Induction of CD73 Prevents Death After Emergency Open Aortic Surgery for a Ruptured Abdominal Aortic Aneurysm – A Randomized, Double-Blind, Placebo-Controlled Study

Abstract

\n Background: Mortality remains high after emergency open surgery for a ruptured abdominal aortic aneurysm (RAAA). The aim of the present study was to assess, if intravenous (IV) Interferon (IFN) beta-1a improve survival after surgery by up-regulating Cluster of differentiation (CD73). Methods: This is a multi-center phase II double-blind, 2:1 randomized, parallel group comparison of the efficacy and safety of IV IFN beta-1a vs. placebo for the prevention of death after open surgery for an infra-renal RAAA. All study patients presented a confirmed infra-renal RAAA, survived the primary emergency surgery and were treated with IFN beta-1a (10μg) or matching placebo for 6 days after surgery. Major exclusion criteria included irreversible hemorrhagic shock, unconsciousness at arrival, chronic renal replacement therapy, diagnosed liver cirrhosis, severe congestive heart failure, advanced malignant disease, primary attempt of endovascular aortic repair (EVAR), and per-operative suprarenal clamping over 30 minutes. Main outcome measure was all-cause mortality at day 30 (D30) from initial emergency aortic reconstruction. Results: Out of 40 randomized patients 38 were included in the outcome analyses (27 active arm and 11 placebo). Treatment groups were comparable by baseline characteristics. D30 all-cause mortality was 22.2% (6/27) in the active arm and 18.2% (2/11) in the placebo arm (OR 1.30; 95% CI, 0.21 – 8.19). The most common adverse event relating to the IFN beta-1a was pyrexia (20.7% in the active arm vs. 9.1% in the placebo arm). High level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids associated with a poor CD73 response and poor survival in the active arm (P = 0.002).Conclusions: IV IFN beta-1a was well tolerated. Survival after open RAAA surgery associated strongly with up-regulation of serum CD73, but the use of glucocorticoids blocked IFN beta-1a from up-regulating CD73. Trial registration: ClinicalTrials.gov NCT03119701Funding/Support: This study was sponsored by Faron Pharmaceuticals Ltd.