Perioperative Rectal Methadone in Spine Surgery

NCT ID: NCT06843174

Last Updated: 2025-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-19

Study Completion Date

2026-08-31

Brief Summary

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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:

1. Are investigators able to recruit participants for this trial and learn from this study to plan a larger trial?
2. Does Methadone administered rectally during surgery, reduce participants' pain intensity, use less pain medication, and have a better recovery after surgery? Investigators will compare Methadone to a placebo (a look-alike substance that contains no drug) to see if Methadone works to manage pain after surgery better than the usual pain management.

Participants will:

* 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.

Detailed Description

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Indication: Adult patients undergoing spine surgery Condition: Perioperative pain management Number of participants 40 Primary outcome Feasibility (recruitment success, consent rate, adherence, patient withdrawal, missing data, adverse outcomes) Secondary outcome 1) Average pain intensity; 2) Rate of respiratory depression and postoperative ileus; 3) Use of opioids in morphine equivalents; 4) Quality of recovery Study design

* Interventional trial
* Allocation: Randomized
* Intervention model: 2-Arm Parallel-Group
* Primary purpose: Feasibility
* Phase: Phase IV

Masking Participants and Outcome Assessors

Study Intervention:

* Intervention Arm: Methadone 0.2mg/kg of ideal body weight via rectal administration + standard or care
* Placebo Arm: Saline solution via rectal administration + standard of care

Follow-Up: Postoperative days 1, 2, 3, and 30

Conditions

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Spinal Surgery Post-operative Care Post-operative Pain Management

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Randomized, placebo control trial
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Intervention Arm with Methadone

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

Group Type EXPERIMENTAL

Rectal Methadone administer during spinal surgery

Intervention Type DRUG

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

Placebo arm

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

Group Type PLACEBO_COMPARATOR

Placebo: Rectal saline solution

Intervention Type OTHER

Placebo: Rectal saline solution single dose received during surgery

Interventions

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Rectal Methadone administer during spinal surgery

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

Intervention Type DRUG

Placebo: Rectal saline solution

Placebo: Rectal saline solution single dose received during surgery

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. 18 to 65 years-old.
2. Elective spinal surgery with fusion of one or more sacral, lumbar, thoracic, and/or cervical levels
3. Capacity to provide informed consent
4. For participants of childbearing potential, use of contraception.

Exclusion Criteria

1. American Society of Anesthesiologists Physical Status \> IV
2. Hypersensitivity to the active substance (methadone hydrochloride) or other opioid analgesics or to any ingredient in the formulation
3. Pregnant or nursing participants
4. Known or suspected mechanical gastrointestinal obstruction
5. Acute respiratory depression, elevated carbon dioxide levels in the blood, cor pulmonale, or pulmonary disease necessitating home oxygen therapy
6. Acute alcohol intoxication, delirium tremens, and convulsive disorders secondary to alcohol intoxication
7. Severe central nervous system depression, increased intracranial pressure, or head injury
8. Use of monoamine oxidase (MAO) inhibitors, such as isocarboxazid, phenelzine, selegiline, and tranylcypromine, within 14 days of enrollment
9. Diarrhea associated with pseudomembranous colitis caused by cephalosporins, lincomycins, or penicillins
10. Preoperative renal insufficiency or failure
11. Significant liver disease (cirrhosis or hepatic failure)
12. History of opioid use disorder within the last 3 months
13. Patients taking more than 90 mg of morphine equivalents daily
14. Poor comprehension of the English language
15. Patients who are likely to remain intubated postoperatively
16. QT interval \> 500ms on preoperative ECG
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AFP Innovation Fund

OTHER

Sponsor Role collaborator

Unity Health Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sergio Pereira, MD PhD

Role: PRINCIPAL_INVESTIGATOR

St. Michael's Hospital. Unity Health Toronto

Locations

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St. Michael's Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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Canada

Central Contacts

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Sergio Pereira, MD PhD

Role: CONTACT

416-360-4000 ext. 49308

Janneth A Pazmino-Canizares, MSc

Role: CONTACT

4168646060 ext. 49561

Facility Contacts

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Sergio Pereira, MD. PhD

Role: primary

416-360-4000 ext. 49803

Janneth Pazmino-Canizares, MSc

Role: backup

4168646060 ext. 49561

References

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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.

Reference Type BACKGROUND
PMID: 15255797 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28418966 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31743194 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31939849 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 30323647 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20418538 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8747759 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18443635 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22227789 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28893756 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23392233 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29026331 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25680636 (View on PubMed)

Other Identifiers

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P-004

Identifier Type: -

Identifier Source: org_study_id

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