PK/PD of Digoxin in Infants With SVHD

NCT ID: NCT06613477

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-10
• Study Completion Date: 2026-11-30

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

1. 8 - 11.5 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 - 11.5 hours after dose / trough level on dosing Day ≥14

5. - 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.

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 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.

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 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.

Conditions

Single-ventricle; Infant Conditions; Infant, Newborn, Diseases; Infant, Premature, Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

PK/PD Model Based Dosing of Digoxin in Infants with Single Ventricle Heart Disease

Intervention Type: DRUG

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

Interventions

PK/PD Model Based Dosing of Digoxin in Infants with Single Ventricle Heart Disease

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

Intervention Type: DRUG

Other Intervention Names

Lanoxin

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of single ventricle congenital heart disease

2. Status post-surgical or hybrid stage 1 palliation but prior to surgical stage 2 palliation

3. Age ≤ 30 days of life at time of stage 1 palliation

4. Age < 6 months at time of enrollment

5. Require treatment with enteral digoxin per their treating medical provider

6. Informed consent obtained from parent(s) or legal guardian(s)

Exclusion Criteria

1. Prematurity (gestational age <37 weeks) at birth

2. Serum creatinine > 2 mg/dL at enrollment

3. Diagnosis of second degree or higher atrioventricular conduction block at enrollment

4. Diagnosis of clinically significant sinus bradycardia requiring intervention at enrollment

5. Known hypersensitivity to digoxin or other forms of digitalis

6. Extracorporeal life support (i.e., ECMO, dialysis, ventricular assist device) at enrollment

7. Received digoxin prior to enrollment

• Minimum Eligible Age: 30 Days
• Maximum Eligible Age: 6 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: collaborator

Duke Clinical Research Institute

OTHER

Sponsor Role: collaborator

National Center for Child Health and Development (NICHD)

UNKNOWN

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christoph Hornik, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Locations

Duke University Medical Center

Durham, North Carolina, United States

Site Status: RECRUITING

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status: NOT_YET_RECRUITING

Countries

United States

Central Contacts

Alex Hammett, BS/BA

Role: CONTACT

Alex.Hammett@duke.edu

919-668-8432

Facility Contacts

Elizabeth Thompson, MD

Role: primary

liz.thompson@duke.edu

Eric Graham, MD

Role: primary

grahamem@musc.edu

Other Identifiers

1R01HD106588-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00113213

Identifier Type: -

Identifier Source: org_study_id