Postoperative Oral Methadone After Major Spine Surgery; Safety, Feasibility and Efficacy in Prevention of Progression to Chronic Opioid Usage at 3 Months

Postoperative Oral Methadone After Major Spine Surgery; Safety, Feasibility and Efficacy in Prevention of Progression to Chronic Opioid Usage at 3 Months - A Pilot Trial.

The purpose of this study is to evaluate the feasibility and safety of a clinical protocol based on the administration of intraoperative intravenous methadone followed by a short regimen of oral/IV (if the patient is not able to take oral) methadone following spine surgery and to evaluate if methadone decreases persistent opioid usage at 3 months in comparison to placebo.

Study Overview

• Status: Withdrawn
• Conditions: Spine Surgery
• Intervention / Treatment: Drug: Postoperative methadone; Drug: Rescue Analgesia; Drug: Postoperative placebo

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults undergoing multilevel complex lumbar and/or thoracic spine fusion surgery, including revision surgeries

Exclusion Criteria:

• BMI greater than 40

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Postoperative methadone	Drug: Postoperative methadone; Participants will receive intraoperative methadone (0.2 mg/kg ideal body weight intravenously but not exceeding 20mg) followed by oral/IV methadone postoperatively according to the following scheme: A) Opioid naïve patients will receive 5mg twice daily dosage of methadone on postoperative days 1 and 2 followed by 5 mg daily on postoperative days 3, 4, and 5. B) Patients taking opioids preoperatively will continue to receive their regular opioids and additionally receive 5 mg twice a day of methadone on postoperative days 1 and 2, followed by 5 mg per day on days 3, 4 and 5.; Drug: Rescue Analgesia; PACU analgesia for both groups will be the usual care regime of fentanyl or hydromorphone bolus as prescribed by the physician anesthesiologist doing the case. All patients receive IV intravenous patient-controlled analgesia and rescue opioids which is usual care for postoperative pain.
Placebo Comparator: Postoperative placebo	Drug: Rescue Analgesia; PACU analgesia for both groups will be the usual care regime of fentanyl or hydromorphone bolus as prescribed by the physician anesthesiologist doing the case. All patients receive IV intravenous patient-controlled analgesia and rescue opioids which is usual care for postoperative pain.; Drug: Postoperative placebo; Participants will receive intraoperative methadone intravenously 0.2mg/kg followed by oral placebo postoperatively according to the following scheme: Opioid naïve patients and patients taking opioids preoperatively will receive placebo tablets twice daily on day 1 and day 2 and once daily day 3, 4 and 5. Patients taking preoperative opioids will be able to return to their baseline opioids immediately after surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of study design as assessed by the number of participants for which scheduled postoperative methadone versus placebo were able to be administered according to the scheme described		Day of discharge (about 6 days after surgery)
Feasibility of study design as assessed by number of participants for which safety was able to be assessed (EKGs)		postop days 1 and 5
Feasibility of study design as assessed by the number of participants for which safety was able to be assessed (respiratory events)	ability to evaluate adverse respiratory events	Day of discharge (about 6 days after surgery)
Feasibility of study design as assessed by the number of participants for which postop opioid usage could be surveyed at 3 months		3 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants for which opioid usage was able to be collected		Day of discharge (about 6 days after surgery)
Safety as assessed by the number of patients developing respiratory depression	Saturation of Oxygen(SPO2) less than 85%, Respiratory rate <5 for longer than 3 minutes, ( Khanna et) increased oxygen requirement related to opioid-induced respiratory depression, naloxone use. The SPO2 will be monitored continuously per usual care in post anesthesia care unit (PACU) and every 4 hours in the ward.	by fifth day of hospital stay
Safety as assessed by the number of patients developing clinically significant corrected QT interval(QTc )prolongation	QTc interval >500ms or >25% increase from baseline; number of patients developing arrhythmias needed treatment	by fifth day of hospital stay
Safety as assessed by the number of participants with hallucinations		by fifth day of hospital stay
Safety as assessed by the number of participants with dizziness		by fifth day of hospital stay
Safety as assessed by the number of participants with Antiemetic use		by fifth day of hospital stay
Safety as assessed by the number of participants with occurrence of nausea		by fifth day of hospital stay
Safety as assessed by the number of participants with occurrence of vomiting		by fifth day of hospital stay
Safety as assessed by the number of participants with occurrence of Ileus or constipation		by fifth day of hospital stay
Safety as assessed by the number of subjects with persistent opioid use	This is scored from 0(less than once a week) to 4(constantly, a higher number indicating more opioid use)	3 months after surgery

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Shobana Rajan, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 23, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: opioids
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Methadone
• Other Study ID Numbers: HSC-MS-22-0912

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No