R. Shaddy, C. Canter, N. Halnon
Nov 1, 2017
Citations
2
Influential Citations
54
Citations
Quality indicators
Journal
American Heart Journal
Abstract
Background Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. Study design This global multi‐center study will use an adaptive, seamless two‐part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52‐week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst‐to‐best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient‐reported HF symptoms will be used to assess efficacy. Conclusion The PANORAMA‐HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function. Graphical abstract Design of the two‐stage, seamless, adaptive PANORAMA‐HF study assessing the PK/PD, safety, and efficacy of sacubitril/valsartan versus enalapril in pediatric heart failure patients with systemic left ventricle and reduced left ventricular systolic function. Figure. No Caption available.