Recruiting
Early Phase 1

Methadone vs. Remifentanil

Sponsor:

University of Virginia

Code:

NCT06810336

Conditions

Brain Injury

Brain Tumors

Craniotomy Surgery

Pain

Postoperative

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Remifentanil

Methadone

Study Details

Brief summary:

Postoperative pain is prevalent after intracranial surgery. Patients undergoing craniotomy are typically managed with short acting opioids to enable early and reliable post-operative neurological exam as well as avoid the risk of respiratory depression. However, a plethora of studies have shown that a majority of these patients experience moderate to severe pain in first 48 hours after surgery. Suboptimal pain control can lead to complications such as arterial hypertension and post-operative intracranial hemorrhage, and hence, increased morbidity and mortality.

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 that underwent orthopedic, abdominal, complex spine, and cardiac surgery. Similar findings have been shown in obstetric patients that underwent caesarean delivery under general anesthesia as well as patients that underwent gynecologic surgery and received IV methadone intraoperatively.

In a recently published retrospective study, a single intraoperative dose of IV methadone was well tolerated with lower pain scores as well as MME (oral morphine milligram equivalents) requirements for up to 72 hours after elective intracranial surgery.

IV methadone has, however, never been compared with conventional management via IV remifentanil for functional recovery in patients undergoing elective intercranial surgery.

The investigator's hypothesis is that intravenous (IV) methadone is non-inferior to IV remifentanil in patients who undergo elective intracranial surgery. It offers the advantage of being a single dose noninvasive analgesic modality that may contribute to decreasing MME consumption during the first 72 hours postoperatively, controlling postoperative pain, and improving quality of recovery after surgery.

Conditions

Brain Injury

Brain Tumors

Craniotomy Surgery

Pain

Postoperative

Study ID

NCT06810336

Start date

Mar 10, 2025

Status verified date

Apr, 2026

Completion date

Sep 10, 2027

Anticipated

Primary completion date

Sep 10, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. Adult Patients between ages 18 and 65 years old.
2. Undergoing supratentorial intracranial surgery
3. American Society of Anesthesiologists (ASA) physiological status I-III
4. Body Mass Index (BMI) between 18.5 and 45
5. Ability to understand and read English

Exclusion Criteria:

1. Being unable or unwilling to sign a consent
2. Anticipated discharge within 24 hours after surgery
3. Patients requiring Emergent Surgery
4. Preoperative usage of Methadone, or allergy to it.
5. Patients with chronic pain, requiring daily opioid use at the time of surgery, MME >60 as FDA defines opioid tolerant as 60 MME, long-acting forms of opioids such as fentanyl patch, oxycontin
6. 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
7. Preoperative chronic renal insufficiency or failure (defined as a serum creatinine more than 2 mg/dl),
8. Pregnancy
9. Significant liver disease (cirrhosis or hepatic failure)
10. QTc >450 on preoperative electrocardiogram
11. Pulmonary disease necessitating home oxygen therapy
12. Inability to speak or read the English language

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Health Services Research

Interventions and Outcome Measures

Arms

active comparator: IV Remifentanil

titratable medication, dosage determined by anesthesia care team.

experimental: IV Methadone

0.2 mg / kg Intravenous delivery prior to incision

Interventions

Remifentanil

Intravenous Remifentanil

Methadone

Intravenous Methadone

Primary outcome measure

  • Quality of recovery after surgery on postoperative day 1,2,3 using QoR-15 psychometrical questionnaire (range 0-150). [ 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

Jennifer Phillips, RN

434-297-8136JVP8A@virginia.edu

Lauren Dunn, M.D.

lak3r@uvahealth.org

Principal Investigator:

Lauren K Dunn, MD

More Information

Sponsor

University of Virginia

Last update posted

May 4, 2026

Last verified

Apr, 2026

Keywords

  • craniotomy

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 2026-05-04.