Ignite Creation Date:
2025-12-25 @ 12:27 AM
Ignite Modification Date:
2025-12-25 @ 10:33 PM
Study NCT ID:
NCT00200967
Status:
COMPLETED
Last Update Posted:
2018-01-23
First Post:
2005-09-12
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001249', 'term': 'Asthma'}], 'ancestors': [{'id': 'D001982', 'term': 'Bronchial Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D008173', 'term': 'Lung Diseases, Obstructive'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012130', 'term': 'Respiratory Hypersensitivity'}, {'id': 'D006969', 'term': 'Hypersensitivity, Immediate'}, {'id': 'D006967', 'term': 'Hypersensitivity'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068299', 'term': 'Salmeterol Xinafoate'}, {'id': 'D001507', 'term': 'Beclomethasone'}], 'ancestors': [{'id': 'D000420', 'term': 'Albuterol'}, {'id': 'D004983', 'term': 'Ethanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D010627', 'term': 'Phenethylamines'}, {'id': 'D005021', 'term': 'Ethylamines'}, {'id': 'D011246', 'term': 'Pregnadienetriols'}, {'id': 'D011245', 'term': 'Pregnadienes'}, {'id': 'D011278', 'term': 'Pregnanes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D013258', 'term': 'Steroids, Chlorinated'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'vchinchi@psu.edu', 'phone': '717-531-4262', 'title': 'Vernon M. Chinchilli', 'organization': 'Penn State College of Medicine'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'The study used a moderately high dose of ICS. Genotype-specific effects may be evident at lower doses of ICS often used in combination therapy. Also, short-acting β2-agonists have been shown to have genotype-specific effects on asthma outcomes.'}}, 'adverseEventsModule': {'timeFrame': '1 year', 'description': 'does not differ from clinicaltrials.gov definitions', 'eventGroups': [{'id': 'EG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA', 'otherNumAtRisk': 42, 'otherNumAffected': 20, 'seriousNumAtRisk': 42, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA', 'otherNumAtRisk': 45, 'otherNumAffected': 20, 'seriousNumAtRisk': 45, 'seriousNumAffected': 4}], 'otherEvents': [{'term': 'respiratory infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 42, 'numEvents': 100, 'numAffected': 20}, {'groupId': 'EG001', 'numAtRisk': 45, 'numEvents': 98, 'numAffected': 20}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'hospitalization', 'stats': [{'groupId': 'EG000', 'numAtRisk': 42, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 45, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'hospitalization', 'stats': [{'groupId': 'EG000', 'numAtRisk': 42, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 45, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Psychiatric disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Morning (AM) Peak Expiratory Flow (PEF) Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '-21', 'groupId': 'OG000', 'lowerLimit': '-31', 'upperLimit': '-12'}, {'value': '-22', 'groupId': 'OG001', 'lowerLimit': '-32', 'upperLimit': '-11'}]}]}], 'analyses': [{'pValue': '0.99', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0', 'ciLowerLimit': '-14', 'ciUpperLimit': '14', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '7', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for AM PEF rate.', 'groupDescription': 'A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design. A sample size of 40 participants per genotype was required to detect a difference of 25 L/min in AM PEF (and relevant effect sizes for secondary outcomes) with a two-sided, 0.05 significance level test with 90% statistical power and a 15% drop-out rate.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for AM PEF rate', 'unitOfMeasure': 'liters per minute', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An intention-to-treat (ITT) paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Evening (PM) Peak Expiratory Flow (PEF) Rate', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '-25', 'groupId': 'OG000', 'lowerLimit': '-34', 'upperLimit': '-16'}, {'value': '-24', 'groupId': 'OG001', 'lowerLimit': '-34', 'upperLimit': '-14'}]}]}], 'analyses': [{'pValue': '0.82', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '-1', 'ciLowerLimit': '-15', 'ciUpperLimit': '12', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '7', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for PM PEF rate.', 'groupDescription': 'A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for PM PEF rate', 'unitOfMeasure': 'liters per minute', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Peak Expiratory Flow (PEF) Variability', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '0.2', 'groupId': 'OG000', 'lowerLimit': '-0.6', 'upperLimit': '1.0'}, {'value': '0.7', 'groupId': 'OG001', 'lowerLimit': '0.0', 'upperLimit': '1.4'}]}]}], 'analyses': [{'pValue': '0.31', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '-0.6', 'ciLowerLimit': '-1.6', 'ciUpperLimit': '0.5', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.5', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for PEF variability.', 'groupDescription': 'A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for PEF variability, where PEF variability is defined as 100% x (PM PEF - AM PEF)/(PM PEF)', 'unitOfMeasure': 'percentage', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Asthma Symptoms', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '0.04', 'groupId': 'OG000', 'lowerLimit': '0.00', 'upperLimit': '0.12'}, {'value': '0.00', 'groupId': 'OG001', 'lowerLimit': '-0.01', 'upperLimit': '0.02'}]}]}], 'analyses': [{'pValue': '0.09', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.02', 'ciLowerLimit': '-0.02', 'ciUpperLimit': '0.07', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.02', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for asthma symptoms.', 'groupDescription': 'A mixed-effects linear model was attempted but could not converge because very few symptoms were recorded, so a nonparametric analysis was applied.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for asthma symptoms (0=absent, 1=mild, 2=moderate, 3=severe).', 'unitOfMeasure': 'units on a scale', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Rescue Medication (Ipratropium and Albuterol) Use', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '0.2', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '0.5'}, {'value': '0.0', 'groupId': 'OG001', 'lowerLimit': '0.0', 'upperLimit': '0.2'}]}]}], 'analyses': [{'pValue': '0.25', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.0', 'ciLowerLimit': '-0.1', 'ciUpperLimit': '0.2', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.1', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for rescue medication use.', 'groupDescription': 'A mixed-effects linear model was attempted but could not converge because very few usages of rescue medications were recorded, so a nonparametric analysis was applied.', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'MEAN', 'timeFrame': 'Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for rescue medication use', 'unitOfMeasure': 'puffs per day', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Spirometry Forced Expiratory Volume in One Second (FEV1), Pre-bronchodilator', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.08', 'groupId': 'OG000', 'lowerLimit': '-0.13', 'upperLimit': '-0.03'}, {'value': '-0.04', 'groupId': 'OG001', 'lowerLimit': '-0.09', 'upperLimit': '0.00'}]}]}], 'analyses': [{'pValue': '0.34', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '-0.03', 'ciLowerLimit': '-0.10', 'ciUpperLimit': '0.03', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator.', 'groupDescription': 'A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator', 'unitOfMeasure': 'liters', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.04', 'groupId': 'OG000', 'lowerLimit': '-0.08', 'upperLimit': '0.01'}, {'value': '-0.03', 'groupId': 'OG001', 'lowerLimit': '-0.09', 'upperLimit': '0.03'}]}]}], 'analyses': [{'pValue': '0.91', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.00', 'ciLowerLimit': '-0.08', 'ciUpperLimit': '0.07', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.03', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for Spirometry FVC, pre-bronchodilator.', 'groupDescription': 'A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for Spirometry FVC, pre-bronchodilator', 'unitOfMeasure': 'liters', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Spirometry Peak Expiratory Flow (PEF) Rate, Pre-bronchodilator', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '-17', 'groupId': 'OG000', 'lowerLimit': '-27', 'upperLimit': '-8'}, {'value': '-17', 'groupId': 'OG001', 'lowerLimit': '-27', 'upperLimit': '-6'}]}]}], 'analyses': [{'pValue': '0.93', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '-1', 'ciLowerLimit': '-15', 'ciUpperLimit': '14', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '7', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator.', 'groupDescription': 'A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator', 'unitOfMeasure': 'liters per minute', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Exhaled Nitric Oxide (eNO)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '0.12', 