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Harsha Shanthanna,1 Alparslan Turan,2 Jessica Vincent,3 Remie Saab,2 Yaron Shargall,4 Turlough O’Hare,1 Kimberly Davis,5 Sylvanus Fonguh,3 Kumar Balasubramaniam,3 James Paul,1 Ian Gilron,6 Henrik Kehlet,7 Daniel I Sessler,2 Mohit Bhandari,8 Lehana Thabane,9 PJ Devereaux9 1Department of Anesthesia, McMaster University, Hamilton, ON, Canada; 2Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH, USA; 3Population Health Research Institute, Hamilton, ON, Canada; 4Department of Surgery, St Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 5Acute Pain Service, St. Joseph Healthcare Hamilton, Hamilton, ON, Canada; 6Departments of Anesthesiology and Perioperative Medicine, Biomedical and Molecular Sciences, Centre for Neuroscience Studies and School of Policy Studies, Queen’s University, Kingston, ON, Canada; 7Section of Surgical Pathophysiology, Rigshospitalet, Copenhagen, Denmark; 8Department of Surgery, McMaster University, Hamilton, ON, Canada; 9Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Harsha ShanthannaDepartment of Anesthesia, McMaster University, 1280 Main St. W., Hamilton, Ontario L8S 4K1, CanadaTel +1 905-525-9140 ext. 21737Fax +1 905-523-1224Email shanthh@mcmaster.caPurpose: We conducted a feasibility 2× 2 factorial trial comparing N-methyl-D-aspartate (NMDA) antagonists (intravenous ketamine and oral memantine) versus placebo and intravenous steroids versus placebo, in patients having elective video-assisted thoracic surgery lobectomies, at St. Joseph’s Hamilton, Canada, and Cleveland Clinic, Cleveland, USA. Our feasibility objectives were: 1) recruitment rate/week; 2) recruitment of ≥ 90% of eligible patients; and 3) > 90% follow-up. Secondary objectives were incidence and intensity of persistent post-surgical pain (PPSP) and other clinical and safety outcomes.Methods: Using computerized randomization, patients were allocated to one of four groups: NMDA active with steroid placebo; NMDA placebo with steroid active; both NMDA and steroid active; both NMDA and steroid placebo. Patients, health providers, and data analysts were blinded to allocation. Patients were followed for 3 months after randomization.Results: The trial was initiated in May 2017 at Hamilton and, after subsequent regulatory and ethics approval, in April 2018 at Cleveland. The trial had to be stopped after only 1 month of recruitment in Cleveland because the packaged study medications (memantine) expired and we were unable to procure the dosage required. Among 41 eligible patients, 27 (66%) were randomized. The recruitment rate/week was 0.63, 95% confidence interval (CI): 0.47– 0.79 in Hamilton; and 1, 95% CI: 0.83– 1.17 in Cleveland. Follow-up was complete for all 24 patients (100%) in Hamilton, and 3 of 4 patients in Cleveland. In total, only 4 patients (15%), and 2 patients (7%) had persistent pain at rest and with movement, respectively. There were no significant differences between groups for other outcomes.Conclusion: The trial had to be stopped prematurely due to non-availability of study medications. Trial feasibility objectives of recruiting 90% of eligible patients and recruiting at least one patient/week per site were not met. Consideration for protocol changes will be necessary for the full trial.Trial Registration: NCT02950233.Keywords: persisting pain, chronic pain, prevention, NMDA antagonists, steroids, ketamine