The Impact of Intraoperative Methadone on Postoperative Opioid Use

NCT07092475 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: HCI182069
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-institution, randomized controlled trial to assess the effectiveness of intraoperative methadone on postoperative opioid use, pain control, and recovery in patients undergoing autologous breast reconstruction. Findings from this trial would inform subsequent perioperative pain protocols and allow the possible integration of intraoperative methadone into multimodal analgesia protocols.

Conditions

Breast Cancer; Opioid Use

Outcome Measures

Primary Outcomes (1)

• Total Postoperative Opioid Use

  To evaluate the impact of intraoperative methadone administration on postoperative opioid use and pain control in patients undergoing autologous breast reconstruction. Total perioperative opioid consumption will be measured in morphine milligram equivalents (MMEs), a standardized measure to quantify the strength of opioid doses compared to morphine. This outcome measure will be assessed from the day of surgery until discharge, up to 4 weeks.

  from the day of surgery until discharge, up to 4 weeks.

Secondary Outcomes (9)

• Patient-Reported Pain Scores - Visual Analog Scale

  from the day of surgery until discharge, up to 4 weeks.

• Patient-Reported Pain Scores - Pain Interference Score

  from the day of surgery until discharge, up to 4 weeks.

• Patient-Reported Pain Scores - Patient Pain Management Satisfaction Scale

  from the day of surgery until discharge, up to 4 weeks.

• Length of hospital stay

  from the day of surgery until discharge, up to 4 weeks.

• Proportion of participants utilizing non-opioid analgesics

  from the day of surgery until discharge, up to 4 weeks.

Study Arms (2)

Intraoperative Methadone

EXPERIMENTAL

the methadone group will receive a single dose of intravenous methadone administered within 30 minutes after induction of anesthesia by the attending anesthesiologist. The standard dose will be 20 mg, except for patients under 60 kg or over 65 years of age, who will receive 15 mg.

Drug: Methadon

Control

NO INTERVENTION

The control group will not receive methadone and will instead receive a standard dose of 1 mg IV hydromorphone within the final 30-45 minutes of the procedure.

Interventions

Methadon DRUG

A long-acting synthetic opioid with a pharmacologic profile that potentially offers more stable and longer-lasting pain relief.

Also known as: Diskets, Methadone Intensol, Methadose

Intraoperative Methadone

Eligibility Criteria

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

You may qualify if:

• Female patients 18 years of age or older
• Patients undergoing unilateral or bilateral autologous breast reconstruction with abdominally-based free flaps after mastectomy for breast cancer or cancer prophylaxis

You may not qualify if:

• Patients undergoing reoperations such as autologous breast reconstruction as a revision procedure following failed implant-based reconstruction
• Patients undergoing multiple procedures such as mastectomy and immediate reconstruction
• Patients with documented chronic opioid use prior to procedure, or chronic pain condition

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Joy Ha

Salt Lake City, Utah, 84112, United States

Location

Related Publications (41)

• CfDCa Prevention: Opioids. https://www.cdc.gov/opioids/index.html. Accessed October 26, 2021.

  BACKGROUND

• Hah JM, Bateman BT, Ratliff J, Curtin C, Sun E. Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic. Anesth Analg. 2017 Nov;125(5):1733-1740. doi: 10.1213/ANE.0000000000002458.

  PMID: 29049117 BACKGROUND

• Olds C, Spataro E, Li K, Kandathil C, Most SP. Assessment of Persistent and Prolonged Postoperative Opioid Use Among Patients Undergoing Plastic and Reconstructive Surgery. JAMA Facial Plast Surg. 2019 Jul 1;21(4):286-291. doi: 10.1001/jamafacial.2018.2035.

  PMID: 30844024 BACKGROUND

• Mercadante S. Intravenous Methadone for Perioperative and Chronic Cancer Pain: A Review of the Literature. Drugs. 2023 Jul;83(10):865-871. doi: 10.1007/s40265-023-01876-7. Epub 2023 Jun 13.

