FIRST IN HUMAN LUNG TRANSPLANTATION: ADENOSINE A2A RECEPTOR AGONIST (REGADENOSON)

Abstract Background: Currently, no clinically available treatment exists for ischemia-reperfusion injury (IRI) following lung transplantation. Pre-clinical animal models have shown adenosine 2A receptor (A2AR) agonists are effective treatment options for reducing IRI. The purpose of this first in human study was to conduct a Phase I clinical trial to evaluate the safety of continuous infusion of an A2AR agonist in lung transplant recipients. Methods: An adaptive, 2-stage continual reassessment trial was designed to evaluate the safety of regadenoson (A2AR agonist) in the setting of lung transplantation. Continuous infusion of regadenoson was administered to lung transplant recipients beginning at the time of skin incision. Adverse events and dose limiting toxicities, as predetermined by a study team and assessed by a clinical team and an independent safety monitor, were the primary endpoints for safety in this trial. Results: Between January 2018 and March 2019, 14 recipients were enrolled in the trial. Of these, 10 received the maximum infused dose of 1.44ug/kg/min for 12 hours. No dose limiting toxicities were observed. Steady state plasma regadenoson levels sampled prior to reperfusion of the first lung were 0.98 ± 0.46 ng/ml. There were no mortalities within 30 days. Conclusion: Regadenoson, an A2AR agonist, can be safely infused in the setting of lung transplantation with no dose limiting toxicities or drug related mortality. Although not powered for evaluation of secondary endpoints, the results of this trial and the outcome of preclinical studies warrant further investigation with a Phase II randomized controlled trial.