Postoperative PainPhase 4METATONSNCT05445856
Intraoperative Methadone for Postoperative Pain in Patients Undergoing Tonsillectomy
A Phase 4 study testing Methadone and Fentanyl in people with Postoperative Pain, run by University of Aarhus at 1 site in Denmark.
Trial summary
A randomized controlled trial evaluating the efficacy and safety of single-shot intraoperative methadone for postoperative pain in patients undergoing tonsillectomy. Fentanyl is used as an active comparator Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Postoperative Pain
- What is being tested?
- Methadone and Fentanyl
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteDenmark
- Study dates
- 28 Nov 2022to Aug 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- All patients (≥18 years) scheduled for elective tonsillectomy
Who cannot join
- American Society of Anaesthesiologists (ASA) physical status IV or V
- Allergy to study drugs
- Daily use of opioids 7 days prior to surgery
- Inability to provide informed consent
- Severe respiratory insufficiency
- Heart failure
Show all 15Show fewer
- Acute alcohol intoxication/delirium tremens
- Increased intracranial pressure
- Acute liver disease
- Liver insufficiency
- Kidney insufficiency
- Treatment with rifampicin
- Treatment with any drug prolonging the QT-interval
- Pregnancy (every female not using contraceptives will be screened with urine human choriogonadotropin)
- Breastfeeding
Trial locations and contacts
1 site in 1 country.
Denmark1 site, 1 recruiting
- Recruiting
Department of Anaesthesiology and Intensive Care
Randers
Michael Bøndergaard, MD, 51326539, michael.vinther@gmail.com
About this study
Official title: Intraoperative Methadone for Postoperative Pain in Patients Undergoing Tonsillectomy - a Randomized Controlled Trial
A randomized controlled trial evaluating the efficacy and safety of single-shot intraoperative methadone for postoperative pain in patients undergoing tonsillectomy. Fentanyl is used as an active comparator
Read the detailed description
This study is an investigator-initiated, prospective, randomised controlled trial with two arms: an intervention arm (methadone) and a control arm (fentanyl). Patients scheduled for tonsillectomy at Randers Regional Hospital, Denmark, will be approached for study participation.
Patients are randomised in a 1:1 ratio in blocks of varying sizes (between 4 and 8) to receive either intraoperative methadone or fentanyl. The randomisation assignment will be handled by the hospital pharmacy using a web-based central randomisation procedure (www.sealedenvelope.com).
The study drug will be prepared by the hospital pharmacy at Aarhus University Hospital and delivered as kits with identical appearance, marked with the randomization number (1-130). On the day of surgery, a kit will be opened and a 10 ml syringe with study drug (methadone 2 mg/ml or fentanyl 30 microgram/ml or ) will prepared by a health care professional (nurse or medical doctor not involved in the study or the treatment of patients). Once prepared, the blinded study drug will be given to and handled by one of the research team members and administered after induction of anesthesia and prior to surgery
The dose of the study drug will be administered as intravenous bolus dose in equipotent doses (0.2 mg/kg / 3 μg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (women: height (cm) - 105. Men: height (cm) - 100)) after induction of anaesthesia and before the start of surgery.
Postoperative data will be obtained by reviewing hospital records, by interview and electronic questionnaires sent by email.
- Conditions
- Postoperative Pain
- Being tested
- Methadone, Fentanyl
- Keywords
- Postoperative pain, Methadone
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MethadoneDrug
Methadone is administered as a single intravenous dose after induction of anesthesia and prior to initiation of surgery
FentanylDrug
Fentanyl is administered as a single intravenous dose after induction of anesthesia and prior to initiation of surgery
| Study group | Role | What they receive |
|---|---|---|
| Methadone | Experimental | Single-shot intravenous methadone 0.2 mg/kg administered intraoperatively Receives: Drug: Methadone |
| Fentanyl | Active comparator | Single-shot intravenous fentanyl 3 microgram/kg administered intraoperatively Receives: Drug: Fentanyl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Postoperative pain
Pain at swallowing (numeric rating scale (NRS) 0-10, lower scores are better outcomes)
Measured: On arrival at the post-anesthesia care unit
Opioid consumption
Cumulative postoperative opioid consumption in morphine equivalents
Measured: First 5 postoperative days
Secondary outcomes (4)
Postoperative pain
Pain at swallowing (numeric rating scale (NRS) 0-10, lower scores are better outcomes)
Measured: 1, 2, 3, 5 and 7 days after surgery
Opioid consumption
Cumulative postoperative opioid consumption in morphine equivalents
Measured: 1 and 7 days after surgery
Postoperative nausea and vomiting (none, mild, moderate, severe)
Nausea and/or vomiting (PONV), proportion of patients with none or mild PONV
Measured: 1, 2 and 3 days after surgery
Sedation
Level of sedation (Ramsay Scale (1-4)), proportion of patients being co-operative, oriented and tranquil
Measured: 4 hours after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2022
- Study start28 Nov 2022
- Primary completionJan 2024 (estimated)
- Study completionAug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Postoperative PainStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lone Nikolajsen, PhD, DMSc, Study chair, Aarhus University Hospital, Department of Anesthesia and Intensive Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05445856
- Sponsor's protocol ID
- 2022-002496-11
- Acronym
- METATONS
- Status last verified
- Dec 2023
- First submitted
- 30 Jun 2022
- Last updated
- 5 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: IPD will be shared upon reasonable request
Publications
Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Vender JS, Benson J, Newmark RL. Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Anesthesiology. 2017 May;126(5):822-833. doi: 10.1097/ALN.0000000000001609.
PubMed 28418966Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633.
