{ "FullStudy":{ "Rank":217977, "Study":{ "ProtocolSection":{ "IdentificationModule":{ "NCTId":"NCT01514357", "OrgStudyIdInfo":{ "OrgStudyId":"11-001372" }, "SecondaryIdInfoList":{ "SecondaryIdInfo":[ { "SecondaryId":"UL1RR024150", "SecondaryIdType":"U.S. NIH Grant/Contract", "SecondaryIdLink":"https://projectreporter.nih.gov/reporterapi.cfm?PROJECTNUM=UL1RR024150&Fy=all" } ] }, "Organization":{ "OrgFullName":"Mayo Clinic", "OrgClass":"OTHER" }, "BriefTitle":"Nesiritide in Resistant Hypertension", "OfficialTitle":"Novel Peptides in Resistant Human Hypertension" }, "StatusModule":{ "StatusVerifiedDate":"March 2018", "OverallStatus":"Terminated", "WhyStopped":"Original PI left the institution, and lack of funding.", "ExpandedAccessInfo":{ "HasExpandedAccess":"No" }, "StartDateStruct":{ "StartDate":"April 2012", "StartDateType":"Actual" }, "PrimaryCompletionDateStruct":{ "PrimaryCompletionDate":"July 2014", "PrimaryCompletionDateType":"Actual" }, "CompletionDateStruct":{ "CompletionDate":"July 2014", "CompletionDateType":"Actual" }, "StudyFirstSubmitDate":"January 12, 2012", "StudyFirstSubmitQCDate":"January 20, 2012", "StudyFirstPostDateStruct":{ "StudyFirstPostDate":"January 23, 2012", "StudyFirstPostDateType":"Estimate" }, "ResultsFirstSubmitDate":"April 27, 2017", "ResultsFirstSubmitQCDate":"October 19, 2017", "ResultsFirstPostDateStruct":{ "ResultsFirstPostDate":"October 20, 2017", "ResultsFirstPostDateType":"Actual" }, "LastUpdateSubmitDate":"March 21, 2018", "LastUpdatePostDateStruct":{ "LastUpdatePostDate":"March 23, 2018", "LastUpdatePostDateType":"Actual" } }, "SponsorCollaboratorsModule":{ "ResponsibleParty":{ "ResponsiblePartyType":"Sponsor-Investigator", "ResponsiblePartyInvestigatorFullName":"John C Burnett", "ResponsiblePartyInvestigatorTitle":"Professor of Medicine and Physiology", "ResponsiblePartyInvestigatorAffiliation":"Mayo Clinic" }, "LeadSponsor":{ "LeadSponsorName":"John C Burnett", "LeadSponsorClass":"OTHER" }, "CollaboratorList":{ "Collaborator":[ { "CollaboratorName":"National Center for Research Resources (NCRR)", "CollaboratorClass":"NIH" } ] } }, "OversightModule":{ "OversightHasDMC":"No", "IsFDARegulatedDrug":"Yes", "IsFDARegulatedDevice":"No" }, "DescriptionModule":{ "BriefSummary":"Hypothesis: If the use of B-type natriuretic peptide (BNP) is proven to be effective in controlling high blood pressure, it may lead to a reduction of standard therapy and improved cardiovascular and kidney protection.", "DetailedDescription":"Hypertension remains a global burden in cardiovascular disease leading to stroke, myocardial infarction, and heart failure. Its myocardial complications result from increased mechanical load on the heart. Under physiological conditions of increased myocardial load and resulting myocardial stretch, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) synthesis and secretion occur contributing to maintenance of optimal cardiorenal and blood pressure homeostasis. However, studies indicate that in subjects with cardiovascular diseases the biological structure of these hormones may be altered, thus reducing their favorable protective activities. New studies indicate that early and moderate hypertension is associated with a derangement of the natriuretic peptide system which is characterized by the lack of activation of biologically active ANP and BNP, while severe hypertension is characterized by cardiac release of altered molecular forms of ANP and BNP that have reduced biological properties and/or enhanced degradation.