  PMID: 37308798 BACKGROUND

• Barker JC, DiBartola K, Wee C, Andonian N, Abdel-Rasoul M, Lowery D, Janis JE. Preoperative Multimodal Analgesia Decreases Postanesthesia Care Unit Narcotic Use and Pain Scores in Outpatient Breast Surgery. Plast Reconstr Surg. 2018 Oct;142(4):443e-450e. doi: 10.1097/PRS.0000000000004804.

  PMID: 29979365 BACKGROUND

• Muetterties CE, Taylor JM, Kaeding DE, Morales RR, Nguyen AV, Kwan L, Tseng CY, Delong MR, Festekjian JH. Enhanced Recovery after Surgery Protocol Decreases Length of Stay and Postoperative Narcotic Use in Microvascular Breast Reconstruction. Plast Reconstr Surg Glob Open. 2023 Dec 14;11(12):e5444. doi: 10.1097/GOX.0000000000005444. eCollection 2023 Dec.

  PMID: 38098953 BACKGROUND

• Gort N, van Gaal BGI, Tielemans HJP, Ulrich DJO, Hummelink S. Positive effects of the enhanced recovery after surgery (ERAS) protocol in DIEP flap breast reconstruction. Breast. 2021 Dec;60:53-57. doi: 10.1016/j.breast.2021.08.010. Epub 2021 Aug 20.

  PMID: 34464847 BACKGROUND

• Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633.

  PMID: 25837528 BACKGROUND

• Kharasch ED, Brunt LM, Blood J, Komen H. Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double-blinded, Dose-finding Pilot Study. Anesthesiology. 2023 Oct 1;139(4):405-419. doi: 10.1097/ALN.0000000000004663.

  PMID: 37350677 BACKGROUND

• Udelsmann A, Maciel FG, Servian DC, Reis E, de Azevedo TM, Melo Mde S. Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting. Rev Bras Anestesiol. 2011 Nov-Dec;61(6):695-701. doi: 10.1016/S0034-7094(11)70078-2. English, Multiple languages.

  PMID: 22063370 BACKGROUND

• Carle N, Nikolajsen L, Uhrbrand CG. Respiratory Depression Following Intraoperative Methadone: A Retrospective Cohort Study. Anesth Analg. 2025 Mar 1;140(3):516-523. doi: 10.1213/ANE.0000000000007018. Epub 2025 Feb 14.

  PMID: 38814334 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

• Bernstein JL, Lu Wang M, Huang H, Otterburn DM. Intra-operative Methadone Decreases Post-operative Pain and Opioid Use in DIEP Flap Breast Patients: A New ERAS Protocol. Plast Reconstr Surg Glob Open. 2022;10(10 Suppl):92. Published 2022 Oct 24. doi:10.1097/01.GOX.0000898792.35273.f6

  BACKGROUND

• NIDA. Drug Overdose Deaths: Facts and Figures. National Institute on Drug Abuse website. https://nida.nih.gov/research-topics/trends-statistics/overdose-death-rates. August 21, 2024 Accessed November 12, 2024.

  BACKGROUND

• Centers for Disease Control and Prevention. State Unintentional Drug Overdose Reporting System (SUDORS). Preliminary Data. Atlanta, GA: US Department of Health and Human Services, CDC; November 12, 2024. Access at: https://www.cdc.gov/overdose-prevention/data-research/facts-stats/sudors-dashboard-fatal-overdose-data.html

  BACKGROUND

• Florence C, Luo F, Rice K. The economic burden of opioid use disorder and fatal opioid overdose in the United States, 2017. Drug Alcohol Depend. 2021 Jan 1;218:108350. doi: 10.1016/j.drugalcdep.2020.108350. Epub 2020 Oct 27.

  PMID: 33121867 BACKGROUND

• Meyer R, Patel AM, Rattana SK, Quock TP, Mody SH. Prescription opioid abuse: a literature review of the clinical and economic burden in the United States. Popul Health Manag. 2014 Dec;17(6):372-87. doi: 10.1089/pop.2013.0098.

  PMID: 25075734 BACKGROUND

• Sun EC, Darnall BD, Baker LC, Mackey S. Incidence of and Risk Factors for Chronic Opioid Use Among Opioid-Naive Patients in the Postoperative Period. JAMA Intern Med. 2016 Sep 1;176(9):1286-93. doi: 10.1001/jamainternmed.2016.3298.

