Nctid:
NCT06613477
Payload:
{"hasResults"=>false, "derivedSection"=>{"miscInfoModule"=>{"versionHolder"=>"2024-10-04"}, "conditionBrowseModule"=>{"meshes"=>[{"id"=>"D000080039", "term"=>"Univentricular Heart"}, {"id"=>"D000007232", "term"=>"Infant, Newborn, Diseases"}, {"id"=>"D000007235", "term"=>"Infant, Premature, Diseases"}], "ancestors"=>[{"id"=>"D000006330", "term"=>"Heart Defects, Congenital"}, {"id"=>"D000018376", "term"=>"Cardiovascular Abnormalities"}, {"id"=>"D000002318", "term"=>"Cardiovascular Diseases"}, {"id"=>"D000006331", "term"=>"Heart Diseases"}, {"id"=>"D000000013", "term"=>"Congenital Abnormalities"}], "browseLeaves"=>[{"id"=>"M25869", "name"=>"Premature Birth", "relevance"=>"LOW"}, {"id"=>"M9419", "name"=>"Heart Diseases", "relevance"=>"LOW"}, {"id"=>"M10276", "name"=>"Infant, Newborn, Diseases", "asFound"=>"Infant, Newborn, Diseases", "relevance"=>"HIGH"}, {"id"=>"M10279", "name"=>"Infant, Premature, Diseases", "asFound"=>"Infant, Premature, Diseases", "relevance"=>"HIGH"}, {"id"=>"M2100", "name"=>"Univentricular Heart", "asFound"=>"Single Ventricle", "relevance"=>"HIGH"}, {"id"=>"M9418", "name"=>"Heart Defects, Congenital", "relevance"=>"LOW"}, {"id"=>"M12", "name"=>"Congenital Abnormalities", "relevance"=>"LOW"}, {"id"=>"M20503", "name"=>"Cardiovascular Abnormalities", "relevance"=>"LOW"}, {"id"=>"T5247", "name"=>"Single Ventricular Heart", "asFound"=>"Single Ventricle", "relevance"=>"HIGH"}], "browseBranches"=>[{"name"=>"Urinary Tract, Sexual Organs, and Pregnancy Conditions", "abbrev"=>"BXS"}, {"name"=>"All Conditions", "abbrev"=>"All"}, {"name"=>"Heart and Blood Diseases", "abbrev"=>"BC14"}, {"name"=>"Diseases and Abnormalities at or Before Birth", "abbrev"=>"BC16"}, {"name"=>"Rare Diseases", "abbrev"=>"Rare"}]}, "interventionBrowseModule"=>{"meshes"=>[{"id"=>"D000004077", "term"=>"Digoxin"}], "ancestors"=>[{"id"=>"D000000889", "term"=>"Anti-Arrhythmia Agents"}, {"id"=>"D000002316", "term"=>"Cardiotonic Agents"}, {"id"=>"D000004791", "term"=>"Enzyme Inhibitors"}, {"id"=>"D000045504", "term"=>"Molecular Mechanisms of Pharmacological Action"}, {"id"=>"D000020011", "term"=>"Protective Agents"}, {"id"=>"D000045505", "term"=>"Physiological Effects of Drugs"}], "browseLeaves"=>[{"id"=>"M7265", "name"=>"Digoxin", "asFound"=>"Short-term", "relevance"=>"HIGH"}, {"id"=>"M7992", "name"=>"Epinephrine", "relevance"=>"LOW"}, {"id"=>"M30371", "name"=>"Racepinephrine", "relevance"=>"LOW"}, {"id"=>"M211043", "name"=>"Epinephryl borate", "relevance"=>"LOW"}, {"id"=>"M4213", "name"=>"Anti-Arrhythmia Agents", "relevance"=>"LOW"}, {"id"=>"M5572", "name"=>"Cardiotonic Agents", "relevance"=>"LOW"}, {"id"=>"M7951", "name"=>"Enzyme Inhibitors", "relevance"=>"LOW"}, {"id"=>"M21869", "name"=>"Protective Agents", "relevance"=>"LOW"}], "browseBranches"=>[{"name"=>"Anti-Arrhythmia Agents", "abbrev"=>"AnArAg"}, {"name"=>"Cardiotonic Agents", "abbrev"=>"CaAg"}, {"name"=>"All Drugs and Chemicals", "abbrev"=>"All"}, {"name"=>"Vasoconstrictor Agents", "abbrev"=>"VaCoAg"}, {"name"=>"Respiratory System Agents", "abbrev"=>"Resp"}]}}, "protocolSection"=>{"designModule"=>{"phases"=>["PHASE1", "PHASE2"], "studyType"=>"INTERVENTIONAL", "designInfo"=>{"allocation"=>"NA", "maskingInfo"=>{"masking"=>"NONE"}, "primaryPurpose"=>"TREATMENT", "interventionModel"=>"SINGLE_GROUP", "interventionModelDescription"=>"Each subject will receive population specific PK model-derived digoxin dosing."