Randomized, Placebo-Controlled Trial of Peri-Operative Treprostinil in Pediatric Patients Undergoing the Fontan Operation.

Abstract

The objective of this study is to assess the effect of subcutaneous treprostinil (TRE) administered peri-operatively after Fontan operation on chest tube duration (CTD), hospital length of stay (LOS), and post-operative hemodynamics. This is a single center randomized, blinded, placebo-controlled study of pediatric patients with single ventricle congenital heart disease undergoing Fontan operation between September 2015 and September 2019. Patients were randomized to receive subcutaneous TRE (target dose 10 ng/kg/min) or saline placebo starting intraoperatively through post-operative day 7. Baseline demographics, pre-operative hemodynamics, and peri-operative clinical details were collected. The primary outcome was CTD. Secondary outcomes included hospital LOS and hemodynamics. Thirty-four patients were randomized, 16 to TRE and 18 to saline placebo. Baseline characteristics were similar between groups, including pre-operative hemodynamics. Patients receiving TRE had increased risk for longer CTD (median CTD 8 vs. 7 days compared to placebo [IQR: 7-12.5, 5-8 days, respectively] with a relative risk (RR) of 1.29 (95% CI: 1.02, 1.64; p = 0.03)) and increased risk for longer hospital LOS (median LOS 11 vs. 9 days compared to placebo [IQR: 9.5-14.5, 8-10 days, respectively] with a RR of 1.23 (95% CI: 1.00, 1.51; p = 0.05)). Patients receiving TRE had higher median Fontan pressure at post-operative hour 12 (13 mmHg [IQR: 12.5-15.0] vs. 10.5 mmHg [IQR: 8.0-12.5]; p < 0.01 on repeated measure analysis model) and greater transpulmonary gradient at post-operative hour 12 (7.0 mmHg [IQR: 5.0-9.5] vs. 4.0 mmHg [IQR: 3.5-5.0]; p < 0.01 on repeated measure analysis model) compared to placebo. Peri-operative subcutaneous TRE did not reduce CTD or hospital LOS after Fontan operation and did not exert significant beneficial effects on post-operative hemodynamics. Accordingly, TRE at a dose of 10 ng/kg/min is not recommended for routine use in immediate post-operative Fontan management.