Protocol Deviation in Pharmacokinetics and Safety Profile of Digoxin in Infants with Single-Ventricle Congenital Heart Disease

Protocol Deviation Information
Study Description
This study was a prospective, multi-center, open-label, pharmacokinetic (PK) and safety profile study. The study was designed to gather population-specific PK data to identify the optimal dose in a population of infants with single-ventricle (SV) congenital heart disease (CHD) and to obtain the safety profile of digoxin in infants age ≤ 30 days of life at time of stage 1 palliation. PK analysis was primarily performed using population PK methodologies. Simulations suggested that to maximize the proportion of infants with SV CHD achieving a minimum concentration on steady state between 0.5 and 2 ng/mL, as recommended in the current digoxin package insert, doses should be optimized based on weight, estimated glomerular filtration rate, and postnatal age. Two fatal serious adverse events (both resulting from hypoplastic left heart syndrome) were reported, but they were not related to study drug. Based on these data, digoxin appears safe in infants with SV CHD. The study population (N=50) was comprised of infants with single-ventricle congenital heart disease status post-surgical or hybrid stage 1 palliation but prior to surgical stage 2 palliation.