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

Sponsor
Christoph P Hornik, MD MPH (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT03877965
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), The Emmes Company, LLC (Industry)
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Study Details

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 Phase

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 Design

Study Type:
Observational
Actual Enrollment :
50 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 :
Aug 5, 2019
Anticipated Primary Completion Date :
Jul 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm 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 [Approximately 7 months]

    The primary outcome measures are plasma concentrations of digoxin measured using a validated bioanalytical assay at a central laboratory.

Secondary Outcome Measures

  1. 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.

  2. Tachyarrthmias [Approximately 7 months]

    Event of special interest will be captured (number of tachyarrythmias)

  3. Number of participants with second and third degree atrioventricular conduction block [Approximately 7 months]

  4. Number of participants with sinus bradycardia [Approximately 7 months]

    Number of participants with sinus bradycardia

  5. Number of participants with need for temporary or permanent pacing [Approximately 7 months]

    Number of participants with need for temporary or permanent pacing

  6. Frequency of death [Approximately 7 months]

    Frequency of death

  7. PR interval [Approximately 7 months]

    Derived from electrocardiograms and their reports performed per standard of care

  8. QRS duration [Approximately 7 months]

    Derived from electrocardiograms and their reports performed per standard of care

  9. QT interval [Approximately 7 months]

    Derived from electrocardiograms and their reports performed per standard of care

  10. Corrected QT interval using Bazett's formula [Approximately 7 months]

    Derived from electrocardiograms and their reports performed per standard of care

Other Outcome Measures

  1. Plasma concentration of NT-proBNP [Approximately 7 months]

  2. Plasma concentration of MR-proANP [Approximately 7 months]

  3. Right ventricular or left ventricular end diastolic volume [Approximately 7 months]

  4. Right ventricular or left ventricular end systolic volume [Approximately 7 months]

  5. Right ventricular or left ventricular ejection fraction [Approximately 7 months]

  6. Right ventricular or left ventricular shortening fraction [Approximately 7 months]

  7. Right ventricular or left ventricular end diastolic dimension [Approximately 7 months]

  8. Right ventricular or left ventricular end systolic dimension [Approximately 7 months]

  9. Right ventricular or left ventricular fractional area change [Approximately 7 months]

  10. Degree of atrioventricular valve regurgitation [Approximately 7 months]

  11. Qualitative right ventricular or left ventricular function assessment [Approximately 7 months]

  12. Cardiac output [Approximately 7 months]

    As measured by cardiac catheterization

  13. Pulmonary to systemic blood flow ratio [Approximately 7 months]

    As measured by cardiac catheterization

  14. Pulmonary vascular resistance [Approximately 7 months]

    As measured by cardiac catheterization

  15. Mean pulmonary artery pressure [Approximately 7 months]

    As measured by cardiac catheterization

  16. Right ventricular or left ventricular end diastolic pressure [Approximately 7 months]

    As measured by cardiac catheterization

  17. Right ventricular or left ventricular end systolic pressure [Approximately 7 months]

    As measured by cardiac catheterization

  18. Right and left pulmonary artery size [Approximately 7 months]

    As measured by cardiac catheterization

  19. Pressure gradients across the aortic arch [Approximately 7 months]

    As measured by cardiac catheterization

  20. Incidence of unplanned surgical intervention [Approximately 7 months]

    Including cannulation for mechanical circulatory support

  21. Incidence of listing for heart transplant [Approximately 7 months]

  22. Incidence of receiving heart transplant [Approximately 7 months]

  23. Hospital length of stay after S1P [Approximately 7 months]

  24. Number of days on mechanical ventilation after S1P [Approximately 7 months]

  25. Number of hospital readmissions from S1P discharge to S2p [Approximately 7 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
N/A to 6 Months
Sexes Eligible for Study:
All
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

Site City State Country Postal Code
1 Mattel Children's Hospital at UCLA Los Angeles California United States 90095
2 Rady Childrens Hospital and Health Center San Diego California United States 92123
3 The Children's Hospital Colorado Aurora Colorado United States 80045
4 Alfred I. DuPont Hospital for Children Wilmington Delaware United States 19803
5 Nicklaus Children's Hospital Miami Florida United States 33155
6 St. Louis Children's Hospital Saint Louis Missouri United States 63110
7 Morgan Stanley Children's Hospital of New York Presbyterian New York New York United States 10032
8 Duke University Medical Center Durham North Carolina United States 27710
9 Cincinnati Childrens Hospital Medical Center Cincinnati Ohio United States 45229-3039
10 Medical University of South Carolina Charleston South Carolina United States 29425
11 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
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
  • HHSN27500002
First Posted:
Mar 18, 2019
Last Update Posted:
Jul 21, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
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:

Study Results

No Results Posted as of Jul 21, 2021