Pharmacokinetics and Pharmacodynamics of Digoxin in Infants With Single Ventricle Heart Disease
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 24
- Locations
- 2
- Primary Endpoint
- Digoxin plasma concentration
Study Overview
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.
Detailed Description
Study design: Multi-center, prospective, open-label, opportunistic PK/PD 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
- 8 - 11.5 hours after dose / trough level on dosing Day 7 (+/- 2 days)
- 15 minutes - 1 hour after dose on dosing Day ≥14
- 2 - 5 hours after dose on dosing Day ≥14
- 8 - 11.5 hours after dose / trough level on dosing Day ≥14
- - 7* 8 - 11.5 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 - 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 30 Days to 6 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Diagnosis of single ventricle congenital heart disease
- •Status post-surgical or hybrid stage 1 palliation but prior to surgical stage 2 palliation
- •Age ≤ 30 days of life at time of stage 1 palliation
- •Age < 6 months at time of enrollment
- •Require treatment with enteral digoxin per their treating medical provider
- •Informed consent obtained from parent(s) or legal guardian(s)
Exclusion Criteria
- •Gestational age at birth <35 weeks
- •Serum creatinine > 2 mg/dL at enrollment
- •Diagnosis of second degree or higher atrioventricular conduction block at enrollment
- •Diagnosis of clinically significant sinus bradycardia requiring intervention at enrollment
- •Known hypersensitivity to digoxin or other forms of digitalis
- •Extracorporeal life support (i.e., ECMO, dialysis, ventricular assist device) at enrollment
- •Received digoxin prior to enrollment
- •Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
Arms & Interventions
Population specific PK model-derived digoxin dosing
Digoxin elixir will be used to dose enterally every 12 hours.
The dosage will be determined by the protocol PK model. Dosing is to be administered based on weight, postnatal age, and estimated glomerular filtration rate
The duration of the participation could be up to 180 days. Day 1 to S2P or Day 180 (+/- 7)
Intervention: PK/PD Model Based Dosing of Digoxin in Infants with Single Ventricle Heart Disease (Drug)
Outcomes
Primary Outcomes
Digoxin plasma concentration
Time Frame: End of study, up to 180 Days
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)
Secondary Outcomes
No secondary outcomes reported