Comparing IV methadone versus IV remifentanil for pain and recovery after craniotomy

Pain Control and Quality of Recovery After Intravenous Methadone Versus Intravenous Remifentanil in Craniotomy Surgery

Early Phase 1 Interventional University of Virginia · NCT06810336

This trial will test whether a single dose of IV methadone given during surgery provides better pain control and recovery than IV remifentanil for adults having supratentorial craniotomy.

Quick facts

PhaseEarly Phase 1
Study typeInterventional
Enrollment40 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorUniversity of Virginia Academic / other
Locations1 site (Charlottesville, Virginia)
Trial IDNCT06810336 on ClinicalTrials.gov

What this trial studies

This single-center, early phase 1 interventional trial randomly compares intraoperative IV methadone to IV remifentanil in adult patients undergoing elective supratentorial craniotomy. Participants receive one of the two opioid strategies during surgery and are followed for postoperative pain scores, opioid consumption (MME), nausea/vomiting, and recovery parameters for the early postoperative period. The trial excludes patients on chronic high-dose opioids, those with active substance use disorder, methadone exposure or allergy, emergent surgeries, or significant renal impairment. Safety monitoring emphasizes neurologic exam reliability and respiratory depression given the different opioid profiles.

Who should consider this trial

Good fit: Adults 18–65 undergoing elective supratentorial intracranial surgery with ASA I–III, BMI 18.5–45, able to read English, and not using chronic daily opioids or medications for opioid use disorder are ideal candidates.

Not a fit: Patients on chronic high-dose opioids, active treatment for opioid use disorder, emergent surgical cases, those with methadone use or allergy, or significant renal failure are excluded and unlikely to receive benefit from this protocol.

Why it matters

Potential benefit: If successful, the approach could give longer-lasting pain relief after craniotomy, reduce postoperative opioid needs, and lower pain-related complications.

How similar studies have performed: Previous randomized and observational work in orthopedic, abdominal, spine, cardiac, obstetric, and gynecologic surgeries has shown IV methadone can lower postoperative pain and opioid use, and retrospective data suggest benefit after intracranial surgery, but randomized head-to-head comparisons in craniotomy patients are limited.

Eligibility criteria

Show full inclusion / exclusion criteria
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

Where this trial is running

Charlottesville, Virginia

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Brain InjuryBrain TumorsCraniotomy SurgeryPainPostoperativePostoperative Carecraniotomy
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.