Ignite Creation Date:
2025-12-25 @ 4:26 AM
Ignite Modification Date:
2025-12-26 @ 3:30 AM
Study NCT ID:
NCT01060020
Status:
COMPLETED
Last Update Posted:
2018-04-25
First Post:
2010-01-28
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D001024', 'term': 'Aortic Valve Stenosis'}, {'id': 'D006976', 'term': 'Hypertension, Pulmonary'}], 'ancestors': [{'id': 'D000082862', 'term': 'Aortic Valve Disease'}, {'id': 'D006349', 'term': 'Heart Valve Diseases'}, {'id': 'D006331', 'term': 'Heart Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D014694', 'term': 'Ventricular Outflow Obstruction'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D006973', 'term': 'Hypertension'}, {'id': 'D014652', 'term': 'Vascular Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000068677', 'term': 'Sildenafil Citrate'}], 'ancestors': [{'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D010879', 'term': 'Piperazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'brlindman@wustl.edu', 'phone': '314-747-3617', 'title': 'Brian R. Lindman, MD, Assistant Professor of Medicine', 'organization': 'Washington University School of Medicine'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab.\n\nSildenafil: Single oral dose of 40mg or 80mg of Sildenafil', 'otherNumAtRisk': 20, 'otherNumAffected': 1, 'seriousNumAtRisk': 20, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'hypertensive emergency', 'stats': [{'groupId': 'EG000', 'numAtRisk': 20, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Hypotension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 20, 'numAffected': 2}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'SVT', 'stats': [{'groupId': 'EG000', 'numAtRisk': 20, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab.\n\nSildenafil: Single oral dose of 40mg or 80mg of Sildenafil'}], 'classes': [{'categories': [{'measurements': [{'value': '-25', 'groupId': 'OG000', 'lowerLimit': '-32', 'upperLimit': '-21'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline and 60 minutes after drug administered', 'unitOfMeasure': 'percent change', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percent Change in Pulmonary Vascular Resistance in the Whole Cohort.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab. Each dose will be equally distributed among those with preserved (≥50%) and reduced (\\<50%) EF.\n\nSildenafil: Single oral dose of 40mg or 80mg of Sildenafil'}], 'classes': [{'categories': [{'measurements': [{'value': '-29', 'groupId': 'OG000', 'lowerLimit': '-49', 'upperLimit': '-13'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline and 60 minutes after drug administered', 'unitOfMeasure': 'percent change', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Percent Change in Cardiac Index.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab. Each dose will be equally distributed among those with preserved (≥50%) and reduced (\\<50%) EF.\n\nSildenafil: Single oral dose of 40mg or 80mg of Sildenafil'}], 'classes': [{'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000', 'lowerLimit': '-4', 'upperLimit': '12'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline and 60 minutes after drug administered', 'description': 'Cardiac index is cardiac output divided by body surface area.', 'unitOfMeasure': 'percent change', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Load Independent Index of Diastolic Filling.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab. Each dose will be equally distributed among those with preserved (≥50%) and reduced (\\<50%) EF.\n\nSildenafil: Single oral dose of 40mg or 80mg of Sildenafil'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '1.02', 'spread': '0.07', 'groupId': 'OG000'}]}]}, {'title': '60 minutes', 'categories': [{'measurements': [{'value': '1.03', 'spread': '0.08', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 60 minutes after drug administered', 'description': 'Measurements of the load independent index of diastolic filling were made with the parameterized diastolic filling formalism as previously described and validated with the use of transmitral Doppler E waves recorded during different respiratory states (regular breathing and held expiration and inspiration).', 'unitOfMeasure': 'unitless', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Global Longitudinal Strain', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab. Each dose will be equally distributed among those with preserved (≥50%) and reduced (\\<50%) EF.\n\nSildenafil: Single oral dose of 40mg or 80mg of Sildenafil'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '-13.5', 'spread': '4.3', 'groupId': 'OG000'}]}]}, {'title': '60 minutes', 'categories': [{'measurements': [{'value': '-13.8', 'spread': '3.9', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline and 60 minutes after drug administered', 'description': 'Global longitudinal strain was measured at baseline and 60 minutes after drug administration.', 'unitOfMeasure': 'percent', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab.\n\nSildenafil: Single oral dose of 40mg or 80mg of Sildenafil'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '20'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '20'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}], 'preAssignmentDetails': 'Participants stratified according to ejection fraction and randomized to either Sildenafil 40mg and 80mg Groups were combined into a single Arm/Group for analysis as pre-specified in the study protocol.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab.