Perioperative Rectal Methadone in Spine Surgery

NCT06843174 | Recruiting Phase 4

• 1 other identifier: P-004
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Patients undergoing spinal surgery require pain control medication after their surgery. Investigators have successfully used intravenous Methadone to manage pain after surgery. However, doctors in Canada do not have the intravenous form of Methadone to prescribe to their patients. The investigators in Canada propose a pilot trial to investigate whether Methadone administered rectally could be used to manage pain after spinal surgery. The main questions are:

• receive either Methadone or placebo during surgery.
• be asked some questions about their pain during days 1 to 3 after surgery
• be contacted by phone to ask about their recovery At this time, the study aims to recruit 40 participants from St. Michael's Hospital, to learn whether it will be feasible to plan a larger study.

Conditions

Spinal Surgery; Post-operative Care; Post-operative Pain Management

Keywords

Intraoperative Methadone; Rectal Methadone administration; spinal surgery post-operative pain management

Outcome Measures

Primary Outcomes (2)

• Feasibility to recruit 40 participants into a trial of methadone and placebo

  Recruitment rate (Acceptability and feasibility study)

  18 months

• Feasibility to recruit 40 participants into a trial of methadone and placebo

  Withdrawal rate (Acceptability and feasibility study)

  18 months

Secondary Outcomes (6)

• Adverse outcomes

  At 24, 48, and 72 hours post operative

• Adverse outcomes

  At 24, 48, and 72 hours post operative

• Opioid reduction

  At 24, 48, and 72 hours post operative

• Pain intensity after surgery

  At 24, 48, and 72 hours post operative

• Quality of Recovery

  At 24, 48, and 72 hours post operative

Study Arms (2)

Intervention Arm with Methadone

EXPERIMENTAL

During the spinal surgery intervention, participants receive a single dose of 0.2mg/kg of Methadone rectally, after anesthesia induction.

Drug: Rectal Methadone administer during spinal surgery

Placebo arm

PLACEBO COMPARATOR

During the spinal surgery intervention, participants receive a single dose of saline solution rectally after anesthesia induction.

Other: Placebo: Rectal saline solution

Interventions

Rectal Methadone administer during spinal surgery DRUG

Rectal Methadone administered during spinal surgery for post-operative pain management

Intervention Arm with Methadone

Placebo: Rectal saline solution OTHER

Placebo: Rectal saline solution single dose received during surgery

Placebo arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 65 years-old.
• Elective spinal surgery with fusion of one or more sacral, lumbar, thoracic, and/or cervical levels
• Capacity to provide informed consent
• For participants of childbearing potential, use of contraception.

You may not qualify if:

• American Society of Anesthesiologists Physical Status \> IV
• Hypersensitivity to the active substance (methadone hydrochloride) or other opioid analgesics or to any ingredient in the formulation
• Pregnant or nursing participants
• Known or suspected mechanical gastrointestinal obstruction
• Acute respiratory depression, elevated carbon dioxide levels in the blood, cor pulmonale, or pulmonary disease necessitating home oxygen therapy
• Acute alcohol intoxication, delirium tremens, and convulsive disorders secondary to alcohol intoxication
• Severe central nervous system depression, increased intracranial pressure, or head injury
• Use of monoamine oxidase (MAO) inhibitors, such as isocarboxazid, phenelzine, selegiline, and tranylcypromine, within 14 days of enrollment
• Diarrhea associated with pseudomembranous colitis caused by cephalosporins, lincomycins, or penicillins
• Preoperative renal insufficiency or failure
• Significant liver disease (cirrhosis or hepatic failure)
• History of opioid use disorder within the last 3 months
• Patients taking more than 90 mg of morphine equivalents daily
• Poor comprehension of the English language
• Patients who are likely to remain intubated postoperatively

Sponsors & Collaborators

• Unity Health Toronto: lead
• AFP Innovation Fund: collaborator

Study Sites (1)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

RECRUITING

Related Publications (13)

• Dale O, Sheffels P, Kharasch ED. Bioavailabilities of rectal and oral methadone in healthy subjects. Br J Clin Pharmacol. 2004 Aug;58(2):156-62. doi: 10.1111/j.1365-2125.2004.02116.x.

