Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06613477
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-23
Brief Title:
PKPD of Digoxin in Infants With SVHD
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Pharmacokinetics and Pharmacodynamics of Digoxin in Infants With Single Ventricle Heart Disease
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary participant will be an infant with single ventricle heart disease
This 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
The 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
Being 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
This 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
The 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
Being 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
Detailed Description:
Study design Multi-center prospective open-label opportunistic PKPD study of digoxin
Randomization 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
Table 1 PK sample collection times PK Sample Sample window for plasma collection
1 8 - 115 hours after dose trough level on dosing Day 7 - 2 days
2 15 minutes - 1 hour after dose on dosing Day 14
3 2 - 5 hours after dose on dosing Day 14
4 8 - 115 hours after dose trough level on dosing Day 14
5 - 7 8 - 115 hours after dose trough level on any dosing Day 14 and 180 or Day of S2P
PK 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 - 115 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
Table 2 PD sample collection times PD Sample Sample window for plasma collection
1 Within 24 hours prior to first digoxin dose
2 Any time on dosing day 28 - 7 days
3 Any time on dosing day 112 - 7 days
4 Any time within 7 days prior to S2P
PD sampling plasma samples for NT-proBNP and MR-proANP quantification will be collected according to Table 2
Safety 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
Cardiac assessments records of echocardiograms and cardiac catheterizations performed per standard of care will be collected
This study will be conducted in accordance with current US 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
Scientific 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
Rationale 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 Cminss of 05 - 2 ngmL 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
Randomization 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
Table 1 PK sample collection times PK Sample Sample window for plasma collection
1 8 - 115 hours after dose trough level on dosing Day 7 - 2 days
2 15 minutes - 1 hour after dose on dosing Day 14
3 2 - 5 hours after dose on dosing Day 14
4 8 - 115 hours after dose trough level on dosing Day 14
5 - 7 8 - 115 hours after dose trough level on any dosing Day 14 and 180 or Day of S2P
PK 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 - 115 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
Table 2 PD sample collection times PD Sample Sample window for plasma collection
1 Within 24 hours prior to first digoxin dose
2 Any time on dosing day 28 - 7 days
3 Any time on dosing day 112 - 7 days
4 Any time within 7 days prior to S2P
PD sampling plasma samples for NT-proBNP and MR-proANP quantification will be collected according to Table 2
Safety 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
Cardiac assessments records of echocardiograms and cardiac catheterizations performed per standard of care will be collected
This study will be conducted in accordance with current US 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
Scientific 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
Rationale 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 Cminss of 05 - 2 ngmL 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None