Robert Shaddy1, Charles Canter2, Nancy Halnon3, Lazaros Kochilas4, Joseph Rossano5, Damien Bonnet6, Christopher Bush7, Ziqiang Zhao8, Paul Kantor9, Michael Burch10, Fabian Chen11. 1. Children's Hospital Los Angeles, Los Angeles, CA. Electronic address: rshaddy@chla.usc.edu. 2. Washington University, St Louis, MO. 3. University of California Los Angeles, Los Angeles, CA. 4. Children's Health Care of Atlanta, Atlanta, GA. 5. The Children's Hospital of Philadelphia, Philadelphia, PA. 6. Necker Hospital University, Paris, France. 7. Novartis Pharmaceuticals Corporation, East Hanover, NJ. 8. Novartis Pharmaceuticals Corporation, Shanghai, China. 9. University of Alberta, Edmonton, Canada. 10. Great Ormond Street Hospital for Children, London, UK. 11. Novartis Pharmaceuticals Corporation, Shanghai, China. Electronic address: fabian.chen@novartis.com.
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 reducedleft 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.
RCT Entities:
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 HFpatients 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 HFpatients with reduced systemic left ventricular systolic function.
Authors: Syed Awais Attique; Muhammad Hassan; Muhammad Usman; Rana Muhammad Atif; Shahid Mahboob; Khalid A Al-Ghanim; Muhammad Bilal; Muhammad Zohaib Nawaz Journal: Int J Environ Res Public Health Date: 2019-03-14 Impact factor: 3.390
Authors: Hugo R Martinez; Gary S Beasley; Jason F Goldberg; Mohammed Absi; Kaitlin A Ryan; Karine Guerrier; Vijaya M Joshi; Jason N Johnson; Cara E Morin; Caitlin Hurley; Ronald Ray Morrison; Parul Rai; Jane S Hankins; Michael W Bishop; Brandon M Triplett; Matthew J Ehrhardt; Ching-Hon Pui; Hiroto Inaba; Jeffrey A Towbin Journal: Children (Basel) Date: 2021-12-18