PubMed 25837528Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
PubMed 20418538Udelsmann A, Maciel FG, Servian DC, Reis E, de Azevedo TM, Melo Mde S. Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting. Rev Bras Anestesiol. 2011 Nov-Dec;61(6):695-701. doi: 10.1016/S0034-7094(11)70078-2. English, Multiple languages.
PubMed 22063370Bondergaard M, Uhrbrand PG, Karaca T, Rhode M, Kjaergaard T, Svendsen RT, Klug TE, Nikolajsen L, Friesgaard KD. Intraoperative methadone for postoperative pain in adult patients undergoing tonsillectomy-a randomised controlled trial. BJA Open. 2025 May 26;14:100418. doi: 10.1016/j.bjao.2025.100418. eCollection 2025 Jun.
PubMed 40502985
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intraoperative Methadone for Postoperative Pain in Patients Undergoing Tonsillectomy - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05445856
- Acronym / sponsor ID
- METATONS / 2022-002496-11
- Conditions
- Postoperative Pain
- Keywords
- Postoperative pain, Methadone
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- 28 Nov 2022 (actual)
- Primary completion
- Jan 2024 (estimated)
- Study completion
- Aug 2024 (estimated)
- First posted
- 6 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A randomized controlled trial evaluating the efficacy and safety of single-shot intraoperative methadone for postoperative pain in patients undergoing tonsillectomy. Fentanyl is used as an active comparator
Detailed description
This study is an investigator-initiated, prospective, randomised controlled trial with two arms: an intervention arm (methadone) and a control arm (fentanyl). Patients scheduled for tonsillectomy at Randers Regional Hospital, Denmark, will be approached for study participation.
Patients are randomised in a 1:1 ratio in blocks of varying sizes (between 4 and 8) to receive either intraoperative methadone or fentanyl. The randomisation assignment will be handled by the hospital pharmacy using a web-based central randomisation procedure (www.sealedenvelope.com).
The study drug will be prepared by the hospital pharmacy at Aarhus University Hospital and delivered as kits with identical appearance, marked with the randomization number (1-130). On the day of surgery, a kit will be opened and a 10 ml syringe with study drug (methadone 2 mg/ml or fentanyl 30 microgram/ml or ) will prepared by a health care professional (nurse or medical doctor not involved in the study or the treatment of patients). Once prepared, the blinded study drug will be given to and handled by one of the research team members and administered after induction of anesthesia and prior to surgery
The dose of the study drug will be administered as intravenous bolus dose in equipotent doses (0.2 mg/kg / 3 μg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (women: height (cm) - 105. Men: height (cm) - 100)) after induction of anaesthesia and before the start of surgery.
Postoperative data will be obtained by reviewing hospital records, by interview and electronic questionnaires sent by email.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methadone | Experimental | Drug: MethadoneSingle-shot intravenous methadone 0.2 mg/kg administered intraoperatively |
| Fentanyl | Active comparator | Drug: FentanylSingle-shot intravenous fentanyl 3 microgram/kg administered intraoperatively |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- All patients (≥18 years) scheduled for elective tonsillectomy
Key exclusion criteria (15 listed)
- American Society of Anaesthesiologists (ASA) physical status IV or V
- Allergy to study drugs
- Daily use of opioids 7 days prior to surgery
- Inability to provide informed consent
- Severe respiratory insufficiency
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MethadoneMethadone is administered as a single intravenous dose after induction of anesthesia and prior to initiation of surgery | Drug | Methadone |
| FentanylFentanyl is administered as a single intravenous dose after induction of anesthesia and prior to initiation of surgery | Drug | Fentanyl |
Primary outcome
Postoperative pain
Time frame: On arrival at the post-anesthesia care unit
Pain at swallowing (numeric rating scale (NRS) 0-10, lower scores are better outcomes)
Opioid consumption
Time frame: First 5 postoperative days
Cumulative postoperative opioid consumption in morphine equivalents
4 secondary outcomes
Postoperative pain
Time frame: 1, 2, 3, 5 and 7 days after surgery
Opioid consumption
Time frame: 1 and 7 days after surgery
Postoperative nausea and vomiting (none, mild, moderate, severe)
Time frame: 1, 2 and 3 days after surgery
Sedation
Time frame: 4 hours after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2023.
- Background: PubMed 28418966Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Vender JS, Benson J, Newmark RL. Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Anesthesiology. 2017 May;126(5):822-833. doi: 10.1097/ALN.0000000000001609.
- Background: PubMed 25837528Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633.
- Background: PubMed 20418538Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24.
- Background: PubMed 22063370Udelsmann A, Maciel FG, Servian DC, Reis E, de Azevedo TM, Melo Mde S. Methadone and morphine during anesthesia induction for cardiac surgery. Repercussion in postoperative analgesia and prevalence of nausea and vomiting. Rev Bras Anestesiol. 2011 Nov-Dec;61(6):695-701. doi: 10.1016/S0034-7094(11)70078-2. English, Multiple languages.
- Derived from this study: PubMed 40502985Bondergaard M, Uhrbrand PG, Karaca T, Rhode M, Kjaergaard T, Svendsen RT, Klug TE, Nikolajsen L, Friesgaard KD. Intraoperative methadone for postoperative pain in adult patients undergoing tonsillectomy-a randomised controlled trial. BJA Open. 2025 May 26;14:100418. doi: 10.1016/j.bjao.2025.100418. eCollection 2025 Jun.
- Individual participant dataSharing planned: Undecided. IPD will be shared upon reasonable request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lone Nikolajsen, PhD, DMSc study chair
Aarhus University Hospital, Department of Anesthesia and Intensive Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Methadone and Fentanyl in people with Postoperative Pain, run by University of Aarhus at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Michael Bøndergaard, MD (004578420510, michael.vinther@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Postoperative pain (time frame: On arrival at the post-anesthesia care unit). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05445856, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2023.