Ignite Creation Date:
2025-12-24 @ 4:19 PM
Ignite Modification Date:
2026-03-09 @ 4:49 AM
Study NCT ID:
NCT02547766
Status:
COMPLETED
Last Update Posted:
2020-02-17
First Post:
2015-09-09
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Interleukin-1 Receptor Antagonist for the Treatment of Heart Failure in Patients With Left Ventricular Assist Devices
Sponsor:
Organization:
Raw JSON
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That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.\n\nAnakinra: Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.', 'otherNumAtRisk': 10, 'deathsNumAtRisk': 10, 'otherNumAffected': 0, 'seriousNumAtRisk': 10, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Biologic Efficacy: Inflammation Marker - C-Reactive Protein', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Anakinra Arm', 'description': 'All patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.\n\nAnakinra: Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.'}], 'classes': [{'title': 'Prior to Anakinra', 'categories': [{'measurements': [{'value': '2.5', 'groupId': 'OG000', 'lowerLimit': '1.1', 'upperLimit': '3.0'}]}]}, {'title': 'After Anakinra', 'categories': [{'measurements': [{'value': '0.6', 'groupId': 'OG000', 'lowerLimit': '0.4', 'upperLimit': '1.8'}]}]}, {'title': 'At 6 months', 'categories': [{'measurements': [{'value': '0.6', 'groupId': 'OG000', 'lowerLimit': '0.5', 'upperLimit': '1.7'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '6 months post treatment', 'description': 'The primary endpoint was a reduction in inflammatory markers, specifically C-reactive protein (CRP).', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Patients'}, {'type': 'SECONDARY', 'title': 'Biologic Efficacy: Inflammation Marker - Neutrophil Count', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Anakinra Arm', 'description': 'All patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.\n\nAnakinra: Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.'}], 'classes': [{'title': 'Prior to Anakinra', 'categories': [{'measurements': [{'value': '6.4', 'groupId': 'OG000', 'lowerLimit': '5.7', 'upperLimit': '6.7'}]}]}, {'title': 'After Anakinra', 'categories': [{'measurements': [{'value': '5.0', 'groupId': 'OG000', 'lowerLimit': '2.8', 'upperLimit': '5.4'}]}]}, {'title': 'At 6 months', 'categories': [{'measurements': [{'value': '4.4', 'groupId': 'OG000', 'lowerLimit': '3.6', 'upperLimit': '5.3'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '6 months post treatment', 'description': 'Secondary endpoints included the measure of additional inflammatory markers, including neutrophil count.', 'unitOfMeasure': '10^3 cells/µL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Patients'}, {'type': 'SECONDARY', 'title': 'Clinical Efficacy: Ejection Fraction', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Anakinra Arm', 'description': 'All patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.\n\nAnakinra: Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.'}], 'classes': [{'title': 'Prior to Anakinra', 'categories': [{'measurements': [{'value': '15', 'groupId': 'OG000', 'lowerLimit': '15', 'upperLimit': '30'}]}]}, {'title': 'After Anakinra', 'categories': [{'measurements': [{'value': '15', 'groupId': 'OG000', 'lowerLimit': '15', 'upperLimit': '47'}]}]}, {'title': 'At 6 months', 'categories': [{'measurements': [{'value': '25', 'groupId': 'OG000', 'lowerLimit': '15', 'upperLimit': '50'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '6 months post treatment', 'description': 'Clinical efficacy was a secondary endpoint that was measured using ejection fraction (EF)', 'unitOfMeasure': 'percentage of blood leaving heart', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Patients'}, {'type': 'SECONDARY', 'title': 'Biologic Efficacy: Inflammation Marker - TNFalpha', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Anakinra Arm', 'description': 'All patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.\n\nAnakinra: Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.'}], 'classes': [{'title': 'Prior to Anakinra', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000', 'lowerLimit': '4', 'upperLimit': '6'}]}]}, {'title': 'After Anakinra', 'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000', 'lowerLimit': '4', 'upperLimit': '30'}]}]}, {'title': 'At 6 months', 'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000', 'lowerLimit': '4', 'upperLimit': '33'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '6 months post treatment', 'description': 'Secondary endpoints included the measure of additional inflammatory markers, including TNFalpha.', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Patients'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Anakinra Arm', 'description': 'All patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.\n\nAnakinra: Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Anakinra Arm', 'description': 'All patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.\n\nAnakinra: Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '50', 'spread': '11', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '2', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '8', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 10}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-02', 'completionDateStruct': {'date': '2016-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-02-03', 'studyFirstSubmitDate': '2015-09-09', 'resultsFirstSubmitDate': '2018-06-11', 'studyFirstSubmitQcDate': '2015-09-10', 'lastUpdatePostDateStruct': {'date': '2020-02-17', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2020-02-03', 'studyFirstPostDateStruct': {'date': '2015-09-11', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2020-02-17', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Biologic Efficacy: Inflammation Marker - C-Reactive Protein', 'timeFrame': '6 months post treatment', 'description': 'The primary endpoint was a reduction in inflammatory markers, specifically C-reactive protein (CRP).'}], 'secondaryOutcomes': [{'measure': 'Biologic Efficacy: Inflammation Marker - Neutrophil Count', 'timeFrame': '6 months post treatment', 'description': 'Secondary endpoints included the measure of additional inflammatory markers, including neutrophil count.'}, {'measure': 'Clinical Efficacy: Ejection Fraction', 'timeFrame': '6 months post treatment', 'description': 'Clinical efficacy was a secondary endpoint that was measured using ejection fraction (EF)'}, {'measure': 'Biologic Efficacy: Inflammation Marker - TNFalpha', 'timeFrame': '6 months post treatment', 'description': 'Secondary endpoints included the measure of additional inflammatory markers, including TNFalpha.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Ventricular Assist Device', 'Recovery of Function'], 'conditions': ['Heart Failure']}, 'referencesModule': {'references': [{'pmid': '17079761', 'type': 'BACKGROUND', 'citation': 'Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, Banner NR, Khaghani A, Yacoub MH. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006 Nov 2;355(18):1873-84. doi: 10.1056/NEJMoa053063.'}, {'pmid': '23453459', 'type': 'BACKGROUND', 'citation': 'Abbate A, Van Tassell BW, Biondi-Zoccai G, Kontos MC, Grizzard JD, Spillman DW, Oddi C, Roberts CS, Melchior RD, Mueller GH, Abouzaki NA, Rengel LR, Varma A, Gambill ML, Falcao RA, Voelkel NF, Dinarello CA, Vetrovec GW. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study]. Am J Cardiol. 2013 May 15;111(10):1394-400. doi: 10.1016/j.amjcard.2013.01.287. Epub 2013 Feb 27.'}, {'pmid': '20451681', 'type': 'BACKGROUND', 'citation': 'Abbate A, Kontos MC, Grizzard JD, Biondi-Zoccai GG, Van Tassell BW, Robati R, Roach LM, Arena RA, Roberts CS, Varma A, Gelwix CC, Salloum FN, Hastillo A, Dinarello CA, Vetrovec GW; VCU-ART Investigators. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol. 2010 May 15;105(10):1371-1377.e1. doi: 10.1016/j.amjcard.2009.12.059. Epub 2010 Apr 2.'}, {'pmid': '23500219', 'type': 'BACKGROUND', 'citation': 'Drakos SG, Wever-Pinzon O, Selzman CH, Gilbert EM, Alharethi R, Reid BB, Saidi A, Diakos NA, Stoker S, Davis ES, Movsesian M, Li DY, Stehlik J, Kfoury AG; UCAR (Utah Cardiac Recovery Program) Investigators. Magnitude and time course of changes induced by continuous-flow left ventricular assist device unloading in chronic heart failure: insights into cardiac recovery. J Am Coll Cardiol. 2013 May 14;61(19):1985-94. doi: 10.1016/j.jacc.2013.01.072. Epub 2013 Mar 14.'}, {'pmid': '21451407', 'type': 'BACKGROUND', 'citation': 'Drakos SG, Kfoury AG, Selzman CH, Verma DR, Nanas JN, Li DY, Stehlik J. Left ventricular assist device unloading effects on myocardial structure and function: current status of the field and call for action. Curr Opin Cardiol. 2011 May;26(3):245-55. doi: 10.1097/HCO.0b013e328345af13.'}, {'pmid': '22760582', 'type': 'BACKGROUND', 'citation': 'Guglin M, Miller L. Myocardial recovery with left ventricular assist devices. Curr Treat Options Cardiovasc Med. 2012 Aug;14(4):370-83. doi: 10.1007/s11936-012-0190-9.'}, {'pmid': '33470637', 'type': 'DERIVED', 'citation': 'Healy AH, Bowen M, McKellar SH, Koliopoulou A, Drakos SG, Selzman CH. Interleukin-1 Receptor Antagonism as Adjunct Therapy for Heart Failure Patients with Left Ventricular Assist Devices. ASAIO J. 2021 Aug 1;67(8):e145-e147. doi: 10.1097/MAT.0000000000001347.'