}, "enrollmentInfo"=>{"type"=>"ESTIMATED", "count"=>20}}, "statusModule"=>{"overallStatus"=>"NOT_YET_RECRUITING", "startDateStruct"=>{"date"=>"2024-10-01", "type"=>"ESTIMATED"}, "expandedAccessInfo"=>{"hasExpandedAccess"=>false}, "statusVerifiedDate"=>"2024-09", "completionDateStruct"=>{"date"=>"2025-12-31", "type"=>"ESTIMATED"}, "lastUpdateSubmitDate"=>"2024-09-23", "studyFirstSubmitDate"=>"2024-09-23", "studyFirstSubmitQcDate"=>"2024-09-23", "lastUpdatePostDateStruct"=>{"date"=>"2024-09-26", "type"=>"ACTUAL"}, "studyFirstPostDateStruct"=>{"date"=>"2024-09-26", "type"=>"ACTUAL"}, "primaryCompletionDateStruct"=>{"date"=>"2025-12-31", "type"=>"ESTIMATED"}}, "outcomesModule"=>{"primaryOutcomes"=>[{"measure"=>"Digoxin plasma concentration", "timeFrame"=>"End of study, up to 180 Days", "description"=>"Plasma concentrations of digoxin over time measured using a validated bioanalytical assay at a central laboratory to calculate clearance and area under the curve (AUC)"}]}, "oversightModule"=>{"isUsExport"=>false, "oversightHasDmc"=>false, "isFdaRegulatedDrug"=>true, "isFdaRegulatedDevice"=>false}, "conditionsModule"=>{"keywords"=>["Infants", "SVD", "SVHD", "Single Ventricle", "Digoxin", "Pharmacokinetics", "Pharmacodynamics", "PK", "PD"], "conditions"=>["Single-ventricle", "Infant Conditions", "Infant, Newborn, Diseases", "Infant, Premature, Diseases"]}, "descriptionModule"=>{"briefSummary"=>"The primary participant will be an infant with single ventricle heart disease.\n\nThis is a research study to learn more about how the medication digoxin, which is routinely prescribed to infants and children with heart disease in pediatric cardiac intensive care units is processed by their bodies and how it may help their cardiac function.\n\nThe investigators will collect blood or will collect blood samples when bloodwork is checked as part of regular care (\"opportunistic\"). The investigators will also collect information from medical records.\n\nBeing part of this study will not change treatment plan or medications. The risks of this study include loss of confidentiality and risks associated with having blood drawn. The study team will make every effort to minimize these risks.", "detailedDescription"=>"Study design: Multi-center, prospective, open-label, opportunistic PK/PD study of digoxin.\n\nRandomization: none Blinding /Masking: none Study intervention: Each subject will receive population specific PK model-derived digoxin dosing Duration of participant participation: up to 180 days\n\nTable 1. PK sample collection times PK Sample # Sample window for plasma collection\n\n1. 8 - 11.5 hours after dose / trough level on dosing Day 7 (+/- 2 days)\n2. 15 minutes - 1 hour after dose on dosing Day ≥14\n3. 2 - 5 hours after dose on dosing Day ≥14\n4. 8 - 11.5 hours after dose / trough level on dosing Day ≥14\n5. - 7\\* 8 - 11.5 hours after dose / trough level on any dosing Day ≥14 and ≤180 or Day of S2P\n\nPK sampling: digoxin concentrations in plasma will be measured at a central lab using validated bioanalytical assays. Plasma samples for digoxin quantification will be drawn according to Table 1. Initial PK sample will be obtained once on dosing Day 7 (+/- 2 days). PK samples 2-4 will be obtained once on dosing day ≥14. Every effort will be made to collect samples 2-4 after the same digoxin dose. Up to 3 additional samples will be collected 8 - 11.5 hours after dosing on different dosing days ≥14 but ≤180 or day of S2P, whichever occurs first. Samples 5 - 7 will be collected on different days.