Adenosine A2A receptor agonist (regadenoson) in Human Lung Transplantation

Christine L. Lau, Jared P. Beller, Joshua A. Boys, Yunge Zhao, Jennifer Phillips, Michael Cosner, Mark R. Conaway, Gina Petroni, Eric J. Charles, J. H. Mehaffey, Hannah C. Mannem, Irving L. Kron, Alexander S. Krupnick, Joel Linden

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Currently, there are no clinically approved treatments for ischemia-reperfusion injury after lung transplantation. Pre-clinical animal models have demonstrated a promising efficacy of adenosine 2A receptor (A2AR) agonists as a treatment option for reducing ischemia-reperfusion injury. The purpose of this human study, is to conduct a Phase I clinical trial for evaluating the safety of continuous infusion of an A2AR agonist in lung transplant recipients. METHODS: An adaptive, two-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 that was started at the time of skin incision. Adverse events and dose-limiting toxicities, as pre-determined by a study team and assessed by a clinical team and an independent safety monitor, were the primary end-points 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 1.44 µg/kg/min for 12 hours. No dose-limiting toxicities were observed. The steady-state plasma regadenoson levels sampled before the reperfusion of the first lung were 0.98 ± 0.46 ng/ml. There were no mortalities within 30 days. CONCLUSIONS: 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 the evaluation of secondary end-points, the results of this trial and the outcome of pre-clinical studies warrant further investigation with a Phase II randomized controlled trial.

Original languageEnglish (US)
Pages (from-to)563-570
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume39
Issue number6
DOIs
StatePublished - Jun 2020

Keywords

  • IRI
  • adenosine
  • clinical trial
  • end stage lung disease
  • lung transplant
  • pulmonary fibrosis
  • transplantation

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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    Lau, C. L., Beller, J. P., Boys, J. A., Zhao, Y., Phillips, J., Cosner, M., Conaway, M. R., Petroni, G., Charles, E. J., Mehaffey, J. H., Mannem, H. C., Kron, I. L., Krupnick, A. S., & Linden, J. (2020). Adenosine A2A receptor agonist (regadenoson) in Human Lung Transplantation. Journal of Heart and Lung Transplantation, 39(6), 563-570. https://doi.org/10.1016/j.healun.2020.02.003