Clinical Effectiveness of Pre-operative Methadone in Single Level Lateral Transpsoas Interbody Fusions

Clinical Effectiveness of Pre-operative Methadone in Single Level Lateral Transpsoas Interbody Fusions: A Randomized, Double-blinded, Controlled Trial

Spinal operations including lumbar fusions for degenerative disorders are becoming more prevalent as the population ages. Inadequate or excessive postoperative analgesia can result in medical comorbidities and prolonged hospital length of stay and patient dissatisfaction.

Existing literature has highlighted the preoperative administration of methadone as a promising adjuvant for post operative pain control. Methadone has the benefit of being long-acting and has more stable serum concentration and a single preoperative dose may have significant benefits post operatively.

Here the investigators propose a prospective parallel-group, randomized, double-blinded study to assess post operative analgesic requirements after preoperative administration of either methadone 15 mg or Oxycodone 10/325. Primary outcome will be total IV and PO narcotic consumption in the post operative course. Secondary outcomes examined will include time to mobility, need for specialist pain management consultation, early readmission (within 2 weeks) for inadequate pain control, and complications associated with administration.

Study Overview

• Status: Unknown
• Conditions: Degenerative Disc Disease; Spondylolisthesis, Lumbar Region
• Intervention / Treatment: Drug: Methadone Hydrochloride; Drug: Oxycodone-Acetaminophen

Detailed Description

Lumbar spinal fusions are becoming increasingly popular and prevalent in the treatment of a variety of spinal pathologies, but predominantly for degenerative disease which is most prevalent in the obese and or older population. These operations can result in relatively high post operative surgical pain and necessitate significant post operative opioid consumption which can precipitate co-morbid medical conditions such as respiratory depression and failure, pneumonia, gastrointestinal ileus, deep venous thrombosis, and pulmonary embolism. Additionally, these medical comorbidities also represent an increased burden on healthcare expenditure with increased length of hospital stay, inpatient testing and treatment, and need for additional follow up.

The investigators objective is to study the effect of a long term opioid analgesic, methadone, in a uniform population undergoing a single level minimally invasive lumbar fusion. The preoperative single dose administration of methadone has already been shown to be effective in improving post operative pain control in open multi-level spinal fusion patient populations and has become the standard of care in most surgical centers across the country. The long half-life of methadone results in improved steady state pharmacokinetics relative to other traditional opioids and is thought to improve pain control while decreasing consumption. In addition to Mu opioid receptor agonism, Methadone is thought to also have adjunctive analgesic and anti-tolerance effects due to CNS excitatory glutamatergic NMDA receptor antagonism. There are also reports of synergistic effects from serotonin and norepinephrine reuptake inhibition.

The investigators predict that a single preoperative oral methadone administration can result in improved postoperative analgesia with requirement of less IV and PO traditional narcotics within the first 2 weeks post operatively and also will not increase co-morbid risks relative to traditional shorter acting opioid analgesics that are presently given preoperatively.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 1

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age: 18 - 70
• Will undergo one level minimally invasive lumbar fusion surgery
• Primary symptoms are back and/or leg pain

Exclusion Criteria:

• Preoperative chronic renal insufficiency or failure (defined as a serum creatinine more than 2 mg/dl)
• Significant liver disease (cirrhosis or hepatic failure)
• American Society of Anesthesiologists (ASA) physical status IV or V
• Pulmonary disease necessitating home oxygen therapy
• Patients with acute bronchial asthma or hypercarbia
• Patient who has or is suspected of having a paralytic ileus
• Preoperative use of methadone or hydromorphone
• Known hypersensitivity to methadone
• Known hypersensitivity to oxycodone
• Recent history of opioid or alcohol abuse
• Inability to use a PCA device
• Inability to speak English
• Any patient judged by the anesthesia care team to potentially require prolonged postoperative intubation
• Participation in another clinical trial
• Inability of patient to provide study informed consent (including patients who are cognitively impaired)
• Presence of drug interaction between methadone/oxycodone and patient's regular or PRN medications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Methadone; This cohort will receive oral methadone 15mg po tablet pre-operatively	Drug: Methadone Hydrochloride; FDA approved medication to treat pain
Active Comparator: Oxycodone; This cohort will receive oxycodone/acetaminophen 10/325 po tablet pre-operatively	Drug: Oxycodone-Acetaminophen; FDA approved medication to treat pain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative in-hospital patient's narcotic requirement	The total Morphine Milligram Equivalent (MME) for each post-operative day	Post-operative day 0 to 4
Improvement in low back pain between the two cohorts as assessed by Oswestry Disbility Index (ODI)	Change in ODI (scale from 0 to 100) from pre-op to post-op (14 days post-op)	14 days

Collaborators and Investigators

• Sponsor: The Methodist Hospital Research Institute
• Investigators: Principal Investigator: Sean M Barber, MD, The Methodist Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Anticipated): February 11, 2020
• Primary Completion (Anticipated): December 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: September 27, 2019
• First Submitted That Met QC Criteria: September 30, 2019
• First Posted (Actual): October 2, 2019

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 28, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: lateral lumbar interbody fusion; minimally invasive spinal surgery
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Spinal Diseases; Bone Diseases; Spondylolysis; Spondylosis; Intervertebral Disc Degeneration; Spondylolisthesis; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antipyretics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Acetaminophen; Oxycodone; Methadone; Acetaminophen, hydrocodone drug combination
• Other Study ID Numbers: Pro00022567

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: No plans to share IPD at the moment

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes