Intravenous Sildenafil in the Treatment of Neonates with Persistent Pulmonary Hypertension
Received 3 February 2009; received in revised form 8 May 2009; accepted 8 June 2009. published online 16 October 2009.
Objective
To evaluate the safety of intravenous (IV) sildenafil, an inhibitor of cyclic guanosine monophosphate–specific phosphodiesterase, in treating near-term and term newborns with persistent pulmonary hypertension of the newborn (PPHN).
Study design
This was an open-label, dose-escalation trial in newborns with PPHN and an oxygenation index (OI) > 15. Sildenafil was delivered by continuous IV infusion for at least 48 hours and up to 7 days.
Results
Five centers enrolled a total of 36 neonates with PPHN at a mean of 34 ± 17 hours of age; 29 of these neonates were already receiving inhaled nitric oxide (iNO). A significant improvement in OI (28.7 to 19.3; P = .0002) was observed after 4 hours of sildenafil infusion in the higher dose cohorts. Thirty-five neonates survived; 1 neonate required extracorporeal membrane oxygenation (ECMO) support. In 4 neonates, sildenafil was stopped due to adverse events. Seven neonates were enrolled before developing the need for iNO. In these neonates, OI improved significantly by 4 hours after initiation of sildenafil infusion (24.6 to 14.7; P = .009); 6 neonates completed treatment without the need for iNO or ECMO.
Conclusions
IV sildenafil was well tolerated, and acute and sustained improvements in oxygenation were noted in those neonates who received the higher infusion doses.
aDepartment of Pediatrics, Northwestern University Feinberg School of Medicine and Children's Memorial Hospital, Chicago, IL
bDepartment of Pediatrics, University of Colorado and The Children's Hospital, Denver, CO
cPaediatric and Neonatal Intensive Care Unit, Great Ormond Street Hospital for Children, London, UK
dDivision of Cardiopulmonary Sciences, University of Kent, Canterbury, UK
ePfizer Global Research and Development, Sandwich, UK
fDepartment of Pediatrics, Children's National Medical Center, Washington, DC
Reprint requests: Robin H. Steinhorn, MD, Children's Memorial Hospital, 2300 Children's Plaza, Box 45, Chicago, IL 60614.
The study sponsor (Pfizer) provided the intravenous sildenafil, financial support for the clinical research nurse and other costs of conducting the study at each site, as well as ongoing site monitoring. The data analysis was performed by the academic authors and reviewed by statisticians who are employees of Pfizer (M.D. and M.O.). The manuscript was prepared by R.H.S., G.B., and J.P.K. No honorarium or other payment was provided to produce the manuscript.
ABSTRACT