Recruiting
Early Phase 1

Methadone vs. Morphine

Sponsor:

University of Virginia

Code:

NCT06387303

Conditions

Pain, Postoperative

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Methadone

Morphine

Study Details

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

Study ID

NCT06387303

Start date

Aug 6, 2024

Status verified date

Aug, 2024

Completion date

May 11, 2026

Anticipated

Primary completion date

May 11, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Health Services Research

Interventions and Outcome Measures

Arms

active comparator: Intrathecal Morphine

250 mcg Intrathecal Injection prior to incision

experimental: Intravenous Methadone

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

Interventions

Methadone

Intravenous Methadone

Morphine

Intrathecal Morphine

Primary outcome measure

  • Quality of Recovery 15 score [ Time Frame: 24 hours, 48 hours, 72 hours, 42 days, 92 days ]
  • Overall Benefits of Analgesic Score [ Time Frame: 24 hours, 48 hours, 72 hours, 42 days, 92 days ]
  • morphine milligram equivalent [ Time Frame: 24 hours, 48 hours, 72 hours ]
  • Numeric Rating Scale pain scores (NRS) [ Time Frame: 24 hours, 48 hours, 72 hours ]

Central Contacts and Locations

Central contacts

Locations

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22908-0710

Contacts

More Information

Sponsor

University of Virginia

Last update posted

Aug 11, 2025

Last verified

Aug, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Virginia on 2025-08-11.