\n\nThe broad objective of proposal is to advance the biology and therapeutics of the natriuretic peptides (NPs) with a special focus on the cardiac peptide BNP in human hypertension. The investigators' proposal is based upon the biological properties of BNP (i.e., natriuretic, renin-angiotensin-aldosterone suppressing, vasodilating, anti-fibrotic, anti-hypertrophic and positive lusitropic), its mechanistic role in human hypertension, and thus its potential as an innovative chronic protein therapeutic to enhance the treatment of patients with uncontrolled and or resistant hypertension. Importantly, BNP is an endocrine hormone normally produced by the human heart, and its use as therapeutic agent has been approved in USA for more than a decade and has been proven to be safe." }, "ConditionsModule":{ "ConditionList":{ "Condition":[ "Hypertension" ] } }, "DesignModule":{ "StudyType":"Interventional", "PhaseList":{ "Phase":[ "Phase 1", "Phase 2" ] }, "DesignInfo":{ "DesignAllocation":"Randomized", "DesignInterventionModel":"Parallel Assignment", "DesignPrimaryPurpose":"Treatment", "DesignMaskingInfo":{ "DesignMasking":"Quadruple", "DesignWhoMaskedList":{ "DesignWhoMasked":[ "Participant", "Care Provider", "Investigator", "Outcomes Assessor" ] } } }, "EnrollmentInfo":{ "EnrollmentCount":"12", "EnrollmentType":"Actual" } }, "ArmsInterventionsModule":{ "ArmGroupList":{ "ArmGroup":[ { "ArmGroupLabel":"Nesiritide (BNP)", "ArmGroupType":"Other", "ArmGroupDescription":"Subjects will receive subcutaneous (SQ) BNP bid for seven consecutive days. The initial starting dose was 5 micrograms/kg.", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: Nesiritide (BNP)" ] } },{ "ArmGroupLabel":"Placebo", "ArmGroupType":"Placebo Comparator", "ArmGroupDescription":"Subjects will receive SQ placebo bid for seven consecutive days.", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: Placebo" ] } } ] }, "InterventionList":{ "Intervention":[ { "InterventionType":"Drug", "InterventionName":"Nesiritide (BNP)", "InterventionDescription":"NATRECOR® (nesiritide) is a sterile, purified preparation of human B-type natriuretic peptide (hBNP), and is manufactured from E. coli using recombinant DNA technology. Each 1.5 mg vial contains a white- to off-white lyophilized powder for intravenous (IV) administration after reconstitution.", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Nesiritide (BNP)" ] }, "InterventionOtherNameList":{ "InterventionOtherName":[ "Natrecor" ] } },{ "InterventionType":"Drug", "InterventionName":"Placebo", "InterventionDescription":"Placebo will be administered subcutaneously instead of active drug (nesiritide) in a blind fashion in the second arm of the study.", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Placebo" ] }, "InterventionOtherNameList":{ "InterventionOtherName":[ "saline solution" ] } } ] } }, "OutcomesModule":{ "PrimaryOutcomeList":{ "PrimaryOutcome":[ { "PrimaryOutcomeMeasure":"Changes in Systolic Blood Pressure (BP)", "PrimaryOutcomeDescription":"The change in BP with treatment over 7 days was assessed by the mean BP on admission, (treatment day 1) mean BP 23 hours after the first injection of BNP, and mean BP 23 hours after the second injection of BNP (treatment day 2). Treatment day 2 was 7 days after admission.", "PrimaryOutcomeTimeFrame":"baseline, treatment day 1, treatment day 2" } ] } }, "EligibilityModule":{ "EligibilityCriteria":"Inclusion criteria:\n\nSubjects with resistant hypertension as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines, systolic blood pressure and/or diastolic blood pressure > 140/90 mm Hg. For patients with hypertension and diabetes or renal disease, blood pressure > 130/80 mm Hg despite treatment with diuretic, sympathetic depressant and vasodilators.\n\nMedications may include a three drug regimen including:\n\ndiuretic at therapeutic dose\na second line agent such as sympatholytic (e.g. beta-blockade, central agent such as clonidine) or angiotensin converting enzyme inhibitor (ACEi) / angiotensin receptor blocker (ARB) or calcium channel blocker (CCB).\nthird line agent including one of the above and/or direct vasodilator, such as hydralazine or minoxidil.