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Trial record 1 of 1 for:    NCT03877965
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Pharmacokinetics and Safety Profile of Digoxin in Infants With Single Ventricle Congenital Heart Disease (DGX01)

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ClinicalTrials.gov Identifier: NCT03877965
Recruitment Status : Enrolling by invitation
First Posted : March 18, 2019
Last Update Posted : March 12, 2021
Sponsor:
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

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

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.

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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

Resource links provided by the National Library of Medicine

Drug Information available for: Digoxin

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




Primary Outcome Measures :
  1. Plasma concentrations of digoxin [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Approximately 7 months ]
  4. Number of participants with sinus bradycardia [ Time Frame: Approximately 7 months ]
    Number of participants with sinus bradycardia

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

  6. Frequency of death [ Time Frame: Approximately 7 months ]
    Frequency of death

  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


Information from the National Library of Medicine

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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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03877965


Locations
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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
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Principal Investigator: Christoph Hornik, MD Duke University
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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    Key Record Dates
Last Update Posted: March 12, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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