'groupId': 'OG000', 'lowerLimit': '-0.01', 'upperLimit': '0.24'}, {'value': '-0.02', 'groupId': 'OG001', 'lowerLimit': '-0.15', 'upperLimit': '0.11'}]}]}], 'analyses': [{'pValue': '0.13', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.14', 'ciLowerLimit': '-0.04', 'ciUpperLimit': '0.31', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.08', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for eNO.', 'groupDescription': 'A mixed-effects linear model was applied to the natural logarithm of eNO to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for eNO', 'unitOfMeasure': 'parts per billion', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Exhaled Breath Condensate (EBC)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.10', 'groupId': 'OG000', 'lowerLimit': '-0.45', 'upperLimit': '0.26'}, {'value': '-0.03', 'groupId': 'OG001', 'lowerLimit': '-0.37', 'upperLimit': '0.31'}]}]}], 'analyses': [{'pValue': '0.79', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '-0.07', 'ciLowerLimit': '-0.56', 'ciUpperLimit': '0.43', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.24', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for EBC.', 'groupDescription': 'A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Clinic visits at weeks 0, 10, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for EBC', 'unitOfMeasure': 'pH', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Methacholine Provocative Concentration 20 (PC20)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '0.06', 'groupId': 'OG000', 'lowerLimit': '-0.60', 'upperLimit': '0.71'}, {'value': '-1.27', 'groupId': 'OG001', 'lowerLimit': '-1.87', 'upperLimit': '-0.66'}]}]}], 'analyses': [{'pValue': '0.004', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '1.32', 'ciLowerLimit': '0.43', 'ciUpperLimit': '2.21', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.45', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for methacholine PC20.', 'groupDescription': 'A mixed-effects linear model was applied to the base-2 logarithm of the methacholine PC20 to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'Clinic visits at weeks 0 and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for methacholine PC20', 'unitOfMeasure': 'milligrams per milliliter', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}, {'type': 'SECONDARY', 'title': 'Asthma Control Questionnaire (ACQ)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'OG000'}, {'value': '45', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'OG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'classes': [{'categories': [{'measurements': [{'value': '0.13', 'groupId': 'OG000', 'lowerLimit': '-0.06', 'upperLimit': '0.32'}, {'value': '0.11', 'groupId': 'OG001', 'lowerLimit': '-0.04', 'upperLimit': '0.26'}]}]}], 'analyses': [{'pValue': '0.89', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Mean Difference (Final Values)', 'ciPctValue': '95', 'paramValue': '0.02', 'ciLowerLimit': '-0.23', 'ciUpperLimit': '0.26', 'dispersionType': 'STANDARD_ERROR_OF_MEAN', 'dispersionValue': '0.12', 'estimateComment': 'The comparison represents the difference between Arg/Arg and Gly/Gly participants based on the change between placebo salmeterol and active salmeterol for ACQ.', 'groupDescription': 'A mixed-effects linear model was applied to account for the repeated measurements within each treatment period of the crossover design.', 'statisticalMethod': 'Mixed Models Analysis', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Clinic visits at weeks 0 and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for ACQ, where ACQ ranges from 0 (best asthma control) to 6 (worst asthma control).', 'unitOfMeasure': 'units on a scale', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'An ITT paradigm was invoked in which the available data (without any imputation for missing data) on all randomized participants were included.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'FG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}], 'periods': [{'title': 'First Treatment Period', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '42'}, {'groupId': 'FG001', 'numSubjects': '45'}]}, {'type': 'First Treatment Period', 'achievements': [{'groupId': 'FG000', 'numSubjects': '42'}, {'groupId': 'FG001', 'numSubjects': '45'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '36'}, {'groupId': 'FG001', 'numSubjects': '44'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Pregnancy', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}, {'title': 'Wash-out Period', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '36'}, {'groupId': 