Pain Control and Quality of Recovery After Intravenous Methadone Versus Intrathecal Morphine in Major Abdominal Surgery

NCT06387303 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: HSR230492
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Moderate to severe postoperative pain is relatively common after major abdominal surgery. It is associated with less than optimal surgical experience, poor quality of recovery, and the development of persistent postsurgical pain. Opioids remain a significant component of postoperative pain management. Side effects of opioids used for the treatment of postoperative pain include constipation, pruritus, nausea, and vomiting. Enhanced recovery after surgery (ERAS) protocols involve the utilization of multimodal analgesia. Analgesic techniques used include epidural analgesia, nerve blocks, and Intrathecal (IT) administration of morph ne. IT morphine reduces the postoperative opioid requirement for 18-24 hours after major abdominal surgery and reduces hospital length of stay (LOS) compared with epidural analgesia. A significant number of patients who receive IT morphine still experience moderate to severe postoperative p in. Additionally, many patients refuse the invasive procedure or cannot receive IT morphine due to procedure contraindications, thrombocytopenia, and/or coagulopathy. Intravenous (IV) methadone has a long analgesic half-life and has N-methyl-D-aspartate (NMDA) receptor antagonist and serotonin and norepinephrine reuptake inhibitor (SNRI) properties. It has previously been shown to reduce postoperative opioid requirements, postoperative nausea and vomiting (PONV), and postoperative pain scores in patients who underwent orthopedic, abdominal, complex spine, and cardiac surg ry. Similar findings have been shown in obstetric patients who underwent cesarean delivery under general anesthesia as well as patients who underwent gynecologic surgery. IV methadone has, however, never been compared with IT morphine as a postoperative analgesic. The hypothesis is that intravenous (IV) methadone is non-inferior to IT morphine in patients who undergo major abdominal surg ry. It offers the advantage of being a noninvasive analgesic modality that may contribute to decreasing opioid consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving the quality of recovery after surgery.

Conditions

Pain, Postoperative

Outcome Measures

Primary Outcomes (4)

• Quality of Recovery 15 score

  The Quality of Recovery-15 (QoR-15) scale is a patient-reported outcome measurement of the quality of recovery after surgery and anesthesia. The scale ranges from 0 to 150, with a higher score indicating a better quality of recovery. A score of 0 indicates extremely poor quality of recovery, while a score of 150 indicates excellent quality of recovery. The QoR-15 score can be classified into four severity classes: excellent, good, moderate, and poor recovery.

  24 hours, 48 hours, 72 hours, 42 days, 92 days

• Overall Benefits of Analgesic Score

  The overall benefit of analgesic score (OBAS) is a daily survey that assesses a patient's satisfaction with analgesia, pain intensity, and adverse effects. To compute score, add all scores in items 1-7. Range: \[0 - 28\]. A low score indicates high benefit 1. Rate your current pain at rest on a scale between 0=minimal pain and 4=maximum imaginable pain 2. Grade any distress and bother from vomiting in the past 24 hours (0=not at all to 4=very much) 3. Grade any distress and bother from itching in the past 24 hours (0=not at all to 4=very much) 4. Grade any distress and bother from sweating in the past 24 hours (0=not at all to 4=very much) 5. Grade any distress and bother from freezing in the past 24 hours (0=not at all to 4=very much) 6. Grade any distress and bother from dizziness in the past 24 hours (0=not at all to 4=very much) 7. How satisfied are you with your pain treatment during the past 24 hours (0=not at all to 4= very much)

  24 hours, 48 hours, 72 hours, 42 days, 92 days

• morphine milligram equivalent

  morphine milligram equivalent is a measurement of a given analgesic effect standardized to a milligram of morphine. In other words agent X has the same effect as Y milligrams of morphine.

  24 hours, 48 hours, 72 hours

• Numeric Rating Scale pain scores (NRS)

  The numeric rating scale (NRS) is a pain screening tool commonly used to assess pain severity at a given moment in time. It uses a 0-10 scale, with zero meaning "no pain" and 10 meaning "the worst pain imaginable."

  24 hours, 48 hours, 72 hours

Secondary Outcomes (2)

• McGill Pain questionnaire score

  42 days, 92 days

• Numeric Rating Pain Score (NRS)

  42 days, 92 days

Study Arms (2)

Intrathecal Morphine

ACTIVE COMPARATOR

250 mcg Intrathecal Injection prior to incision

Drug: Morphine

Intravenous Methadone

EXPERIMENTAL

0.2 mg / kg Intravenous delivery prior to incision. Maximum dosage will be 20 mg.

Drug: Methadone

Interventions

Methadone DRUG

Intravenous Methadone

Also known as: Intrathecal Methadone

Intravenous Methadone

Morphine DRUG

Intrathecal Morphine

Also known as: Intravenous Morphine

Intrathecal Morphine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients with an American Society of Anesthesiologists (ASA) physiological status I-III
• Undergoing laparotomy with midline incision
• Body mass index (BMI) between 18.5 and 45
• Ability to understand and read English
• Willingness and ability to comply with scheduled visits and study procedures

You may not qualify if:

• Not able or unwilling to sign consent
• Patients undergoing ambulatory surgery or anticipated to be discharged sooner than 24 hours after surgery
• Patients with chronic pain, requiring daily opioid use at the time of surgery, MME \>60 as the FDA defines opioid tolerant as 60 MME, long-acting forms of opioids such as fentanyl patch, oxycontin.
• Pregnant Women
• Patients requiring emergent surgery
• Contraindications to neuraxial anesthesia including:
• Coagulopathy
• localized infection at the site of injection
• pre-existing spinal pathology, specifically defined as active radiculopathy, severe central canal stenosis in the lumbar region, or an acute fracture in the lumbar region
• length of the QT interval (QTc) \>450 on the most recent preoperative electrocardiogram (EKG)
• Prior spinal fusion
• Active or Prior Substance Use Disorder, undergoing active treatment with Medication of Opioid Use Disorder including methadone (once daily dosing), Buprenorphine (any formulation) and Naltrexone

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908-0710, United States

RECRUITING

Related Publications (16)

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• Modesitt SC, Sarosiek BM, Trowbridge ER, Redick DL, Shah PM, Thiele RH, Tiouririne M, Hedrick TL. Enhanced Recovery Implementation in Major Gynecologic Surgeries: Effect of Care Standardization. Obstet Gynecol. 2016 Sep;128(3):457-66. doi: 10.1097/AOG.0000000000001555.

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  PMID: 29561531 BACKGROUND

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  PMID: 6128949 BACKGROUND

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  PMID: 30323647 BACKGROUND

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  PMID: 20418538 BACKGROUND

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  PMID: 2039637 BACKGROUND

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• Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MC. QTc interval screening in methadone treatment. Ann Intern Med. 2009 Mar 17;150(6):387-95. doi: 10.7326/0003-4819-150-6-200903170-00103. Epub 2009 Jan 19.

  PMID: 19153406 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Methadone; Morphine

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ketones; Organic Chemicals; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Central Study Contacts

Keita Ikeda, PH.D.

CONTACT

9195931174; ki2d@uvahealth.org

Priyanka Singla, M.D.

CONTACT

(434) 982-4310; ps7ey@uvahealth.org

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Anesthesiology

Model Details: a single blind study

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: April 29, 2024
• Study Start: August 6, 2024
• Primary Completion: May 11, 2026
• Study Completion: May 11, 2026
• Last Updated: August 11, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)