\n\nTable 2. PD sample collection times PD Sample # Sample window for plasma collection\n\n1. Within 24 hours prior to first digoxin dose\n2. Any time on dosing day 28 (+/- 7 days)\n3. Any time on dosing day 112 (+/- 7 days)\n4. Any time within 7 days prior to S2P\n\nPD sampling: plasma samples for NT-proBNP and MR-proANP quantification will be collected according to Table 2.\n\nSafety: Adverse events related to the study procedure (sample collection, blood draws and outcome assessments), adverse events related to digoxin, select events of special interest (tachyarrythmias, second and third degree atrioventricular conduction block, sinus bradycardia, need for temporary or permanent pacing, death), and serious, unexpected, suspected adverse reactions (SUSARs) related to digoxin will be captured.\n\nCardiac assessments: records of echocardiograms and cardiac catheterizations performed per standard of care will be collected.\n\nThis study will be conducted in accordance with current U.S. Food and Drug Administration regulations and guidelines, (or, as applicable, the European Clinical Trials Directive and associated guidelines), the International Conference on Harmonisation Guidelines on Good Clinical Practice (which incorporate the principles of the Declaration of Helsinki), as well as all other applicable national and local laws and regulations.\n\nScientific Rationale for Study Design This study is designed to prospectively validate the PK model-derived dosing of digoxin in infants with single ventricle CHD after S1P but before S2P. A validation trial is necessary to confirm that the weight, age, and estimated glomerular filtration rate based dosing regimen is able to achieve digoxin exposures consistent with the package insert recommendations.\n\nRationale for Dose Selection A population PK model of digoxin was developed in a cohort of 50 infants with single ventricle CHD treated with digoxin after S1P but prior to S2P. A 2 compartment model with transit compartment absorption best described the digoxin disposition in this population. Body weight and estimated glomerular filtration rate were covariates retained in the model, The model was applied to dosing simulations targeting a Cmin,ss of 0.5 - 2 ng/mL, as recommended by the digoxin package insert. Doses recommended by the model are lower than doses recommended by the current digoxin package insert, and lower that the doses received in the PTN DGX01 trial."}, "eligibilityModule"=>{"sex"=>"ALL", "stdAges"=>["CHILD"], "maximumAge"=>"6 months", "minimumAge"=>"30 days", "healthyVolunteers"=>false, "eligibilityCriteria"=>"Inclusion Criteria:\n\n1. Diagnosis of single ventricle congenital heart disease\n2. Status post-surgical or hybrid stage 1 palliation but prior to surgical stage 2 palliation\n3. Age ≤ 30 days of life at time of stage 1 palliation\n4. Age \\< 6 months at time of enrollment\n5. Require treatment with enteral digoxin per their treating medical provider\n6. Informed consent obtained from parent(s) or legal guardian(s)\n\nExclusion Criteria:\n\n1. Prematurity (gestational age \\<37 