Head and Neck CarcinomaPhase 4NCT07857655
Intraoperative Methadone for the Management of Postoperative Pain in Patients With Head and Neck Cancers
A Phase 4 study testing Electronic Health Record Review, Fentanyl and Laryngoscopy in people with Head and Neck Carcinoma and Hypopharyngeal Carcinoma, run by OHSU Knight Cancer Institute at 1 site in United States.
Trial summary
This phase IV trial compares how well methadone plus standard fentanyl given during surgery (intraoperative) works compared to intraoperative standard fentanyl alone in managing pain after surgery (postoperative) among patients with head and neck cancers. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- Head and Neck Carcinoma, Hypopharyngeal Carcinoma, Laryngeal Carcinoma
- What is being tested?
- Electronic Health Record Review, Fentanyl and Laryngoscopy
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Sep 2026to 29 Jul 2029
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults 18-89
- Patients with biopsy proven head and neck cancer*. Diagnosis will be confirmed by Otolaryngology-Head and Neck Surgery (OTOHNS) team at our center
- Oral cavity, oropharyngeal, hypopharyngeal, laryngeal
- Undergoing surgical intervention with ablative and/or reconstructive OTOHNS surgeons for one of the following:
- Free flap reconstruction (single or double flaps including: radial forearm free flap [RFFF], osteocutaneous radial forearm flap [OCRFF], fibula free flap [FFF], anterolateral thigh [ALT], scapula flap, latissimus, gracilis, rectus sheath, pectoralis)
- Resections with pedicled flaps (e.g., pectoralis major, latissimus) with an expected case time of > 4 hours
- Expected time of surgery is found in the surgery request and in our department, the surgeon puts in these orders
Who cannot join
- Patients will be excluded if they do not consent, are minors, are deemed part of a vulnerable population or lack decision-making capacity
- Current use of long-acting opioids
- Pain patients treated with opioids for pathology unrelated to head and neck cancer and/or chronic pain patients, i.e. chronic back pain
- Positive screening at interview for illicit drug use, not including marijuana
- Drug screening is not routinely acquired prior to anesthesia per our institution's standard of care and policies. Any suspected abuse or use is guided by clinical evaluation. Patients with evidence of acute intoxication or concern for prior abuse history will be excluded per clinical judgement
- Contraindications to methadone (American Society of Addiction Medicine [ASAM] criteria): hypersensitivity, severe respiratory depression, paralytic ileus - in which only hypersensitivity is relevant, since individuals undergoing surgery would not present with the latter
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- Currently on CYP therapies noted in the Food and Drug Administration (FDA) methadone pamphlet to have either decreased efficacy of therapy or reduced metabolism of methadone with concurrent use
- Rifampin, phenytoin, phenobarbital, carbamazepine, voriconazole, abacavir, amprenavir, darunavir+ritonavir, efavirenz, nelfinavir, nevirapine, ritonavir, telaprevir, lopinavir+ritonavir, saquinavir+ritonavir, tipranavir+ritonavir combination, didanosine, stavudine, zidovudine
- Extensive surgical interventions that require additional assistance from outside services at the time of reconstruction (i.e. hypopharyngeal cancer also requiring esophagectomy)
- Head and neck cancers with intracranial components (direct, primary tumor extension, metastatic disease)
- Body mass index (BMI) > 40
- Sleep apnea with an apnea-hypopnea index > 30 without planned tracheostomy
- Stage 3b chronic kidney disease or higher (estimated glomerular filtration rate < 45)
- Aspartate aminotransferase/alanine aminotransferase (AST/ALT) greater than two times the upper limit of normal
- Patients with a history of corrected QT interval (QTc) prolongation > 500 ms
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
OHSU Knight Cancer Institute
Portland, Oregon, 97239
Ryan N. Hellums, 503-494-5355, hellums@ohsu.edu
Ryan N. Hellums
About this study
Official title: Intraoperative Methadone for Postoperative Pain Management in a Head and Neck Oncology Population - A Prospective, Randomized Controlled Trial
This phase IV trial compares how well methadone plus standard fentanyl given during surgery (intraoperative) works compared to intraoperative standard fentanyl alone in managing pain after surgery (postoperative) among patients with head and neck cancers. For most head and neck cancers, the standard treatment is surgery to remove the cancer followed by surgical reconstruction, which often requires tissue harvested from another part of the body-known as a "free flap tissue transfer". These procedures are highly complex, demand a two-surgeon team, and often take many hours to complete. The combination of multiple operative sites and extent of the surgery contributes to significant postoperative pain. Methadone is not yet used in the head and neck population but has been utilized in other subspecialties like spine and cardiac surgery. The benefits of methadone may include improved pain control in the first 72 hours postoperatively requiring less opioids postoperatively and improvement in overall pain scores. Giving intraoperative methadone plus standard fentanyl may work better than fentanyl alone in managing postoperative pain among patients with head and neck cancers.
Read the detailed description
PRIMARY OBJECTIVE:
- To assess the effectiveness of intraoperative methadone compared to control in reducing the requirements of morphine milliequivalents (MMEs).
