Pharmacokinetics and Safety Profile of Digoxin in Infants With Single Ventricle Congenital Heart Disease

Congenital Heart Disease Clinical Trial

— DGX01  

Official title:

Pharmacokinetics and Safety Profile of Digoxin in Infants With Single Ventricle Congenital Heart Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03877965
• Other study ID #: Pro00102130
• Secondary ID: NICHD-2018-DGX01
• Status: Completed
• Start date: August 5, 2019
• Est. completion date: January 17, 2022

Study information

• Verified date: October 2022
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: January 17, 2022
• Est. primary completion date: July 13, 2021
• Gender: All
• Age group: N/A to 6 Months

Eligibility

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

Related Conditions & MeSH terms

• Congenital Heart Disease
• Heart Defects, Congenital
• Heart Diseases
• Univentricular Heart

Intervention

Drug:
• Digoxin
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

Locations

Country	Name	City	State
United States	The Children's Hospital Colorado	Aurora	Colorado
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Children's Memorial Hermann Hospital	Houston	Texas
United States	Mattel Children's Hospital at UCLA	Los Angeles	California
United States	Nicklaus Children's Hospital	Miami	Florida
United States	Morgan Stanley Children's Hospital of New York Presbyterian	New York	New York
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Rady Childrens Hospital and Health Center	San Diego	California
United States	Alfred I. DuPont Hospital for Children	Wilmington	Delaware

Sponsors (3)

Lead Sponsor	Collaborator
Christoph P Hornik, MD MPH	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), The Emmes Company, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma concentration of NT-proBNP		Approximately 7 months
Other	Plasma concentration of MR-proANP		Approximately 7 months
Other	Right ventricular or left ventricular end diastolic volume		Approximately 7 months
Other	Right ventricular or left ventricular end systolic volume		Approximately 7 months
Other	Right ventricular or left ventricular ejection fraction		Approximately 7 months
Other	Right ventricular or left ventricular shortening fraction		Approximately 7 months
Other	Right ventricular or left ventricular end diastolic dimension		Approximately 7 months
Other	Right ventricular or left ventricular end systolic dimension		Approximately 7 months
Other	Right ventricular or left ventricular fractional area change		Approximately 7 months
Other	Degree of atrioventricular valve regurgitation		Approximately 7 months
Other	Qualitative right ventricular or left ventricular function assessment		Approximately 7 months
Other	Cardiac output	As measured by cardiac catheterization	Approximately 7 months
Other	Pulmonary to systemic blood flow ratio	As measured by cardiac catheterization	Approximately 7 months
Other	Pulmonary vascular resistance	As measured by cardiac catheterization	Approximately 7 months
Other	Mean pulmonary artery pressure	As measured by cardiac catheterization	Approximately 7 months
Other	Right ventricular or left ventricular end diastolic pressure	As measured by cardiac catheterization	Approximately 7 months
Other	Right ventricular or left ventricular end systolic pressure	As measured by cardiac catheterization	Approximately 7 months
Other	Right and left pulmonary artery size	As measured by cardiac catheterization	Approximately 7 months
Other	Pressure gradients across the aortic arch	As measured by cardiac catheterization	Approximately 7 months
Other	Incidence of unplanned surgical intervention	Including cannulation for mechanical circulatory support	Approximately 7 months
Other	Incidence of listing for heart transplant		Approximately 7 months
Other	Incidence of receiving heart transplant		Approximately 7 months
Other	Hospital length of stay after S1P		Approximately 7 months
Other	Number of days on mechanical ventilation after S1P		Approximately 7 months
Other	Number of hospital readmissions from S1P discharge to S2p		Approximately 7 months
Primary	Plasma concentrations of digoxin	The primary outcome measures are plasma concentrations of digoxin measured using a validated bioanalytical assay at a central laboratory.	Approximately 7 months
Secondary	Number of adverse events related to study procedures and serious, unexpected, suspected adverse reactions related to digoxin	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.	Approximately 7 months
Secondary	Tachyarrthmias	Event of special interest will be captured (number of tachyarrythmias)	Approximately 7 months
Secondary	Number of participants with second and third degree atrioventricular conduction block		Approximately 7 months
Secondary	Number of participants with sinus bradycardia	Number of participants with sinus bradycardia	Approximately 7 months
Secondary	Number of participants with need for temporary or permanent pacing	Number of participants with need for temporary or permanent pacing	Approximately 7 months
Secondary	Frequency of death	Frequency of death	Approximately 7 months
Secondary	PR interval	Derived from electrocardiograms and their reports performed per standard of care	Approximately 7 months
Secondary	QRS duration	Derived from electrocardiograms and their reports performed per standard of care	Approximately 7 months
Secondary	QT interval	Derived from electrocardiograms and their reports performed per standard of care	Approximately 7 months
Secondary	Corrected QT interval using Bazett's formula	Derived from electrocardiograms and their reports performed per standard of care	Approximately 7 months