'FG001', 'numSubjects': '44'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '36'}, {'groupId': 'FG001', 'numSubjects': '43'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}, {'title': 'Second Treatment Period', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '36'}, {'groupId': 'FG001', 'numSubjects': '43'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '35'}, {'groupId': 'FG001', 'numSubjects': '41'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '2'}]}]}, {'title': 'Run-out Period', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '35'}, {'groupId': 'FG001', 'numSubjects': '41'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '34'}, {'groupId': 'FG001', 'numSubjects': '41'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Recruitment for the LARGE trial began in November 2004 and the final participant visits occurred in February 2008. Seven academic medical centers throughout the US recruited the participants.', 'preAssignmentDetails': '474 participants were screened: 78 had B16 Arg/Arg genotype; 166 had B16 Gly/Gly genotype; 230 had Arg/Gly genotype. 47 matched Arg/Arg-Gly/Gly pairs entered the 8-week run-in period. 42 Arg/Arg were randomized (2 withdrew, 2 noncompliant, 1 lost); 45 Gly/Gly were randomized (1 withdrew, 1 noncompliant).'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '42', 'groupId': 'BG000'}, {'value': '45', 'groupId': 'BG001'}, {'value': '87', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'id': 'BG001', 'title': 'B16 Gly/Gly', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA'}, {'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': '42', 'groupId': 'BG000'}, {'value': '45', 'groupId': 'BG001'}, {'value': '87', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '39', 'spread': '11', 'groupId': 'BG000'}, {'value': '42', 'spread': '12', 'groupId': 'BG001'}, {'value': '41', 'spread': '12', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '32', 'groupId': 'BG000'}, {'value': '29', 'groupId': 'BG001'}, {'value': '61', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '16', 'groupId': 'BG001'}, {'value': '26', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '42', 'groupId': 'BG000'}, {'value': '45', 'groupId': 'BG001'}, {'value': '87.0', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 87}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2004-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-12', 'completionDateStruct': {'date': '2008-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-12-26', 'studyFirstSubmitDate': '2005-09-12', 'resultsFirstSubmitDate': '2009-03-05', 'studyFirstSubmitQcDate': '2005-09-12', 'lastUpdatePostDateStruct': {'date': '2018-01-23', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2009-04-08', 'studyFirstPostDateStruct': {'date': '2005-09-20', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2009-06-02', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2008-02', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Morning (AM) Peak Expiratory Flow (PEF) Rate', 'timeFrame': 'Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for AM PEF rate'}], 'secondaryOutcomes': [{'measure': 'Evening (PM) Peak Expiratory Flow (PEF) Rate', 'timeFrame': 'Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for PM PEF rate'}, {'measure': 'Peak Expiratory Flow (PEF) Variability', 'timeFrame': 'Measured daily using a hand-held peak flow meter, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for PEF variability, where PEF variability is defined as 100% x (PM PEF - AM PEF)/(PM PEF)'}, {'measure': 'Asthma Symptoms', 'timeFrame': 'Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for asthma symptoms (0=absent, 1=mild, 2=moderate, 3=severe).'}, {'measure': 'Rescue Medication (Ipratropium and Albuterol) Use', 'timeFrame': 'Recorded daily on a diary card, and then averaged between weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for rescue medication use'}, {'measure': 'Spirometry Forced Expiratory Volume in One Second (FEV1), Pre-bronchodilator', 'timeFrame': 'Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for Spirometry FEV1, pre-bronchodilator'}, {'measure': 'Spirometry Forced Vital Capacity (FVC), Pre-bronchodilator', 'timeFrame': 'Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for Spirometry FVC, pre-bronchodilator'}, {'measure': 'Spirometry Peak Expiratory Flow (PEF) Rate, Pre-bronchodilator', 'timeFrame': 'Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for Spirometry PEF rate, pre-bronchodilator'}, {'measure': 'Exhaled Nitric Oxide (eNO)', 'timeFrame': 'Clinic visits at weeks 0, 2, 6, 10, 14, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for eNO'}, {'measure': 'Exhaled Breath Condensate (EBC)', 'timeFrame': 'Clinic visits at weeks 0, 10, and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for EBC'}, {'measure': 'Methacholine Provocative Concentration 20 (PC20)', 'timeFrame': 'Clinic visits at weeks 0 and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for methacholine PC20'}, {'measure': 'Asthma Control Questionnaire (ACQ)', 'timeFrame': 'Clinic visits at weeks 0 and 18 of each treatment period', 'description': 'Change between placebo salmeterol and active salmeterol for ACQ, where ACQ ranges from 0 (best asthma control) to 6 (worst asthma control).'