SECONDARY OBJECTIVES:
- To assess the effectiveness of intraoperative methadone compared to control in reducing objective measures of pain, including MMEs, for up to 72 hours postoperatively.
II. To assess how soon after surgery patients require additional opioid administration for those in the methadone group compared to control.
III. To assess whether additional pain management is required less frequently in the methadone group compared to control.
EXPLORATORY OBJECTIVES:
- To assess if there is an increase in the incidence of post-operative emesis events in the methadone group compared to the control.
II. To assess the effectiveness of intraoperative methadone compared to control on patient's pain scores daily.
III. To assess whether there is a difference in respiratory status between the methadone group compared to the control.
IV. To assess whether higher rates of naloxone administration are required in the methadone group.
- To assess if pain control impacted acute recovery more effectively in the methadone group compared to control.
VI. Clinical outcomes that are standard of care may be assessed. VII. To assess if there is any impact on pain at ~1 month postoperatively compared to the control group.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive methadone intravenously (IV) at the time of incision during standard of care (SOC) surgery. Patients also receive SOC fentanyl prior to SOC laryngoscopy procedure.
ARM II: Patients receive SOC fentanyl prior to SOC laryngoscopy procedure and surgery.
After completion of study intervention, patients are followed up at 4-6 weeks.
- Conditions
- Head and Neck Carcinoma, Hypopharyngeal Carcinoma, Laryngeal Carcinoma, Oral Cavity Carcinoma, Oropharyngeal Carcinoma
- Being tested
- Electronic Health Record Review, Fentanyl, Laryngoscopy, Methadone, Surgical Procedure
- Medical subject headings
- Hypopharyngeal Neoplasms, Laryngeal Neoplasms, Mouth Neoplasms, Oropharyngeal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electronic Health Record ReviewOther
Ancillary studies
FentanylDrug
Also called Abstral, Duragesic
Given SOC fentanyl
LaryngoscopyDevice
Undergo SOC laryngoscopy
MethadoneDrug
Given IV
Surgical ProcedureProcedure or surgery
Also called Operation, Surgery, Surgery Type, Surgery, NOS
Undergo SOC surgery
Survey AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (methadone, fentanyl) | Experimental | Patients receive methadone IV at the time of incision during SOC surgery. Patients also receive SOC fentanyl prior to SOC laryngoscopy procedure. Receives: Other: Electronic Health Record Review; Drug: Fentanyl; Device: Laryngoscopy; Drug: Methadone; Procedure: Surgical Procedure; Other: Survey Administration |
| Arm II (fentanyl) | Active comparator | Patients receive SOC fentanyl prior to SOC laryngoscopy procedure and surgery. Receives: Other: Electronic Health Record Review; Drug: Fentanyl; Device: Laryngoscopy; Procedure: Surgical Procedure; Other: Survey Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total morphine milligram equivalents (MMEs) administered in the first 24 hours postoperatively
MMEs will be calculated using the Stanford Opioid Equivalent calculator and data is obtained from the medication administration record (MAR) in epic. Out of room is standard terminology for when the patient leaves the operating room and a required timestamp per standard workflows across all institutions. Two-sided two-sample t-test will be used to compare mean MMEs administered in the first 24 hours between the methadone and control groups. If data is right skewed, log transformation will be performed prior to t-test. If severe violation to normality assumption is detected graphically or by Shapiro-Wilk hypothesis test, Wilcoxon rank-sum test will be performed instead.
Measured: From out of room to 24 hours postoperatively
Secondary outcomes (3)
Cumulative MMEs between 24-48 hours postoperatively and 48-72 hours postoperatively
Will be analyzed as the same approaches as the primary endpoint with two-sided two-sample t-test. If data is right skewed, log transformation will be performed prior to t-test. If severe violation to normality assumption is detected graphically or by Shapiro-Wilk hypothesis test, Wilcoxon rank-sum test will be performed instead.
Measured: From 24 hours postoperatively to 72 hours postoperatively
Time to first dose of oral opioid administered & intravenous opioid administered
Will be assessed using a time-to-event analysis (log-rank test) to compare between the two groups.
Measured: From out of room to discharge, an average of 5 days
Acute pain service (APS) consult placement (Yes/No) and outcome of that consult
Chi-squared test (or Fisher's exact test if any expected count is < 5) will be used to compare proportion of APS placement between the two groups. Chi-squared test (or Fisher's exact test if any expected count is < 5) will be used to assess the ambulatory goals comparing the proportion of goals achieved between the two groups on each post-operative day (POD) period. (POD0, POD1 and POD2).
Measured: From out of room to discharge, an average of 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2026
- Study start22 Sep 2026
- Primary completion29 Jul 2029 (estimated)
- Study completion29 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- OHSU Knight Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Oregon Health and Science University
- Responsible party
- Principal investigator, Ryan Hellums, OHSU Knight Cancer Institute
- Investigators
- Ryan N Hellums, Principal investigator, OHSU Knight Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07857655
- Sponsor's protocol ID
- STUDY00029016
- Other IDs
- NCI-2026-06212, STUDY00029016
- Status last verified
- Sep 2026
- First submitted
- 15 Sep 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No