Abstract
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, 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: The study was pre-maturely stopped due to a reported drug-drug interaction and was left under-powered. Out of 40 randomized patients 38 were included in the outcome analyses (27 IFN beta-1a and 11 placebo). There was no statistically significant difference between treatment groups at baseline. However, from surgery more open-abdomen and intestinal ischemia was present in the IFN beta-1a arm. D30 all-cause mortality was 22.2% (6/27) in the IFN beta-1a 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 IFN beta-1a arm vs. 9.1% in the placebo arm). High level of serum CD73 associated with survival (P = 0.001) whereas the use of glucocorticoids and the presence of IFN beta neutralizing antibodies associated with a poor CD73 response and survival.Conclusions: Due to the size of the study and several confounding factors a benefit from IFN beta-1a could not be determined. Survival after open RAAA surgery associated strongly with up-regulation of serum CD73. The use of glucocorticoids and IFN beta neutralizing antibodies blocked the up regulation of CD73. Trial registration: ClinicalTrials.gov NCT03119701. Registered 19/04/2017 (retrospectively registered).
Endovascular Suitability and Outcome After Open Surgery for Ruptured Abdominal Aortic Aneurysm