Pharmacokinetics and Safety Profile of Digoxin in Infants With Single Ventricle Congenital Heart Disease (DGX01)

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.

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Drug: Digoxin

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.

• Study Type: Observational
• Enrollment (Actual): 50

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Mattel Children's Hospital at UCLA
    • San Diego, California, United States, 92123
      • Rady Childrens Hospital and Health Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital Colorado
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I. DuPont Hospital for Children
  • Florida
    • Miami, Florida, United States, 33155
      • Nicklaus Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • St. Louis Children's Hospital
  • New York
    • New York, New York, United States, 10032
      • Morgan Stanley Children's Hospital of New York Presbyterian
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Cincinnati Childrens Hospital Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Children's Memorial Hermann Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 months (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Up to 48 infants diagnosed with single ventricle congenital heart disease, receiving digoxin per standard of care during the interstage period

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Children with single ventricle congenital heart disease; Receiving digoxin per standard of care during the interstage period	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Tachyarrthmias	Event of special interest will be captured (number of tachyarrythmias)	Approximately 7 months
Number of participants with second and third degree atrioventricular conduction block		Approximately 7 months
Number of participants with sinus bradycardia	Number of participants with sinus bradycardia	Approximately 7 months
Number of participants with need for temporary or permanent pacing	Number of participants with need for temporary or permanent pacing	Approximately 7 months
Frequency of death	Frequency of death	Approximately 7 months
PR interval	Derived from electrocardiograms and their reports performed per standard of care	Approximately 7 months
QRS duration	Derived from electrocardiograms and their reports performed per standard of care	Approximately 7 months
QT interval	Derived from electrocardiograms and their reports performed per standard of care	Approximately 7 months
Corrected QT interval using Bazett's formula	Derived from electrocardiograms and their reports performed per standard of care	Approximately 7 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of NT-proBNP		Approximately 7 months
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
Cardiac output	As measured by cardiac catheterization	Approximately 7 months
Pulmonary to systemic blood flow ratio	As measured by cardiac catheterization	Approximately 7 months
Pulmonary vascular resistance	As measured by cardiac catheterization	Approximately 7 months
Mean pulmonary artery pressure	As measured by cardiac catheterization	Approximately 7 months
Right ventricular or left ventricular end diastolic pressure	As measured by cardiac catheterization	Approximately 7 months
Right ventricular or left ventricular end systolic pressure	As measured by cardiac catheterization	Approximately 7 months
Right and left pulmonary artery size	As measured by cardiac catheterization	Approximately 7 months
Pressure gradients across the aortic arch	As measured by cardiac catheterization	Approximately 7 months
Incidence of unplanned surgical intervention	Including cannulation for mechanical circulatory support	Approximately 7 months
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

Collaborators and Investigators

• Sponsor: Christoph P Hornik, MD MPH
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); The Emmes Company, LLC
• Investigators: Principal Investigator: christoph Hornik, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2019
• Primary Completion (Actual): July 13, 2021
• Study Completion (Actual): January 17, 2022

Study Registration Dates

• First Submitted: March 14, 2019
• First Submitted That Met QC Criteria: March 14, 2019
• First Posted (Actual): March 18, 2019

Study Record Updates

• Last Update Posted (Actual): October 12, 2022
• Last Update Submitted That Met QC Criteria: October 10, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital; Univentricular Heart; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Digoxin
• Other Study ID Numbers: Pro00102130; NICHD-2018-DGX01 (Other Identifier: Duke); HHSN27500002 (Other Grant/Funding Number: NICHD)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No