Ignite Creation Date:
2025-12-25 @ 3:46 AM
Ignite Modification Date:
2025-12-26 @ 2:33 AM
Study NCT ID:
NCT03500302
Status:
COMPLETED
Last Update Posted:
2020-07-24
First Post:
2017-11-27
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Effect of Evolocumab on Coronary Endothelial Function
Sponsor:
Organization:
Raw JSON
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The percent change from week 1 to week 6 is presented below.', 'unitOfMeasure': 'percent change in coronary artery area', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'LDL Cholesterol Level', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Evolocumab', 'description': 'Patients with HIV receiving Evolocumab sq (2 doses total)'}], 'classes': [{'categories': [{'measurements': [{'value': '37', 'spread': '19', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At 6 weeks', 'description': 'LDL cholesterol level: mg/dL.', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Evolocumab', 'description': 'All enrolled patients (people living with HIV) who received evolocumab sq once a month for a total of two doses'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Evolocumab Group', 'description': 'Patients (people living with HIV) who received Evolocumab sq once a month for total of 2 doses'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '19', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'calculatePct': False, 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '52', 'spread': '9', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '4', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '15', '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': '14', 'groupId': 'BG000'}]}, {'title': 'White', 'measurements': [{'value': '5', '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'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '19', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Body Mass Index (BMI)', 'classes': [{'categories': [{'measurements': [{'value': '26', 'spread': '5', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg/m^2', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2017-08-25', 'size': 221536, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_000.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2020-07-08T13:00', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Pilot clinical trial to study HIV+ patients with baseline coronary endothelial dysfunction and assess changes in that function from the baseline measure to 1 and 6 weeks following initiation of therapy with evolocumab so as to test the hypotheses that PCSK9 inhibition with evolocumab improves coronary endothelial function (CEF) measured directly and non-invasively with MRI at 1 week and 6 weeks after initiation of evolocumab.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 19}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2018-05-04', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-07', 'completionDateStruct': {'date': '2019-11-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-07-23', 'studyFirstSubmitDate': '2017-11-27', 'resultsFirstSubmitDate': '2020-07-08', 'studyFirstSubmitQcDate': '2018-04-12', 'lastUpdatePostDateStruct': {'date': '2020-07-24', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-07-23', 'studyFirstPostDateStruct': {'date': '2018-04-18', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2020-07-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2019-11-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Coronary Endothelial Function as Assessed by Percent Coronary Artery Area Change With Isometric Handgrip Exercise', 'timeFrame': '1 week and 6 weeks', 'description': 'Coronary endothelial function will be assessed by the percent change in cross sectional coronary artery area (measured on MRI) from rest to isometric handgrip stress exercise at week 1 and week 6. The percent change from week 1 to week 6 is presented below.'}], 'secondaryOutcomes': [{'measure': 'LDL Cholesterol Level', 'timeFrame': 'At 6 weeks', 'description': 'LDL cholesterol level: mg/dL.'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Human Immunodeficiency Virus', 'Coronary Artery Disease']}, 'referencesModule': {'references': [{'pmid': '32674634', 'type': 'DERIVED', 'citation': 'Leucker TM, Gerstenblith G, Schar M, Brown TT, Jones SR, Afework Y, Weiss RG, Hays AG. Evolocumab, a PCSK9-Monoclonal Antibody, Rapidly Reverses Coronary Artery Endothelial Dysfunction in People Living With HIV and People With Dyslipidemia. J Am Heart Assoc. 2020 Jul 21;9(14):e016263. doi: 10.1161/JAHA.120.016263. Epub 2020 Jul 17.'