  PMID: 27400458 BACKGROUND

• Alam A, Gomes T, Zheng H, Mamdani MM, Juurlink DN, Bell CM. Long-term analgesic use after low-risk surgery: a retrospective cohort study. Arch Intern Med. 2012 Mar 12;172(5):425-30. doi: 10.1001/archinternmed.2011.1827.

  PMID: 22412106 BACKGROUND

• Goldberg RF. The Opioid Crisis: The Surgeon's Role. Adv Surg. 2019 Sep;53:305-325. doi: 10.1016/j.yasu.2019.04.015. Epub 2019 May 17. No abstract available.

  PMID: 31327454 BACKGROUND

• Theisen K, Jacobs B, Macleod L, Davies B. The United States opioid epidemic: a review of the surgeon's contribution to it and health policy initiatives. BJU Int. 2018 Nov;122(5):754-759. doi: 10.1111/bju.14446. Epub 2018 Jul 26.

  PMID: 29896932 BACKGROUND

• Murphy GS, Szokol JW. Intraoperative Methadone in Surgical Patients: A Review of Clinical Investigations. Anesthesiology. 2019 Sep;131(3):678-692. doi: 10.1097/ALN.0000000000002755. No abstract available.

  PMID: 31094758 BACKGROUND

• Lai G, Aroke EN, Zhang SJ. Rediscovery of Methadone to Improve Outcomes in Pain Management. J Perianesth Nurs. 2022 Aug;37(4):425-434. doi: 10.1016/j.jopan.2021.08.011. Epub 2022 Apr 6.

  PMID: 35396188 BACKGROUND

• Temple-Oberle C, Shea-Budgell MA, Tan M, Semple JL, Schrag C, Barreto M, Blondeel P, Hamming J, Dayan J, Ljungqvist O; ERAS Society. Consensus Review of Optimal Perioperative Care in Breast Reconstruction: Enhanced Recovery after Surgery (ERAS) Society Recommendations. Plast Reconstr Surg. 2017 May;139(5):1056e-1071e. doi: 10.1097/PRS.0000000000003242.

  PMID: 28445352 BACKGROUND

• Jablonka EM, Lamelas AM, Kim JN, Molina B, Molina N, Okwali M, Samson W, Sultan MR, Dayan JH, Smith ML. Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following Abdominally Based Microsurgical Breast Reconstruction. Plast Reconstr Surg. 2017 Aug;140(2):240-251. doi: 10.1097/PRS.0000000000003508.

  PMID: 28746269 BACKGROUND

• Carron M, Tamburini E, Linassi F, Pettenuzzo T, Boscolo A, Navalesi P. Efficacy of nonopioid analgesics and adjuvants in multimodal analgesia for reducing postoperative opioid consumption and complications in obesity: a systematic review and network meta-analysis. Br J Anaesth. 2024 Dec;133(6):1234-1249. doi: 10.1016/j.bja.2024.08.009. Epub 2024 Oct 3.

  PMID: 39366846 BACKGROUND

• Tageza Ilala T, Teku Ayano G, Ahmed Kedir Y, Tamiru Mamo S. Evidence-Based Guideline on the Prevention and Management of Perioperative Pain for Breast Cancer Peoples in a Low-Resource Setting: A Systematic Review Article. Anesthesiol Res Pract. 2023 Nov 3;2023:5668399. doi: 10.1155/2023/5668399. eCollection 2023.

  PMID: 37953883 BACKGROUND

• Baratta JL, Schwenk ES, Viscusi ER. Clinical consequences of inadequate pain relief: barriers to optimal pain management. Plast Reconstr Surg. 2014 Oct;134(4 Suppl 2):15S-21S. doi: 10.1097/PRS.0000000000000681.

  PMID: 25254999 BACKGROUND

• Lawal OD, Gold J, Murthy A, Ruchi R, Bavry E, Hume AL, Lewkowitz AK, Brothers T, Wen X. Rate and Risk Factors Associated With Prolonged Opioid Use After Surgery: A Systematic Review and Meta-analysis. JAMA Netw Open. 2020 Jun 1;3(6):e207367. doi: 10.1001/jamanetworkopen.2020.7367.

