Clinical trial NCT03877965: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Heart Disease
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: The Emmes Company, LLC
First posted: 2019-03-18
Enrollment: 50
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

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

Primary outcomes:
measure: Plasma concentrations of digoxin
timeFrame: Approximately 7 months
Secondary outcomes:
measure: Number of adverse events related to study procedures and serious, unexpected, suspected adverse reactions related to digoxin
timeFrame: Approximately 7 months
measure: Tachyarrthmias
timeFrame: Approximately 7 months
measure: Number of participants with second and third degree atrioventricular conduction block
timeFrame: Approximately 7 months
measure: Number of participants with sinus bradycardia
timeFrame: Approximately 7 months
measure: Number of participants with need for temporary or permanent pacing
timeFrame: Approximately 7 months
measure: Frequency of death
timeFrame: Approximately 7 months
measure: PR interval
timeFrame: Approximately 7 months
measure: QRS duration
timeFrame: Approximately 7 months
measure: QT interval
timeFrame: Approximately 7 months
measure: Corrected QT interval using Bazett's formula
timeFrame: Approximately 7 months
Other outcomes:
measure: Plasma concentration of NT-proBNP
timeFrame: Approximately 7 months
measure: Plasma concentration of MR-proANP
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular end diastolic volume
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular end systolic volume
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular ejection fraction
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular shortening fraction
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular end diastolic dimension
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular end systolic dimension
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular fractional area change
timeFrame: Approximately 7 months
measure: Degree of atrioventricular valve regurgitation
timeFrame: Approximately 7 months
measure: Qualitative right ventricular or left ventricular function assessment
timeFrame: Approximately 7 months
measure: Cardiac output
timeFrame: Approximately 7 months
measure: Pulmonary to systemic blood flow ratio
timeFrame: Approximately 7 months
measure: Pulmonary vascular resistance
timeFrame: Approximately 7 months
measure: Mean pulmonary artery pressure
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular end diastolic pressure
timeFrame: Approximately 7 months
measure: Right ventricular or left ventricular end systolic pressure
timeFrame: Approximately 7 months
measure: Right and left pulmonary artery size
timeFrame: Approximately 7 months
measure: Pressure gradients across the aortic arch
timeFrame: Approximately 7 months
measure: Incidence of unplanned surgical intervention
timeFrame: Approximately 7 months
measure: Incidence of listing for heart transplant
timeFrame: Approximately 7 months
measure: Incidence of receiving heart transplant
timeFrame: Approximately 7 months
measure: Hospital length of stay after S1P
timeFrame: Approximately 7 months
measure: Number of days on mechanical ventilation after S1P
timeFrame: Approximately 7 months
measure: Number of hospital readmissions from S1P discharge to S2p
timeFrame: Approximately 7 months
Locations:
city: Los Angeles
country: United States
facility: Mattel Children's Hospital at UCLA
state: California
city: San Diego
country: United States
facility: Rady Childrens Hospital and Health Center
state: California
city: Aurora
country: United States
facility: The Children's Hospital Colorado
state: Colorado
city: Wilmington
country: United States
facility: Alfred I. DuPont Hospital for Children
state: Delaware
city: Miami
country: United States
facility: Nicklaus Children's Hospital
state: Florida
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York Presbyterian
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Children's Memorial Hermann Hospital
state: Texas
Study officials:
affiliation: Duke University
name: Christoph Hornik, MD
role: PRINCIPAL_INVESTIGATOR
References: