.', 'detailedDescription': 'Chronic leg ulcers are a complication of many blood disorders such as sickle cell disease, thalassemia, and other red blood cell disorders. In these disorders, red blood cells break down earlier than normal, which researchers suspect may cause or contribute to the development of leg ulcers; however, the exact cause is unknown, and current therapies are not very effective. Researchers are interested in determining if a research cream made with sodium nitrite, a substance that is known to increase blood flow by dilating blood vessels, may speed up the healing of skin ulcers.\n\nInvestigators are planning to enroll fifty patients with sickle cell disease to be randomized and treated twice a week with sodium nitrite cream or a placebo for ten weeks. The following events will be compared in treatment and placebo arms: a) changes in blood pressure; b) changes in pulse oximetry; c) changes in methemoglobin levels; d) any adverse events; e) rate of sickle cell disease (SCD) related complications; f) changes in biomarkers of inflammation and other laboratory data such as complete blood count and chemistries.\n\nIn order to determine if topical sodium nitrite accelerates wound healing and decreases pain at the wound site compared to placebo in patients receiving similar levels of wound care, investigators will a) accurately measure and photograph ulcers at baseline, after a two week run-in period and at predefined time points during the study and compare treatment arm to placebo; b) pain scores at wound sites will be recorded and compared for the two groups, c) Investigators will calculate opioid intake in the two arms and d) quality of life measures before and at the end of the trial'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Subjects must have a diagnosis of sickle cell disease (SS, SC, Sß-thalassemia, SD, SOArab)\n* Have one or more ulcers of the one or both leg or foot\n* Total surface area of leg ulcer(s) that will receive treatment must be no larger than 100 cm2\n* No history of congenital methemoglobinemia\n* Have documented normal Glucose-6-Phosphate Dehydrogenase (G6PD) activity\n\nExclusion Criteria:\n\n* Exposure to therapeutic nitric oxide, L-arginine, nitroprusside or nitroglycerine within the past 1 week\n* Subjects presenting with clinically diagnosed bacterial infection (e.g., osteomyelitis, pneumonia, sepsis or meningitis)\n* Subjects who have a pre-existing methemoglobinemia (more than 3.5% on two different occasions)\n* Patients who are currently enrolled in any other investigational drug study (this does not include observational or natural history protocols)\n* Use of Phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, 4 days prior to screening\n* Pregnant women - urine or serum Human chorionic gonadotropin (hCG)+ or nursing mothers\n* The following list of drugs and agents may cause methemoglobinemia and should be avoided while on this study:\n\nAnesthetics (local): Benzocaine, procaine, prilocaine, Anbesol, Orajel Antimalarials: chloroquine, primaquine, quinacrine Aniline dyes Chlorates Dapsone Diarylsulfonylureas Doxorubicin Metoclopramide Nitric and nitrous oxide Nitrobenzenes (shoe and floor polish and in paint solvents) Nitroethane (artificial nail remover, propellant, fuel additive) Nitrofurantoin (furadantin) Pyridium (phenazopyridine) Phenacetin Phenylhydrazine Rasburicase Sulfonamides (sulfacetamide, sulfamethoxazole, sulfanilamide, sulfapyridine)'}, 'identificationModule': {'nctId': 'NCT02863068', 'briefTitle': 'Topical Sodium Nitrite in Sickle Cell Disease and Leg Ulcers', 'organization': {'class': 'OTHER', 'fullName': 'Montefiore Medical Center'}, 'officialTitle': 'A Phase II Study of Topical Sodium Nitrite in Patients With Sickle Cell and Leg Ulcers', 'orgStudyIdInfo': {'id': '2016-6015'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'control', 'description': 'patients will receive placebo and standard of care', 'interventionNames': ['Other: Placebo']}, {'type': 'EXPERIMENTAL', 'label': 'topical sodium nitrite', 'description': 'patients will receive 2% topical sodium nitrite cream and standard of care', 'interventionNames': ['Drug: Topical Sodium Nitrite']}], 'interventions': [{'name': 'Topical Sodium Nitrite', 'type': 'DRUG', 'description': 'Subjects will have 0.1 cm of 2% sodium nitrite cream applied per 1 cm2 of the total ulcerated area. Areas will be rounded to the nearest 1 cm2. If a subject has more than one ulcer, all of them will be treated with either "study cream" in this intervention.', 'armGroupLabels': ['topical sodium nitrite']}, {'name': 'Placebo', 'type': 'OTHER', 'description': 'Subjects will have Placebo applied to total ulcerated area. If a subject has more than one ulcer, all of them will be treated with placebo in this intervention.', 'armGroupLabels': ['control']}]}, 'contactsLocationsModule': {'locations': [{'zip': '10461', 'city': 'The Bronx', 'state': 'New York', 'country': 'United States', 'facility': 'Montefiore Medical Center - Albert Einstein College of Medicine', 'geoPoint': {'lat': 40.84985, 'lon': -73.86641}}, {'zip': '27710', 'city': 'Durham', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Duke University Medical Center', 'geoPoint': {'lat': 35.99403, 'lon': -78.89862}}, {'zip': '15260', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pittsburgh', 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}], 'overallOfficials': [{'name': 'Caterina Minniti, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Montefiore Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'caterina P minniti', 'class': 'OTHER'}, 'collaborators': [{'name': 'Duke University', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'caterina P minniti', 'investigatorAffiliation': 'Montefiore Medical Center'}}}}