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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

Tracking Information
First Submitted Date March 14, 2019
First Posted Date March 18, 2019
Last Update Posted Date March 12, 2021
Actual Study Start Date August 5, 2019
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 10, 2021)
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.
Original Primary Outcome Measures
 (submitted: March 14, 2019)
Plasma concentrations of dixogin [ Time Frame: Approximately 7 months ]
Change History
Current Secondary Outcome Measures
 (submitted: March 10, 2021)
  • 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.
  • Tachyarrthmias [ Time Frame: Approximately 7 months ]
    Event of special interest will be captured (number of tachyarrythmias)
  • Number of participants with second and third degree atrioventricular conduction block [ Time Frame: Approximately 7 months ]
  • Number of participants with sinus bradycardia [ Time Frame: Approximately 7 months ]
    Number of participants with sinus bradycardia
  • 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
  • Frequency of death [ Time Frame: Approximately 7 months ]
    Frequency of death
  • PR interval [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care
  • QRS duration [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care
  • QT interval [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care
  • Corrected QT interval using Bazett's formula [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care
Original Secondary Outcome Measures
 (submitted: March 14, 2019)
  • Adverse events related to study procedures and serious, unexpected, suspected adverse reactions related to digoxin [ Time Frame: Approximately 7 months ]
  • Tachyarrythmias [ Time Frame: Approximately 7 months ]
  • Second and third degree atrioventricular conduction block [ Time Frame: Approximately 7 months ]
  • Sinus bradycardia [ Time Frame: Approximately 7 months ]
  • Need for temporary or permanent pacing [ Time Frame: Approximately 7 months ]
  • Death [ Time Frame: Approximately 7 months ]
  • PR interval [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care
  • QRS duration [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care
  • QT interval [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care
  • Corrected QT interval using Bazett's formula [ Time Frame: Approximately 7 months ]
    Derived from electrocardiograms and their reports performed per standard of care
Current Other Pre-specified Outcome Measures
 (submitted: March 14, 2019)
  • Plasma concentration of NT-proBNP [ Time Frame: Approximately 7 months ]
  • Plasma concentration of MR-proANP [ Time Frame: Approximately 7 months ]
  • Right ventricular or left ventricular end diastolic volume [ Time Frame: Approximately 7 months ]
  • Right ventricular or left ventricular end systolic volume [ Time Frame: Approximately 7 months ]
  • Right ventricular or left ventricular ejection fraction [ Time Frame: Approximately 7 months ]
  • Right ventricular or left ventricular shortening fraction [ Time Frame: Approximately 7 months ]
  • Right ventricular or left ventricular end diastolic dimension [ Time Frame: Approximately 7 months ]
  • Right ventricular or left ventricular end systolic dimension [ Time Frame: Approximately 7 months ]
  • Right ventricular or left ventricular fractional area change [ Time Frame: Approximately 7 months ]
  • Degree of atrioventricular valve regurgitation [ Time Frame: Approximately 7 months ]
  • Qualitative right ventricular or left ventricular function assessment [ Time Frame: Approximately 7 months ]
  • Cardiac output [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
  • Pulmonary to systemic blood flow ratio [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
  • Pulmonary vascular resistance [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
  • Mean pulmonary artery pressure [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
  • Right ventricular or left ventricular end diastolic pressure [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
  • Right ventricular or left ventricular end systolic pressure [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
  • Right and left pulmonary artery size [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
  • Pressure gradients across the aortic arch [ Time Frame: Approximately 7 months ]
    As measured by cardiac catheterization
  • Incidence of unplanned surgical intervention [ Time Frame: Approximately 7 months ]
    Including cannulation for mechanical circulatory support
  • Incidence of listing for heart transplant [ Time Frame: Approximately 7 months ]
  • Incidence of receiving heart transplant [ Time Frame: Approximately 7 months ]
  • Hospital length of stay after S1P [ Time Frame: Approximately 7 months ]
  • Number of days on mechanical ventilation after S1P [ Time Frame: Approximately 7 months ]
  • Number of hospital readmissions from S1P discharge to S2p [ Time Frame: Approximately 7 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Pharmacokinetics and Safety Profile of Digoxin in Infants With Single Ventricle Congenital Heart Disease
Official Title Pharmacokinetics and Safety Profile of Digoxin in Infants With Single Ventricle Congenital Heart Disease
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.
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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Blood samples will be collected to assess pharmacokinetic and biomarker levels
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
Condition Congenital Heart Disease
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
Study Groups/Cohorts Children with single ventricle congenital heart disease
Receiving digoxin per standard of care during the interstage period
Intervention: Drug: Digoxin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Enrolling by invitation
Estimated Enrollment
 (submitted: March 14, 2019)
48
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 1, 2022
Estimated Primary Completion Date July 1, 2022   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages up to 6 Months   (Child)
Accepts Healthy Volunteers Not Provided
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03877965
Other Study ID Numbers Pro00102130
NICHD-2018-DGX01 ( Other Identifier: Duke )
HHSN27500002 ( Other Grant/Funding Number: NICHD )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Christoph P Hornik, MD MPH, Duke University
Study 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
PRS Account Duke University
Verification Date March 2021