\n\nExclusion criteria:\n\nCongestive Heart Failure (any New York Heart Association (NYHA) class)\nEjection Fraction < 50%\nKnown renal artery stenosis\nMyocardial infarction within 3 months of screening\nUnstable angina within 14 days of screening, or any evidence of myocardial ischemia\nModerate to severe pulmonary hypertension\nValvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis, primary pulmonary hypertension, or biopsy proven active myocarditis\nSustained ventricular tachycardia or ventricular fibrillation within 14 days of screening\nSustained Atrial Fibrillation\nSecond or third degree atrioventricular (AV) block without a permanent cardiac pacemaker\nCerebral vascular accident within 3 months of screening, or other evidence of significantly compromised central nervous system perfusion\nTotal bilirubin of > 1.5 mg/dL or aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 1.5 times the upper limit of normal range\nRenal insufficiency assessed by calculated Glomerular Filtration Rate (GFR) < 30 ml/min (Cockcroft-Gault equation)\nSerum sodium of < 125 milliequivalent (mEq)/dL or > 160 mEq/dL\nSerum potassium of < 3.0 mEq/dL or > 5.5 mEq/dL\nWomen taking hormonal contraceptives\nPregnancy\nBody mass index (BMI) > 35", "HealthyVolunteers":"No", "Gender":"All", "MinimumAge":"18 Years", "MaximumAge":"80 Years", "StdAgeList":{ "StdAge":[ "Adult", "Older Adult" ] } }, "ContactsLocationsModule":{ "OverallOfficialList":{ "OverallOfficial":[ { "OverallOfficialName":"John C Burnett, M.D.", "OverallOfficialAffiliation":"Mayo Clinic", "OverallOfficialRole":"Principal Investigator" } ] }, "LocationList":{ "Location":[ { "LocationFacility":"Mayo Clinic in Rochester", "LocationCity":"Rochester", "LocationState":"Minnesota", "LocationZip":"55905", "LocationCountry":"United States" } ] } }, "IPDSharingStatementModule":{ "IPDSharing":"No" } }, "ResultsSection":{ "ParticipantFlowModule":{ "FlowRecruitmentDetails":"Subjects were recruited at Mayo Clinic in Rochester, Minnesota.", "FlowGroupList":{ "FlowGroup":[ { "FlowGroupId":"FG000", "FlowGroupTitle":"Nesiritide (BNP)", "FlowGroupDescription":"Subjects will receive subcutaneous (SQ) BNP bid for seven consecutive days. The initial starting dose was 5 micrograms/kg." },{ "FlowGroupId":"FG001", "FlowGroupTitle":"Placebo", "FlowGroupDescription":"Subjects will receive SQ placebo bid for seven consecutive days." } ] }, "FlowPeriodList":{ "FlowPeriod":[ { "FlowPeriodTitle":"Overall Study", "FlowMilestoneList":{ "FlowMilestone":[ { "FlowMilestoneType":"STARTED", "FlowAchievementList":{ "FlowAchievement":[ { "FlowAchievementGroupId":"FG000", "FlowAchievementNumSubjects":"12" },{ "FlowAchievementGroupId":"FG001", "FlowAchievementNumSubjects":"0" } ] } },{ "FlowMilestoneType":"COMPLETED", "FlowAchievementList":{ "FlowAchievement":[ { "FlowAchievementGroupId":"FG000", "FlowAchievementNumSubjects":"8" },{ "FlowAchievementGroupId":"FG001", "FlowAchievementNumSubjects":"0" } ] } },{ "FlowMilestoneType":"NOT COMPLETED", "FlowAchievementList":{ "FlowAchievement":[ { "FlowAchievementGroupId":"FG000", "FlowAchievementNumSubjects":"4" },{ "FlowAchievementGroupId":"FG001", "FlowAchievementNumSubjects":"0" } ] } } ] }, "FlowDropWithdrawList":{ "FlowDropWithdraw":[ { "FlowDropWithdrawType":"Screen failure", "FlowReasonList":{ "FlowReason":[ { "FlowReasonGroupId":"FG000", "FlowReasonNumSubjects":"2" },{ "FlowReasonGroupId":"FG001", "FlowReasonNumSubjects":"0" } ] } },{ "FlowDropWithdrawType":"Withdrawal by Subject", "FlowReasonList":{ "FlowReason":[ { "FlowReasonGroupId":"FG000", "FlowReasonNumSubjects":"2" },{ "FlowReasonGroupId":"FG001", "FlowReasonNumSubjects":"0" } ] } } ] } } ] } }, "BaselineCharacteristicsModule":{ "BaselineGroupList":{ "BaselineGroup":[ { "BaselineGroupId":"BG000", "BaselineGroupTitle":"Nesiritide (BNP)", "BaselineGroupDescription":"Subjects will receive subcutaneous (SQ) BNP bid for seven consecutive days. The initial starting dose was 5 micrograms/kg." },{ "BaselineGroupId":"BG001", "BaselineGroupTitle":"Placebo", "BaselineGroupDescription":"Subjects will receive SQ placebo bid for seven consecutive days." },{ "BaselineGroupId":"BG002", "BaselineGroupTitle":"Total", "BaselineGroupDescription":"Total of all reporting