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Asthma']}, 'referencesModule': {'references': [{'pmid': '19932356', 'type': 'RESULT', 'citation': "Wechsler ME, Kunselman SJ, Chinchilli VM, Bleecker E, Boushey HA, Calhoun WJ, Ameredes BT, Castro M, Craig TJ, Denlinger L, Fahy JV, Jarjour N, Kazani S, Kim S, Kraft M, Lazarus SC, Lemanske RF Jr, Markezich A, Martin RJ, Permaul P, Peters SP, Ramsdell J, Sorkness CA, Sutherland ER, Szefler SJ, Walter MJ, Wasserman SI, Israel E; National Heart, Lung and Blood Institute's Asthma Clinical Research Network. Effect of beta2-adrenergic receptor polymorphism on response to longacting beta2 agonist in asthma (LARGE trial): a genotype-stratified, randomised, placebo-controlled, crossover trial. Lancet. 2009 Nov 21;374(9703):1754-64. doi: 10.1016/S0140-6736(09)61492-6."}], 'seeAlsoLinks': [{'url': 'http://www.acrn.org', 'label': 'Asthma Clinical Research Network (ACRN) Website'}]}, 'descriptionModule': {'briefSummary': 'The purpose of this trial is to determine whether regularly scheduled use of an inhaled long-acting beta agonist (salmeterol) in the setting of concomitant use of inhaled corticosteroids (beclomethasone hydroflouroalkane (HFA) inhaler) will have a detrimental effect on asthma control in people who bear the B16-Arg/Arg genotype of the beta-2 adrenergic receptor gene, as compared to people with asthma of similar severity who bear the B16-Gly/Gly genotype.', 'detailedDescription': 'BACKGROUND:\n\nThe purpose of this study is to compare the effects of a long-acting beta agonist in patients with asthma receiving inhaled corticosteroids who express two distinct polymorphisms of the beta-2 adrenergic receptor.\n\nDESIGN NARRATIVE:\n\nParticipants were homozygous for arginine or glycine at the 16th amino-acid position of the β-2 adrenergic receptor (B16 Arg/Arg or B16 Gly/Gly). Individuals were matched against their opposite genotype by forced expiratory volume in one second (FEV1) and race. Matched participants entered an 8-week run-in period. This is a 62-week crossover design where subjects receive the following therapies:\n\n* Beclomethasone HFA (240 µg twice a day (BID)) + as-needed (PRN) albuterol: 8-week run-in\n* Beclomethasone HFA (240 µg BID) + salmeterol (50 µg BID) + PRN ipratropium bromide + PRN albuterol: 18-week treatment period\n* Beclomethasone HFA (240 µg BID) + PRN albuterol: 8-week run-out\n* Beclomethasone HFA (240 µg BID) + placebo salmeterol + PRN ipratropium bromide + PRN albuterol: 18-week treatment period\n* Beclomethasone HFA (240 µg BID) + PRN albuterol: 10-week run-out\n\nThe order of treatments received during the two treatment periods is randomized.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '90 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female, ages 18 and older\n* Clinical history consistent with asthma\n* For subjects regularly using inhaled corticosteroids, FEV1 50% of predicted, methacholine PC20 FEV1 16 mg/ml or 12% and 200 ml, improvement in FEV1 after 2 puffs of inhaled albuterol\n* For subjects not regularly using inhaled corticosteroids, FEV1 40% of predicted, methacholine PC20 FEV1 8 mg/ml or 12% and 200 ml, improvement in FEV1 after 2 puffs of inhaled albuterol\n* Genotype eligibility (determined during screening)\n\nExclusion Criteria:\n\n* Smoker (total smoking history must be less than 10 pack years)\n* Significant unstable medical condition other than asthma\n* History of life-threatening asthma requiring treatment with intubation and mechanical ventilation in the past 10 years\n* Pregnant or lactating'}, 'identificationModule': {'nctId': 'NCT00200967', 'briefTitle': 'Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)', 'organization': {'class': 'OTHER', 'fullName': 'Milton S. Hershey Medical Center'}, 'officialTitle': 'Asthma Clinical Research Network (ACRN) Trial - Long-Acting Beta Agonist Response by Genotype (LARGE)', 'orgStudyIdInfo': {'id': '262'}, 'secondaryIdInfos': [{'id': '5U10HL074231', 