  PMID: 32584407 BACKGROUND

• Glowacki D. Effective pain management and improvements in patients' outcomes and satisfaction. Crit Care Nurse. 2015 Jun;35(3):33-41; quiz 43. doi: 10.4037/ccn2015440.

  PMID: 26033099 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

• Sunilkumar MM, Lockman K. Practical Pharmacology of Methadone: A Long-acting Opioid. Indian J Palliat Care. 2018 Jan;24(Suppl 1):S10-S14. doi: 10.4103/IJPC.IJPC_180_17.

  PMID: 29497249 BACKGROUND

• Hanna V, Senderovich H. Methadone in Pain Management: A Systematic Review. J Pain. 2021 Mar;22(3):233-245. doi: 10.1016/j.jpain.2020.04.004. Epub 2020 Jun 26.

  PMID: 32599153 BACKGROUND

• Komen H, Brunt LM, Deych E, Blood J, Kharasch ED. Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study. Anesth Analg. 2019 Apr;128(4):802-810. doi: 10.1213/ANE.0000000000003464.

  PMID: 29847382 BACKGROUND

• Broyles JM, Balk EM, Adam GP, Cao W, Bhuma MR, Mehta S, Dominici LS, Pusic AL, Saldanha IJ. Implant-based versus Autologous Reconstruction after Mastectomy for Breast Cancer: A Systematic Review and Meta-analysis. Plast Reconstr Surg Glob Open. 2022 Mar 11;10(3):e4180. doi: 10.1097/GOX.0000000000004180. eCollection 2022 Mar.

  PMID: 35291333 BACKGROUND

• Jacobs A, Lemoine A, Joshi GP, Van de Velde M, Bonnet F; PROSPECT Working Group collaborators#. PROSPECT guideline for oncological breast surgery: a systematic review and procedure-specific postoperative pain management recommendations. Anaesthesia. 2020 May;75(5):664-673. doi: 10.1111/anae.14964. Epub 2020 Jan 26.

  PMID: 31984479 BACKGROUND

• Roth RS, Lowery JC, Davis J, Wilkins EG. Persistent pain following postmastectomy breast reconstruction: long-term effects of type and timing of surgery. Ann Plast Surg. 2007 Apr;58(4):371-6. doi: 10.1097/01.sap.0000239810.38137.84.

  PMID: 17413877 BACKGROUND

• Cata JP, Zaidi Y, Guerra-Londono JJ, Kharasch ED, Piotrowski M, Kee S, Cortes-Mejia NA, Gloria-Escobar JM, Thall PF, Lin R. Intraoperative methadone administration for total mastectomy: A single center retrospective study. J Clin Anesth. 2024 Nov;98:111572. doi: 10.1016/j.jclinane.2024.111572. Epub 2024 Aug 23.

  PMID: 39180867 BACKGROUND

• Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.

  PMID: 38572751 BACKGROUND

• Gordon DB, Dahl JL, Miaskowski C, McCarberg B, Todd KH, Paice JA, Lipman AG, Bookbinder M, Sanders SH, Turk DC, Carr DB. American pain society recommendations for improving the quality of acute and cancer pain management: American Pain Society Quality of Care Task Force. Arch Intern Med. 2005 Jul 25;165(14):1574-80. doi: 10.1001/archinte.165.14.1574.

  PMID: 16043674 BACKGROUND

• Jensen MP, Chen C, Brugger AM. Interpretation of visual analog scale ratings and change scores: a reanalysis of two clinical trials of postoperative pain. J Pain. 2003 Sep;4(7):407-14. doi: 10.1016/s1526-5900(03)00716-8.

  PMID: 14622683 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Amidines; Methadone

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Organic Chemicals; Ketones

Study Officials

• Alvin Kwok, MD, MPH

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: The anesthesiology provider assigned to the patient's surgery will be notified of which treatment arm the patient is assigned to by the research coordinator or by the Director of Anesthesia Services on the day of surgery. The reconstructive surgeon and all other hospital staff (e.g. nurses) will be blinded to what treatment arm the patient was assigned.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2025
• First Posted: July 30, 2025
• Study Start: November 1, 2025
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)