N-Methyl-D-Aspartate Antagonists and Steroids for the Prevention of Persisting Post-Surgical Pain After Thoracoscopic Surgeries: A Randomized Controlled, Factorial Design, International, Multicenter Pilot Trial.

PURPOSE: 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.