}]}, 'descriptionModule': {'briefSummary': 'The investigators propose a pilot study using (1) MRI to assess coronary artery endothelial function, (2) brachial ultrasound to assess systemic endothelial function, (3) serum markers of inflammation and of endothelial cell function and (4) echocardiographic measures of left ventricular diastolic and systolic properties, before and following initiation of PCSK9 antibody in HIV positive subjects.', 'detailedDescription': 'To evaluate the effect of the PCSK9 inhibitor evolocumab on coronary and systemic endothelial function, systemic biomarkers of endothelial function and of inflammation, and echocardiographic measures of left ventricular diastolic and systolic properties in subjects who are HIV+. Potential participants will be asked to undergo a screening MRI exam. Those who have evidence of coronary endothelial dysfunction on the MRI exam will receive evolocumab 420 mg sq (the dose that is approved for treatment of hypercholesterolemia) following the screening exam and again at one month. Repeat MRI and ultrasound measures of coronary and systemic endothelial function, as well as serum markers of endothelial function and inflammation, and echocardiographic measures of diastolic and systolic left ventricular function will be obtained at one and six weeks following the first administration of evolocumab.\n\nThe investigators will test the hypotheses that PCSK9 inhibition improves endothelial function measured non-invasively on MRI and systemic markers of inflammation at one week (+/- 3 days) and six weeks after initiation of the PCSK9 antibody.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Participants of either gender who are \\>21 years of age (no upper age limit)\n* HIV (Human Immunodeficiency Virus) positive and taking stable Anti-Retroviral Therapy (ART), no change in regimen in last 3 months)\n* Undetectable HIV viral load (plasma HIV RNA concentration, RNA=Ribonucleic Adic)\n* Abnormal coronary endothelial function on MRI (Magnetic Resonance Imaging) at baseline (\\<5% change in coronary cross sectional area during isometric handgrip exercise as compared to resting value).\n* Lipids at screening visit: Fasting LDL-C \\>70 mg/dL (LDL-C=Low Density Lipoprotein Cholesterol); fasting TG\\<500 mg/dL (TG=Triglycerides)\n* Permission of treating physician\n\nExclusion Criteria:\n\n* Patients unable to understand the risks, benefits, and alternatives of participation and give meaningful consent.\n* Patients with contraindications to MRI such as implanted metallic objects (pre-existing cardiac pacemakers, cerebral clips),\n* History of a recent cardiovascular or cerebrovascular events or procedure (e.g. myocardial infarction, stroke, transient ischemic attack, angioplasty, Coronary artery bypass surgery) during the past 90 days.\n* Subjects with prior exposure to evolocumab or another PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitor.\n* Pregnant women or breastfeeding women. Women of childbearing potential (even if using oral contraceptive agents) or intention to breastfeed.\n* History of alcoholism or drug addiction according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV criteria within 12 months prior to screening. Use of any recreational drugs within 6 months prior to screening.\n* Renal impairment defined by estimated glomerular filtration rate \\<45 ml/min.\n* Moderate-severe hepatic disease (elevation in hepatic transaminases \\>3x upper limit of normal, ULN) or direct bilirubin \\>3.0 X ULN at screening.\n* Cluster of differentiation 4 (CD4)\\<200 cell/mm3\n* Congestive heart failure, New York Heart Association functional class III or greater, or left ventricular ejection fraction measured by imaging known to be \\<30%. (Imaging not required for study inclusion).\n* History of allergic or anaphylactic reaction to any therapeutic monoclonal antibody (IgG protein) or molecules made of components of monoclonal antibodies\n* Active phase hepatitis. Stable patients with hepatitis B or C infection \\>3 years before randomization are eligible.'}, 'identificationModule': {'nctId': 'NCT03500302', 'acronym': 'EVOLVE', 'briefTitle': 'Effect of Evolocumab on Coronary Endothelial Function', 'organization': {'class': 'OTHER', 'fullName': 'Johns Hopkins University'}, 'officialTitle': 'Effect of Evolocumab on Coronary Endothelial Function', 'orgStudyIdInfo': {'id': 'IRB00127952'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Evolocumab', 'description': 'All enrolled patients will receive evolocumab sq once a month for a total of two doses', 'interventionNames': ['Drug: Evolocumab']}], 'interventions': [{'name': 'Evolocumab', 'type': 'DRUG', 'otherNames': ['Repatha'], 'description': 'Evolocumab sq once a month for a total of two doses', 'armGroupLabels': ['Evolocumab']}]}, 'contactsLocationsModule': {'locations': [{'zip': '21205', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'Johns Hopkins University', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}], 'overallOfficials': [{'name': 'Allison Hays, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Johns Hopkins University'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Johns Hopkins University', 'class': 'OTHER'}, 'collaborators': [{'name': 'American Heart Association', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}