groups" } ] }, "BaselineDenomList":{ "BaselineDenom":[ { "BaselineDenomUnits":"Participants", "BaselineDenomCountList":{ "BaselineDenomCount":[ { "BaselineDenomCountGroupId":"BG000", "BaselineDenomCountValue":"12" },{ "BaselineDenomCountGroupId":"BG001", "BaselineDenomCountValue":"0" },{ "BaselineDenomCountGroupId":"BG002", "BaselineDenomCountValue":"12" } ] } } ] }, "BaselineMeasureList":{ "BaselineMeasure":[ { "BaselineMeasureTitle":"Age, Categorical", "BaselineMeasureParamType":"Count of Participants", "BaselineMeasureUnitOfMeasure":"Participants", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineCategoryTitle":"<=18 years", "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"0" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"0" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"0" } ] } },{ "BaselineCategoryTitle":"Between 18 and 65 years", "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"12" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"0" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"12" } ] } },{ "BaselineCategoryTitle":">=65 years", "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"0" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"0" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"0" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"Sex: Female, Male", "BaselineMeasureParamType":"Count of Participants", "BaselineMeasureUnitOfMeasure":"Participants", "BaselineClassList":{ "BaselineClass":[ { "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineCategoryTitle":"Female", "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"7" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"0" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"7" } ] } },{ "BaselineCategoryTitle":"Male", "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"5" },{ "BaselineMeasurementGroupId":"BG001", "BaselineMeasurementValue":"0" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"5" } ] } } ] } } ] } },{ "BaselineMeasureTitle":"Region of Enrollment", "BaselineMeasureParamType":"Number", "BaselineMeasureUnitOfMeasure":"participants", "BaselineClassList":{ "BaselineClass":[ { "BaselineClassTitle":"United States", "BaselineCategoryList":{ "BaselineCategory":[ { "BaselineMeasurementList":{ "BaselineMeasurement":[ { "BaselineMeasurementGroupId":"BG000", "BaselineMeasurementValue":"12" },{ "BaselineMeasurementGroupId":"BG002", "BaselineMeasurementValue":"12" } ] } } ] } } ] } } ] } }, "OutcomeMeasuresModule":{ "OutcomeMeasureList":{ "OutcomeMeasure":[ { "OutcomeMeasureType":"Primary", "OutcomeMeasureTitle":"Changes in Systolic Blood Pressure (BP)", "OutcomeMeasureDescription":"The change in BP with treatment over 7 days was assessed by the mean BP on admission, (treatment day 1) mean BP 23 hours after the first injection of BNP, and mean BP 23 hours after the second injection of BNP (treatment day 2). Treatment day 2 was 7 days after admission.", "OutcomeMeasureReportingStatus":"Posted", "OutcomeMeasureParamType":"Mean", "OutcomeMeasureDispersionType":"Standard Deviation", "OutcomeMeasureUnitOfMeasure":"mmHg", "OutcomeMeasureTimeFrame":"baseline, treatment day 1, treatment day 2", "OutcomeGroupList":{ "OutcomeGroup":[ { "OutcomeGroupId":"OG000", "OutcomeGroupTitle":"Nesiritide (BNP)", "OutcomeGroupDescription":"Subjects will receive subcutaneous (SQ) Nesiritide (BNP) bid for seven consecutive days. The initial starting dose was 5 micrograms/kg." },{ "OutcomeGroupId":"OG001", "OutcomeGroupTitle":"Placebo", "OutcomeGroupDescription":"Subjects will receive SQ placebo bid for seven consecutive days." } ] }, "OutcomeDenomList":{ "OutcomeDenom":[ { "OutcomeDenomUnits":"Participants", "OutcomeDenomCountList":{ "OutcomeDenomCount":[ { "OutcomeDenomCountGroupId":"OG000", "OutcomeDenomCountValue":"8" },{ "OutcomeDenomCountGroupId":"OG001", "OutcomeDenomCountValue":"0" } ] } } ] }, "OutcomeClassList":{ "OutcomeClass":[ { "OutcomeClassTitle":"Baseline", "OutcomeCategoryList":{ "OutcomeCategory":[ { "OutcomeMeasurementList":{ "OutcomeMeasurement":[ { "OutcomeMeasurementGroupId":"OG000", "OutcomeMeasurementValue":"153", "OutcomeMeasurementSpread":"9.180" } ] } } ] } },{ "OutcomeClassTitle":"Treatment Day 1", "OutcomeCategoryList":{ "OutcomeCategory":[ { "OutcomeMeasurementList":{ "OutcomeMeasurement":[ { "OutcomeMeasurementGroupId":"OG000", "OutcomeMeasurementValue":"134", "OutcomeMeasurementSpread":"9.07" } ] } } ] } },{ "OutcomeClassTitle":"Treatment Day 2", "OutcomeCategoryList":{ "OutcomeCategory":[ { "OutcomeMeasurementList":{ "OutcomeMeasurement":[ { "OutcomeMeasurementGroupId":"OG000", "OutcomeMeasurementValue":"129", "OutcomeMeasurementSpread":"17.34" } ] } } ] } } ] } } ] } }, "AdverseEventsModule":{ "EventsFrequencyThreshold":"0", "EventsTimeFrame":"7 days", "EventGroupList":{ "EventGroup":[ { "EventGroupId":"EG000", "EventGroupTitle":"Nesiritide (BNP)", "EventGroupDescription":"Subjects will receive subcutaneous (SQ) BNP bid for seven consecutive days. The initial starting dose was 5 micrograms/kg.", "EventGroupDeathsNumAffected":"0", "EventGroupDeathsNumAtRisk":"8", "EventGroupSeriousNumAffected":"0", "EventGroupSeriousNumAtRisk":"8", "EventGroupOtherNumAffected":"0", "EventGroupOtherNumAtRisk":"8" },{ "EventGroupId":"EG001", "EventGroupTitle":"Placebo", "EventGroupDescription":"Subjects will receive SQ placebo bid for seven consecutive days.", "EventGroupDeathsNumAffected":"0", "EventGroupDeathsNumAtRisk":"0", "EventGroupSeriousNumAffected":"0", "EventGroupSeriousNumAtRisk":"0", "EventGroupOtherNumAffected":"0", "EventGroupOtherNumAtRisk":"0" } ] } }, "MoreInfoModule":{ "LimitationsAndCaveats":{}, "CertainAgreement":{ "AgreementPISponsorEmployee":"Yes" }, "PointOfContact":{ "PointOfContactTitle":"Dr. John C. Burnett", "PointOfContactOrganization":"Mayo Clinic", "PointOfContactEMail":"burnett.john@mayo.edu", "PointOfContactPhone":"507-284-7932" } } }, "DerivedSection":{ "MiscInfoModule":{ "VersionHolder":"April 22, 2020" }, "InterventionBrowseModule":{ "InterventionMeshList":{ "InterventionMesh":[ { "InterventionMeshId":"D000020097", "InterventionMeshTerm":"Natriuretic Peptide, Brain" } ] }, "InterventionAncestorList":{ "InterventionAncestor":[ { "InterventionAncestorId":"D000045283", "InterventionAncestorTerm":"Natriuretic Agents" },{ "InterventionAncestorId":"D000045505", "InterventionAncestorTerm":"Physiological Effects of Drugs" } ] }, "InterventionBrowseLeafList":{ "InterventionBrowseLeaf":[ { "InterventionBrowseLeafId":"M20444", "InterventionBrowseLeafName":"Pharmaceutical Solutions", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M20519", "InterventionBrowseLeafName":"Natriuretic Peptide, Brain", "InterventionBrowseLeafAsFound":"Nesiritide", "InterventionBrowseLeafRelevance":"high" } ] }, "InterventionBrowseBranchList":{ "InterventionBrowseBranch":[ { "InterventionBrowseBranchAbbrev":"All", "InterventionBrowseBranchName":"All Drugs and Chemicals" },{ "InterventionBrowseBranchAbbrev":"NaAg", "InterventionBrowseBranchName":"Natriuretic Agents" } ] } }, "ConditionBrowseModule":{ "ConditionMeshList":{ "ConditionMesh":[ { "ConditionMeshId":"D000006973", "ConditionMeshTerm":"Hypertension" } ] }, "ConditionAncestorList":{ "ConditionAncestor":[ { "ConditionAncestorId":"D000014652", "ConditionAncestorTerm":"Vascular Diseases" },{ "ConditionAncestorId":"D000002318", "ConditionAncestorTerm":"Cardiovascular Diseases" } ] }, "ConditionBrowseLeafList":{ "ConditionBrowseLeaf":[ { "ConditionBrowseLeafId":"M8607", "ConditionBrowseLeafName":"Hypertension", "ConditionBrowseLeafAsFound":"Hypertension", "ConditionBrowseLeafRelevance":"high" },{ "ConditionBrowseLeafId":"M15983", "ConditionBrowseLeafName":"Vascular Diseases", "ConditionBrowseLeafRelevance":"low" } ] }, "ConditionBrowseBranchList":{ "ConditionBrowseBranch":[ { "ConditionBrowseBranchAbbrev":"BC14", "ConditionBrowseBranchName":"Heart and Blood Diseases" },{ "ConditionBrowseBranchAbbrev":"All", "ConditionBrowseBranchName":"All Conditions" } ] } } } } } }