weeks) at birth\n2. Serum creatinine \\> 2 mg/dL at enrollment\n3. Diagnosis of second degree or higher atrioventricular conduction block at enrollment\n4. Diagnosis of clinically significant sinus bradycardia requiring intervention at enrollment\n5. Known hypersensitivity to digoxin or other forms of digitalis\n6. Extracorporeal life support (i.e., ECMO, dialysis, ventricular assist device) at enrollment\n7. Received digoxin prior to enrollment"}, "identificationModule"=>{"nctId"=>"NCT06613477", "briefTitle"=>"PK/PD of Digoxin in Infants With SVHD", "organization"=>{"class"=>"OTHER", "fullName"=>"Duke University"}, "officialTitle"=>"Pharmacokinetics and Pharmacodynamics of Digoxin in Infants With Single Ventricle Heart Disease", "orgStudyIdInfo"=>{"id"=>"Pro00113213"}, "secondaryIdInfos"=>[{"id"=>"1R01HD106588-01A1", "link"=>"https://reporter.nih.gov/quickSearch/1R01HD106588-01A1", "type"=>"NIH"}]}, "armsInterventionsModule"=>{"armGroups"=>[{"type"=>"EXPERIMENTAL", "label"=>"Population specific PK model-derived digoxin dosing", "description"=>"Digoxin elixir will be used to dose enterally every 12 hours.\n\nThe dosage will be determined by the protocol PK model. Dosing is to be administered based on weight, postnatal age, and estimated glomerular filtration rate\n\nThe duration of the participation could be up to 180 days. Day 1 to S2P or Day 180 (+/- 7)", "interventionNames"=>["Drug: PK/PD Model Based Dosing of Digoxin in Infants with Single Ventricle Heart Disease"]}], "interventions"=>[{"name"=>"PK/PD Model Based Dosing of Digoxin in Infants with Single Ventricle Heart Disease", "type"=>"DRUG", "otherNames"=>["Lanoxin"], "description"=>"Table 3: Digoxin dosing regimen based on optimized Cmin,ss Dose to be given twice daily (mcg/kg/dose) PNA\\<30 days 30 days \\< PNA \\< 180 days eGFR≤40 1.4 1.4 40\\<eGFR≤60 1.6 1.6 eGFR\\>60 1.9 2.8", "armGroupLabels"=>["Population specific PK model-derived digoxin dosing"]}]}, "contactsLocationsModule"=>{"locations"=>[{"zip"=>"27701", "city"=>"Durham", "state"=>"North Carolina", "country"=>"United States", "contacts"=>[{"name"=>"Elizabeth Thompson, MD", "role"=>"CONTACT", "email"=>"liz.thompson@duke.edu"}], "facility"=>"Duke University Medical Center", "geoPoint"=>{"lat"=>35.99403, "lon"=>-78.89862}}, {"zip"=>"29425", "city"=>"Charleston", "state"=>"South Carolina", "country"=>"United States", "contacts"=>[{"name"=>"Eric Graham, MD", "role"=>"CONTACT", "email"=>"grahamem@musc.edu"}], "facility"=>"Medical University of South Carolina", "geoPoint"=>{"lat"=>32.77657, "lon"=>-79.93092}}], "centralContacts"=>[{"name"=>"Alex Hammett, BS/BA", "role"=>"CONTACT", "email"=>"Alex.Hammett@duke.edu", "phone"=>"919-668-8432"}], "overallOfficials"=>[{"name"=>"Christoph Hornik, MD", "role"=>"PRINCIPAL_INVESTIGATOR", "affiliation"=>"Duke Clinical Research Institute"}]}, "ipdSharingStatementModule"=>{"ipdSharing"=>"NO"}, "sponsorCollaboratorsModule"=>{"leadSponsor"=>{"name"=>"Duke University", "class"=>"OTHER"}, "collaborators"=>[{"name"=>"Medical University of South Carolina", "class"=>"OTHER"}, {"name"=>"Duke Clinical Research Institute", "class"=>"OTHER"}, {"name"=>"National Center for Child Health and Development (NICHD)", "class"=>"UNKNOWN"}, {"name"=>"Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)", "class"=>"NIH"}], "responsibleParty"=>{"type"=>"SPONSOR"}}}}
