Pharmacokinetics/Pharmacodynamics, Efficacy and Safety of Sacubitril/Valsartan Versus Enalapril in Pediatric Patients with Heart Failure Due to Systemic Left Ventricle Systolic Dysfunction: Study Design and Rationale

Background: Pediatric HF is characterized by significant morbidity and mortality and the rationale for medical therapy primarily comes from adult studies. Sacubitril/valsartan (LCZ696) reduced mortality and delayed HF progression vs. enalapril and was generally well tolerated in PARADIGM-HF trial in adults with HFrEF; however, benefit in pediatric patients is unknown. Study Design: This multicenter study will use an adaptive, seamless, 2-stage design (Figure). Part 1, open-label study will determine the PK/PD of single-dose LCZ696 in 36 pediatric HF patients (1 month to < 18 years) stratified into 3 age groups (Group 1:6 to < 18 years; Group 2:1 to < 6 years; Group 3:1 month to < 1 year) in a sequential overlapping fashion and in descending age-group order.

Source: Journal of Cardiac Failure - July 23, 2016 Category: Cardiology Authors: Robert Shaddy, Fabian Chen, Charles Canter, Nancy Halnon, Lazaros Kochilas, John Jefferies, Joseph Rossano, Damien Bonnet, Paul Kantor, Michael Burch Source Type: research