}]}, 'descriptionModule': {'briefSummary': 'Heart failure remains a major cause of morbidity and mortality. Many patients with heart failure receive support from a left ventricular assist device (LVAD) at some point in the course of their disease. Some of these LVAD patients experience a durable recovery after ventricular unloading with an LVAD, which may be associated with inhibition of inflammatory cytokines. This small pilot study aims to determine the biologic and clinical efficacy of an interleukin-1 receptor antagonist (Anakinra) at inducing myocardial recovery in patients supported with left ventricular assist devices.', 'detailedDescription': 'More than 5 million Americans have heart failure, a number that is expected to increase 25% by the year 2030. Fifty percent of individuals diagnosed with heart failure die within 5 years of diagnosis. Of those patients who currently have heart failure, 5-10% have Stage D disease, requiring specialized interventions such as chronic inotropic support, mechanical circulatory support, or transplantation. Transplantation is considered curative for heart failure, but only about 2,200 heart transplants take place each year. Due to the imbalance between donors and possible recipients, a large number of patients remain who could benefit from transplantation that will never receive a heart. Many patients receive left ventricular assist devices (LVADs) to support their failing hearts, increasing their chances of survival while they wait to undergo transplantation.\n\nIt has been shown that up to 19% of patients show durable echocardiographic recovery (as measured by left ventricular ejection fraction \\>40%) after ventricular unloading with an LVAD. Recovery mediated by unloading with the LVAD causes several changes at the molecular level. However, the mechanisms underlying recovery at the cellular level, also known as reverse remodeling, are only recently being studied. Thus, the window of opportunity to develop adjuvant treatments to enhance recovery is just now opening.\n\nInterestingly, patients that experience durable echocardiographic recovery have higher circulating levels of anti-inflammatory cytokines. Inhibition of inflammatory cytokines, such as with the use of receptor antagonists for inflammation-associated cytokines like Anakinra, has also been shown to reduce adverse myocardial remodeling after ischemic events and to increase exercise activity in patients with systolic heart failure. This study proposes the exogenous administration of Anakinra to end-stage heart failure patients supported with LVADs in an effort to increase both the number of patients who experience recovery and the magnitude of recovery.\n\nWhile this is a small trial aimed primarily at demonstrating biologic efficacy of Anakinra, clinical efficacy in this study is also investigated. Encouraging results in this pilot study may prompt the creation of a randomized, controlled trial designed to demonstrate efficacy from a functional clinical standpoint.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* To qualify for inclusion, patients must meet the following criteria: age \\>18 years at date of LVAD implantation who require circulatory support with an LVAD for either a bridge-to-transplant or destination therapy indication.\n* They must also be judged by the implanting surgeon to have an expected survival to trial completion (approximately 6 months after implantation), without regard to the likelihood of cardiac transplantation.\n\nExclusion Criteria:\n\n* Exclusion criteria include the presence of a Right Ventricular Assist Device, as biventricular support is associated with decreased survival outcomes that could negatively impact the attrition rate over the course of the study.\n* Additional exclusion criteria include the inability of the patient or a trained caregiver to administer the study drug, and inability of the patient to complete the study questionnaire. - Patients with a creatinine clearance \\< 30 mL/min, evidence of an active infection, immunosuppression, or with an allergy to E. Coli derived products will also be excluded. -\n* Last, any patient with dependence on inflammatory modulating drugs will be excluded.'}, 'identificationModule': {'nctId': 'NCT02547766', 'briefTitle': 'Interleukin-1 Receptor Antagonist for the Treatment of Heart Failure in Patients With Left Ventricular Assist Devices', 'organization': {'class': 'OTHER', 'fullName': 'University of Utah'}, 'officialTitle': 'Interleukin-1 Receptor Antagonist for the Treatment of Heart Failure in Patients With Left Ventricular Assist Devices', 'orgStudyIdInfo': {'id': '75500'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Anakinra Arm', 'description': 'All patients in this arm receive Anakinra in a pre-post design. That is, outcome markers are measured, the intervention (Anakinra) is applied, and the outcome markers are measured again at various intervals to determine effect.', 'interventionNames': ['Drug: Anakinra']}], 'interventions': [{'name': 'Anakinra', 'type': 'DRUG', 'otherNames': ['Kineret'], 'description': 'Anakinra is an Interleukin-1 receptor antagonist that will be given to the patient via subcutaneous injection for a period of 14 consecutive days.', 'armGroupLabels': ['Anakinra Arm']}]}, 'contactsLocationsModule': {'locations': [{'zip': '84132', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': 'University of Utah', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Utah', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'M.D.', 'investigatorFullName': 'Craig Selzman', 'investigatorAffiliation': 'University of Utah'}}}}