  PMID: 15255797 BACKGROUND

• Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Vender JS, Benson J, Newmark RL. Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Anesthesiology. 2017 May;126(5):822-833. doi: 10.1097/ALN.0000000000001609.

  PMID: 28418966 BACKGROUND

• Machado FC, Vieira JE, de Orange FA, Ashmawi HA. Intraoperative Methadone Reduces Pain and Opioid Consumption in Acute Postoperative Pain: A Systematic Review and Meta-analysis. Anesth Analg. 2019 Dec;129(6):1723-1732. doi: 10.1213/ANE.0000000000004404.

  PMID: 31743194 BACKGROUND

• Murphy GS, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Dickerson D, Bilimoria S, Benson J, Maher CE, Trenk GJ, Teister KJ, Szokol JW. Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery. Anesthesiology. 2020 Feb;132(2):330-342. doi: 10.1097/ALN.0000000000003025.

  PMID: 31939849 BACKGROUND

• Machado FC, Palmeira CCA, Torres JNL, Vieira JE, Ashmawi HA. Intraoperative use of methadone improves control of postoperative pain in morbidly obese patients: a randomized controlled study. J Pain Res. 2018 Oct 2;11:2123-2129. doi: 10.2147/JPR.S172235. eCollection 2018.

  PMID: 30323647 BACKGROUND

• Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.

  PMID: 20418538 BACKGROUND

• Elliott K, Kest B, Man A, Kao B, Inturrisi CE. N-methyl-D-aspartate (NMDA) receptors, mu and kappa opioid tolerance, and perspectives on new analgesic drug development. Neuropsychopharmacology. 1995 Dec;13(4):347-56. doi: 10.1016/0893-133X(95)00083-P.

  PMID: 8747759 BACKGROUND

• Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, Vallejo R. Opioid complications and side effects. Pain Physician. 2008 Mar;11(2 Suppl):S105-20.

  PMID: 18443635 BACKGROUND

• American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012 Feb;116(2):248-73. doi: 10.1097/ALN.0b013e31823c1030. No abstract available.

  PMID: 22227789 BACKGROUND

• Weir S, Samnaliev M, Kuo TC, Ni Choitir C, Tierney TS, Cumming D, Bruce J, Manca A, Taylor RS, Eldabe S. The incidence and healthcare costs of persistent postoperative pain following lumbar spine surgery in the UK: a cohort study using the Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES). BMJ Open. 2017 Sep 11;7(9):e017585. doi: 10.1136/bmjopen-2017-017585.

  PMID: 28893756 BACKGROUND

• Gerbershagen HJ, Aduckathil S, van Wijck AJ, Peelen LM, Kalkman CJ, Meissner W. Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology. 2013 Apr;118(4):934-44. doi: 10.1097/ALN.0b013e31828866b3.

  PMID: 23392233 BACKGROUND

• Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017 Sep 25;10:2287-2298. doi: 10.2147/JPR.S144066. eCollection 2017.

  PMID: 29026331 BACKGROUND

• Puvanesarajah V, Liauw JA, Lo SF, Lina IA, Witham TF, Gottschalk A. Analgesic therapy for major spine surgery. Neurosurg Rev. 2015 Jul;38(3):407-18; discussion 419. doi: 10.1007/s10143-015-0605-7. Epub 2015 Feb 14.

  PMID: 25680636 BACKGROUND

Study Officials

• Sergio Pereira, MD PhD

  St. Michael's Hospital. Unity Health Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sergio Pereira, MD PhD

CONTACT

416-360-4000; Sergio.Pereira@unityhealth.to

Janneth A Pazmino-Canizares, MSc

CONTACT

4168646060; Janneth.Pazmino-Canizares@unityhealth.to

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo control trial

Study Record Dates

• First Submitted: February 11, 2025
• First Posted: February 24, 2025
• Study Start: February 19, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)