'link': 'https://reporter.nih.gov/quickSearch/5U10HL074231', 'type': 'NIH'}, {'id': 'U10HL074073', 'link': 'https://reporter.nih.gov/quickSearch/U10HL074073', 'type': 'NIH'}, {'id': 'U10HL074204', 'link': 'https://reporter.nih.gov/quickSearch/U10HL074204', 'type': 'NIH'}, {'id': 'U10HL074208', 'link': 'https://reporter.nih.gov/quickSearch/U10HL074208', 'type': 'NIH'}, {'id': 'U10HL074212', 'link': 'https://reporter.nih.gov/quickSearch/U10HL074212', 'type': 'NIH'}, {'id': 'U10HL074218', 'link': 'https://reporter.nih.gov/quickSearch/U10HL074218', 'type': 'NIH'}, {'id': 'U10HL074225', 'link': 'https://reporter.nih.gov/quickSearch/U10HL074225', 'type': 'NIH'}, {'id': 'U10HL074227', 'link': 'https://reporter.nih.gov/quickSearch/U10HL074227', 'type': 'NIH'}, {'id': 'U10HL074231', 'link': 'https://reporter.nih.gov/quickSearch/U10HL074231', 'type': 'NIH'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'B16 Arg/Arg', 'description': 'B16 Arg/Arg genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone hydroflouroalkane (HFA), followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA', 'interventionNames': ['Drug: salmeterol', 'Drug: beclomethasone HFA']}, {'type': 'EXPERIMENTAL', 'label': 'B16 Gly/Gly', 'description': 'B16 Gly/Gly genotype Sequence 1: inhaled salmeterol + inhaled beclomethasone HFA, followed by inhaled placebo salmeterol + inhaled beclomethasone HFA Sequence 2: inhaled placebo salmeterol + inhaled beclomethasone HFA, followed by inhaled salmeterol + inhaled beclomethasone HFA', 'interventionNames': ['Drug: salmeterol', 'Drug: beclomethasone HFA']}], 'interventions': [{'name': 'salmeterol', 'type': 'DRUG', 'otherNames': ['Serevent'], 'description': '50 micrograms (mcg) twice per day (BID) (Serevent 50 mcg diskus, GlaxoSmithKline (GSK), North Carolina)', 'armGroupLabels': ['B16 Arg/Arg', 'B16 Gly/Gly']}, {'name': 'beclomethasone HFA', 'type': 'DRUG', 'otherNames': ['QVAR'], 'description': '240 mcg beclomethasone HFA (QVAR, Teva Pharmaceutical Industries)', 'armGroupLabels': ['B16 Arg/Arg', 'B16 Gly/Gly']}]}, 'contactsLocationsModule': {'locations': [{'zip': '92103', 'city': 'San Diego', 'state': 'California', 'country': 'United States', 'facility': 'University of California, San Diego', 'geoPoint': {'lat': 32.71571, 'lon': -117.16472}}, {'zip': '94143-0130', 'city': 'San Francisco', 'state': 'California', 'country': 'United States', 'facility': 'University of California, San Francisco', 'geoPoint': {'lat': 37.77493, 'lon': -122.41942}}, {'zip': '80206', 'city': 'Denver', 'state': 'Colorado', 'country': 'United States', 'facility': 'National Jewish Medical & Research Center', 'geoPoint': {'lat': 39.73915, 'lon': -104.9847}}, {'zip': '02115', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': "Brigham & Women's Hospital", 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}, {'zip': '27103', 'city': 'Winston-Salem', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Wake Forest University Health Sciences', 'geoPoint': {'lat': 36.09986, 'lon': -80.24422}}, {'zip': '53792-3244', 'city': 'Madison', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'University of Wisconsin Madison', 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}], 'overallOfficials': [{'name': 'Homer Boushey', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, San Francisco'}, {'name': 'Mario Castro', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Washington University School of Medicine'}, {'name': 'Vernon M. Chinchilli, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Milton S. Hershey Medical Center'}, {'name': 'Elliot Israel', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Brigham and Women's Hospital"}, {'name': 'Robert Lemanske', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Wisconsin, Madison'}, {'name': 'Richard Martin', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'National Jewish Medical & Research Center'}, {'name': 'Stephen Peters', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Wake Forest University Health Sciences'}, {'name': 'Stephen Wasserman', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, San Diego'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Milton S. Hershey Medical Center', 'class': 'OTHER'}, 'collaborators': [{'name': 'National Heart, Lung, and Blood Institute (NHLBI)', 'class': 'NIH'}, {'name': 'Asthma Clinical Research Network', 'class': 'NETWORK'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor and Chair, Department of Public Health Sciences', 'investigatorFullName': 'Vernon M. Chinchilli, PhD', 'investigatorAffiliation': 'Milton S. Hershey Medical Center'}}}}