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

• ClinicalTrials.gov Identifier: NCT03877965
• Recruitment Status: Enrolling by invitation
• First Posted: March 18, 2019
• Last Update Posted: October 1, 2020
• Sponsor: Christoph P Hornik, MD MPH
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); The Emmes Company, LLC
• Information provided by (Responsible Party): Christoph P Hornik, MD MPH, Duke University

Study Description

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.

Condition or disease	Intervention/treatment
Congenital Heart Disease	Drug: Digoxin

Study Design

• Study Type: Observational
• Estimated Enrollment: 48 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Pharmacokinetics and Safety Profile of Digoxin in Infants With Single Ventricle Congenital Heart Disease
• Actual Study Start Date: August 5, 2019
• Estimated Primary Completion Date: July 1, 2022
• Estimated Study Completion Date: December 1, 2022

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

1. Plasma concentrations of digoxin [ Time Frame: Approximately 7 months ]

Secondary Outcome Measures :

1. Number of adverse events related to study procedures and serious, unexpected, suspected adverse reactions related to digoxin [ Time Frame: Approximately 7 months ]
2. Number of participants with tachyarrhythmias [ Time Frame: Approximately 7 months ]
3. Number of participants with second and third degree atrioventricular conduction block [ Time Frame: Approximately 7 months ]
4. Number of participants with sinus bradycardia [ Time Frame: Approximately 7 months ]
5. Number of participants with need for temporary or permanent pacing [ Time Frame: Approximately 7 months ]
6. Frequency of death [ Time Frame: Approximately 7 months ]
7. PR interval [ Time Frame: Approximately 7 months ]
   Derived from electrocardiograms and their reports performed per standard of care
8. QRS duration [ Time Frame: Approximately 7 months ]
   Derived from electrocardiograms and their reports performed per standard of care
9. QT interval [ Time Frame: Approximately 7 months ]
   Derived from electrocardiograms and their reports performed per standard of care
10. Corrected QT interval using Bazett's formula [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care

Other Outcome Measures:

1. Plasma concentration of NT-proBNP [ Time Frame: Approximately 7 months ]
2. Plasma concentration of MR-proANP [ Time Frame: Approximately 7 months ]
3. Right ventricular or left ventricular end diastolic volume [ Time Frame: Approximately 7 months ]
4. Right ventricular or left ventricular end systolic volume [ Time Frame: Approximately 7 months ]
5. Right ventricular or left ventricular ejection fraction [ Time Frame: Approximately 7 months ]
6. Right ventricular or left ventricular shortening fraction [ Time Frame: Approximately 7 months ]
7. Right ventricular or left ventricular end diastolic dimension [ Time Frame: Approximately 7 months ]
8. Right ventricular or left ventricular end systolic dimension [ Time Frame: Approximately 7 months ]
9. Right ventricular or left ventricular fractional area change [ Time Frame: Approximately 7 months ]
10. Degree of atrioventricular valve regurgitation [ Time Frame: Approximately 7 months ]
11. Qualitative right ventricular or left ventricular function assessment [ Time Frame: Approximately 7 months ]
12. Cardiac output [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
13. Pulmonary to systemic blood flow ratio [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
14. Pulmonary vascular resistance [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
15. Mean pulmonary artery pressure [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
16. Right ventricular or left ventricular end diastolic pressure [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
17. Right ventricular or left ventricular end systolic pressure [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
18. Right and left pulmonary artery size [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
19. Pressure gradients across the aortic arch [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
20. Incidence of unplanned surgical intervention [ Time Frame: Approximately 7 months ]
    Including cannulation for mechanical circulatory support
21. Incidence of listing for heart transplant [ Time Frame: Approximately 7 months ]
22. Incidence of receiving heart transplant [ Time Frame: Approximately 7 months ]
23. Hospital length of stay after S1P [ Time Frame: Approximately 7 months ]
24. Number of days on mechanical ventilation after S1P [ Time Frame: Approximately 7 months ]
25. Number of hospital readmissions from S1P discharge to S2p [ Time Frame: Approximately 7 months ]

Biospecimen Retention:   Samples Without DNA

Blood samples will be collected to assess pharmacokinetic and biomarker levels

Eligibility Criteria

• Ages Eligible for Study: up to 6 Months (Child)
• Sexes 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

Criteria

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

Contacts and Locations

Locations

United States, California

Mattel Children's Hospital at UCLA

Los Angeles, California, United States, 90095

Rady Childrens Hospital and Health Center

San Diego, California, United States, 92123

United States, Colorado

The Children's Hospital Colorado

Aurora, Colorado, United States, 80045

United States, Delaware

Alfred I. DuPont Hospital for Children

Wilmington, Delaware, United States, 19803

United States, Florida

Nicklaus Children's Hospital

Miami, Florida, United States, 33155

United States, Missouri

St. Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

United States, New York

Morgan Stanley Children's Hospital of New York Presbyterian

New York, New York, United States, 10032

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Cincinnati Childrens Hospital Medical Center

Cincinnati, Ohio, United States, 45229-3039

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

United States, Texas

Children's Memorial Hermann Hospital

Houston, Texas, United States, 77030

Sponsors and Collaborators

Christoph P Hornik, MD MPH

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

The Emmes Company, LLC

Investigators

• Principal Investigator: Christoph Hornik, MD; Duke University

More Information

• Responsible Party: Christoph P Hornik, MD MPH, Associate Professor of Pediatrics, Duke University
• ClinicalTrials.gov Identifier: NCT03877965
• Other Study ID Numbers: Pro00102130; NICHD-2018-DGX01 ( Other Identifier: Duke ); HHSN27500002 ( Other Grant/Funding Number: NICHD )
• First Posted: March 18, 2019
• Last Update Posted: October 1, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Heart Diseases; Heart Defects, Congenital; Cardiovascular Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Digoxin; Anti-Arrhythmia Agents; Cardiotonic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs