Methadone to Reduce Chronic Opioid Use After Major Spine Surgery: The MEND Pilot Feasibility Study

Feasibility and Acceptability-Participant Willingness/Recruitment

Willingness of participants to be randomized Indicates acceptability of randomization among eligible patients Outcome Measure: % of eligible patient consenting to randomization

Feasibility and Acceptability-Provider Engagement

Feasibility, acceptability and execution of clinical protocol based on the use of intraoperative IV methadone followed by a postoperative oral methadone regimen following spine surgery will be assessed by yes/no response to the following: Willingness of neurosurgeons/anesthesiologists to buy in to the trial Reflects institutional buy-in and clinical integration potential Outcome Measure: % of surgeons permitting patient enrollment and supporting protocol adherence

Feasibility and Execution-Protocol Compliance and Execution

Feasibility of clinical protocol based on the use of intraoperative IV methadone followed by a postoperative oral methadone regimen following spine surgery will be assessed by yes/no response to the following: Compliance with the protocol, including specific study related procedures and timepoints specific to medication administration, adverse event reporting and data collection. Demonstrates deliverability and data reliability Outcome Measure: % adherence to all major protocol steps (drug administration, ECGs, AE reporting, opioid data)

Acceptability and Execution-Baseline Stratification Data

Outcome Measure: % of enrolled patients with prior chronic opioid use

Execution-Collection of Cardiac Rhythm Abnormalities

1\) ECG collected on postoperative days 1, 2 and 3. Presence of cardiac arrhythmias (frequent premature ventricular contractions, ventricular arrhythmias) requiring treatment will be collected. An increase in QTc interval \>500 ms or \>25% from baseline will be compared to baseline ECG,

Execution-Collection of Respiratory Adverse Events

Respiratory depression indicators will be measured every 6 hours. 1\) The presence of any of the following will be considered respiratory depression: 1. Respiratory rate \<8 or oxygen saturation \<90% for longer than 5 minutes 2. Increased oxygen requirement by ≥ 2 L O2 for 15 min 3. naloxone use. Patients who are receiving 4. supplemental oxygen

Estimate Reduction in Opioid Use

To estimate reduction in opioid use (Morphine Milligram Equivalents, MME) in the acute postoperative period as a mechanistic indicator for decrease in opioid usage at 3 months. Postoperative 5-day opioid requirements assessed by total MME (5 days duration or length of hospitalization, whichever is earlier) will be compared between methadone and placebo groups

Development of and effective study design

To estimate key design parameters (variability and effect size) of a large clinical trial which will evaluate the reduction in chronic opioid use at 3 months post-surgery. Focusing on estimating parameters that will be needed to appropriately calculate the sample size for a larger trial.