Perioperative Rectal Methadone in Spine Surgery

Обзор

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.

Подробное описание

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

Вмешательства

• Препарат Rectal Methadone administer during spinal surgery
  Rectal Methadone administered during spinal surgery for post-operative pain management
• Другое Placebo: Rectal saline solution
  Placebo: Rectal saline solution single dose received during surgery

Первичные конечные точки

• Feasibility to recruit 40 participants into a trial of methadone and placebo [Срок оценки: 18 months]
• Feasibility to recruit 40 participants into a trial of methadone and placebo [Срок оценки: 18 months]

Вторичные конечные точки (6)

• Adverse outcomes [Срок оценки: At 24, 48, and 72 hours post operative]
• Adverse outcomes [Срок оценки: At 24, 48, and 72 hours post operative]
• Opioid reduction [Срок оценки: At 24, 48, and 72 hours post operative]
• Pain intensity after surgery [Срок оценки: At 24, 48, and 72 hours post operative]
• Quality of Recovery [Срок оценки: At 24, 48, and 72 hours post operative]
• Pain interference [Срок оценки: Difference between Baseline and 30 days after surgery]

Критерии участия

Критерии включения

• 18 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.

Критерии исключения

• 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
• QT interval > 500ms on preoperative ECG

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Поддерживающая терапия

Центры проведения

Канада · 1 центр

• St. Michael's Hospital — Toronto

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT06843174 · P-004

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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