\n\nSildenafil: Single oral dose of 40mg or 80mg of Sildenafil'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '86', 'spread': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Black or African American', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '19', 'groupId': 'BG000'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-04', 'completionDateStruct': {'date': '2011-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-04-16', 'studyFirstSubmitDate': '2010-01-28', 'resultsFirstSubmitDate': '2018-01-25', 'studyFirstSubmitQcDate': '2010-01-28', 'lastUpdatePostDateStruct': {'date': '2018-04-25', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-04-16', 'studyFirstPostDateStruct': {'date': '2010-02-01', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-04-25', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2011-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort.', 'timeFrame': 'Baseline and 60 minutes after drug administered'}], 'secondaryOutcomes': [{'measure': 'Percent Change in Pulmonary Vascular Resistance in the Whole Cohort.', 'timeFrame': 'Baseline and 60 minutes after drug administered'}, {'measure': 'Percent Change in Cardiac Index.', 'timeFrame': 'Baseline and 60 minutes after drug administered', 'description': 'Cardiac index is cardiac output divided by body surface area.'}, {'measure': 'Load Independent Index of Diastolic Filling.', 'timeFrame': 'Baseline and 60 minutes after drug administered', 'description': 'Measurements of the load independent index of diastolic filling were made with the parameterized diastolic filling formalism as previously described and validated with the use of transmitral Doppler E waves recorded during different respiratory states (regular breathing and held expiration and inspiration).'}, {'measure': 'Global Longitudinal Strain', 'timeFrame': 'Baseline and 60 minutes after drug administered', 'description': 'Global longitudinal strain was measured at baseline and 60 minutes after drug administration.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Aortic valve stenosis', 'Sildenafil', 'Phosphodiesterase inhibitors', 'Hypertension, Pulmonary'], 'conditions': ['Aortic Stenosis']}, 'referencesModule': {'references': [{'pmid': '22447809', 'type': 'RESULT', 'citation': 'Lindman BR, Zajarias A, Madrazo JA, Shah J, Gage BF, Novak E, Johnson SN, Chakinala MM, Hohn TA, Saghir M, Mann DL. Effects of phosphodiesterase type 5 inhibition on systemic and pulmonary hemodynamics and ventricular function in patients with severe symptomatic aortic stenosis. Circulation. 2012 May 15;125(19):2353-62. doi: 10.1161/CIRCULATIONAHA.111.081125. Epub 2012 Mar 25.'}]}, 'descriptionModule': {'briefSummary': 'Pulmonary hypertension is common in patients with aortic stenosis and is associated with worse operative and long-term outcomes. Sildenafil has been shown to reduce pulmonary artery pressure and improve exercise performance in patients with left-sided heart failure, but this has not been tested in patients with aortic stenosis. We hypothesize that Sildenafil will produce a clinically significant decrease in pulmonary artery pressure in patients with severe aortic stenosis. The dose of Sildenafil that produces a significant decrease in pulmonary artery pressure will be safe and well tolerated in patients with and without a depressed ejection fraction.', 'detailedDescription': 'Patients with severe aortic stenosis referred for a clinically ordered right and left heart catheterization will be eligible. Twenty subjects will be enrolled: 10 patients will receive 40mg and 10 patients will receive 80mg; each dose will be equally distributed among those with preserved (≥50%) and reduced (\\<50%) EF. Subjects will get a baseline echo prior to the heart catheterization. Baseline invasive hemodynamic measurements will be performed using a Swan Ganz catheter. A single oral dose of sildenafil will then be administered (40mg or 80mg), followed by invasive hemodynamic measurements at 30 and 60 minutes. Also at 60 minutes, limited echocardiographic images will be obtained.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Severe aortic stenosis (AVA \\< 1.0 cm2)\n* Referred for a clinically ordered right and left heart catheterization\n* 18 years of age and older\n* Able and willing to comply with all requirements of the study\n\nExclusion Criteria:\n\n* Nitrate use within 24 hours\n* SBP \\< 110 mmHg or MAP \\< 75 mmHg\n* Severe mitral regurgitation\n* Severe aortic regurgitation\n* Increased risk of priapism\n* Retinal or optic nerve problems or unexplained visual disturbance\n* Alpha antagonists or cytochrome P450 3A4 inhibitors use within 24 hours\n* Current or recent (≤ 30 days) acute coronary syndrome\n* O2 sat \\< 90% on room air\n* Females that are pregnant or believe they may be pregnant\n* Any condition which the PI determines will place the subject at increased risk or is likely to yield unreliable hemodynamic data\n* Unwilling to provide informed consent'}, 'identificationModule': {'nctId': 'NCT01060020', 'briefTitle': 'Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis', 'organization': {'class': 'OTHER', 'fullName': 'Washington University School of Medicine'}, 'officialTitle': 'Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis', 'orgStudyIdInfo': {'id': '09-1780'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Sildenafil 40mg or 80mg', 'description': 'A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab. Each dose will be equally distributed among those with preserved (≥50%) and reduced (\\<50%) EF.', 'interventionNames': ['Drug: Sildenafil']}], 'interventions': [{'name': 'Sildenafil', 'type': 'DRUG', 'otherNames': ['Revatio', 'Viagra'], 'description': 'Single oral dose of 40mg or 80mg of Sildenafil', 'armGroupLabels': ['Sildenafil 40mg or 80mg']}]}, 'contactsLocationsModule': {'locations': [{'zip': '63110', 'city': 'St Louis', 'state': 'Missouri', 'country': 'United States', 'facility': 'Washington University School of Medicine', 'geoPoint': {'lat': 38.62727, 'lon': -90.19789}}], 'overallOfficials': [{'name': 'Brian R. Lindman, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Washington University School of Medicine'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Washington University School of Medicine', 'class': 'OTHER'}, 'collaborators': [{'name': 'Barnes-Jewish Hospital', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Assistant Professor of Medicine', 'investigatorFullName': 'Brian Lindman, MD', 'investigatorAffiliation': 'Washington University School of Medicine'}}}}