Congenital Heart Disease
Conditions
Brief summary
This is a prospective, multi-center, open-label, PK and safety profile study of enteral digoxin in children \<6 months old at time of enrollment, post-surgical or hybrid stage 1 palliation, but prior to surgical stage 2 palliation.
Detailed description
The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) funded this protocol titled Pharmacokinetics and Safety Profile of Digoxin in Infants with Single Ventricle Congenital Heart Disease, protocol number NICHD-2018-DGX01. The Investigational New Drug (IND) Sponsor and Principal Investigator for this protocol is Christopher P. Hornik, MD, MPH. The Contracting Officer's Technical Representative (COTR) to represent the Government for this task order is Perdita Taylor-Zapata. The Duke IRB number for this study is Pro00102130. This study employs a central IRB, the WIRB-Copernicus Group (WCG). The c-IRB (WCG) study number is 20190888 / NICHD-2018-DGX01. This is a prospective, multicenter Phase 1 study with a primary objective to characterize the pharmacokinetics of enteral digoxin in infants with single ventricle congenital heart disease. The secondary objective is to determine the safety profile of enteral digoxin in infants with single ventricle congenital heart disease. Digoxin is used for the treatment of heart failure in pediatric patients and acts by controlling numerous functions of the cardiovascular system. Digoxin use in single ventricle congenital heart disease may decrease interstage mortality. The study will be conducted in approximately 48 subjects at approximately 13 investigational centers. The proposed duration of the study is approximately 196 (±) days. Please see the protocol and synopsis for more information.
Interventions
DRUGDigoxin
Drug administered per standard of care, with a dosing regimen within the labeled dose range of 7.5-20 mcg/kg/day divided in 2 or 3 equal doses
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
The Emmes Company, LLC
Christoph P Hornik, MD MPH
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 6 Months
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 if their planned maintenance treatment dosing regimen is within the labeled dose range of 7.5 - 20 mcg/kg/day divided in 2 or 3 equal doses * Informed consent from parent(s) or legal guardian(s)
Exclusion criteria
* 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 * Received or anticipated to receive a loading dose of digoxin. * Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentrations of digoxin | Approximately 7 months | The primary outcome measures are plasma concentrations of digoxin measured using a validated bioanalytical assay at a central laboratory. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tachyarrthmias | Approximately 7 months | Event of special interest will be captured (number of tachyarrythmias) |
| Number of participants with second and third degree atrioventricular conduction block | Approximately 7 months | — |
| Number of participants with sinus bradycardia | Approximately 7 months | Number of participants with sinus bradycardia |
| Number of participants with need for temporary or permanent pacing | Approximately 7 months | Number of participants with need for temporary or permanent pacing |
| Number of adverse events related to study procedures and serious, unexpected, suspected adverse reactions related to digoxin | Approximately 7 months | 1\. Adverse events (AEs) related to the study procedures (blood draws and outcome assessments), and serious, unexpected, suspected adverse reactions (SUSARs) related to digoxin will be captured. |
| PR interval | Approximately 7 months | Derived from electrocardiograms and their reports performed per standard of care |
| QRS duration | Approximately 7 months | Derived from electrocardiograms and their reports performed per standard of care |
| QT interval | Approximately 7 months | Derived from electrocardiograms and their reports performed per standard of care |
| Corrected QT interval using Bazett's formula | Approximately 7 months | Derived from electrocardiograms and their reports performed per standard of care |
| Frequency of death | Approximately 7 months | Frequency of death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cardiac output | Approximately 7 months | As measured by cardiac catheterization |
| Pulmonary to systemic blood flow ratio | Approximately 7 months | As measured by cardiac catheterization |
| Pulmonary vascular resistance | Approximately 7 months | As measured by cardiac catheterization |
| Mean pulmonary artery pressure | Approximately 7 months | As measured by cardiac catheterization |
| Right ventricular or left ventricular end diastolic pressure | Approximately 7 months | As measured by cardiac catheterization |
| Right ventricular or left ventricular end systolic pressure | Approximately 7 months | As measured by cardiac catheterization |
| Right and left pulmonary artery size | Approximately 7 months | As measured by cardiac catheterization |
| Plasma concentration of NT-proBNP | Approximately 7 months | — |
| Incidence of unplanned surgical intervention | Approximately 7 months | Including cannulation for mechanical circulatory support |
| Incidence of listing for heart transplant | Approximately 7 months | — |
| Incidence of receiving heart transplant | Approximately 7 months | — |
| Hospital length of stay after S1P | Approximately 7 months | — |
| Number of days on mechanical ventilation after S1P | Approximately 7 months | — |
| Number of hospital readmissions from S1P discharge to S2p | Approximately 7 months | — |
| Pressure gradients across the aortic arch | Approximately 7 months | As measured by cardiac catheterization |
| Plasma concentration of MR-proANP | Approximately 7 months | — |
| Right ventricular or left ventricular end diastolic volume | Approximately 7 months | — |
| Right ventricular or left ventricular end systolic volume | Approximately 7 months | — |
| Right ventricular or left ventricular ejection fraction | Approximately 7 months | — |
| Right ventricular or left ventricular shortening fraction | Approximately 7 months | — |
| Right ventricular or left ventricular end diastolic dimension | Approximately 7 months | — |
| Right ventricular or left ventricular end systolic dimension | Approximately 7 months | — |
| Right ventricular or left ventricular fractional area change | Approximately 7 months | — |
| Degree of atrioventricular valve regurgitation | Approximately 7 months | — |
| Qualitative right ventricular or left ventricular function assessment | Approximately 7 months | — |
Countries
United States
Outcome results
None listed