MethadonePhase 4NCT05581901
Perioperative Methadone in Hip Fracture Patients
A Phase 4 study testing Methadone (Dose1), Methadone (Dose 2) and Methadone (Dose 3) in people with Methadone and Pain, Post Operative, run by University of Southern Denmark at 1 site in Denmark.
Trial summary
Postoperative analgesic treatment needs to be improved. Numerous studies suggest that a single dose of Methadone given during surgery significantly ameliorates postoperative pain and reduces postoperative opioid consumption. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Methadone, Pain, Post Operative, Pain, Postoperative
- What is being tested?
- Methadone (Dose1), Methadone (Dose 2) and Methadone (Dose 3)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteDenmark
- Study dates
- 12 Jan 2023to 4 Apr 2023
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients diagnosed with a hip fracture on x-rays (collum femoris fractures, pertrochanteric fractures and subtrochanteric fractures).
- Patients must be able to reliably assess their level of pain using the VRS and be able to ask for supplementary analgesics if needed.
- Patients must understand the information given and be able to read and speak Danish.
- Patients must be able to give informed consent.
Who cannot join
- Polytrauma (defined as a trauma with one or more absolute indications for surgical intervention).
- Previous allergic reactions or hypersensitivity towards Methadone hydrochloride or Sodium-chloride.
- Health conditions preventing treatment, i.e. chronic obstructive pulmonary disease (Gold classification C+D), history with acute asthma attacks or atopic skin conditions, cor pulmonale, raised intracranial pressure or head injury, Pheochromocytoma, history with paralytic ileus, QT interval prolongation, myasthenia gravis, liver disorders or hypotension.
- Concurrent administration with monoamine oxidase inhibitors or within 2 weeks of suspending treatment with these medicinal products.
- Concurrent administration of sedatives, e.g. Benzodiazepines or related drugs.
- Included in other studies (e.g., SENSE-trial).
- Known cognitive disorders e.g., dementia.
- Current drug addiction e.g., opioid addiction or intravenous addiction.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Perioperative Methadone for Ameliorating Postoperative Pain and Reduction in Postoperative Opioid Consumption in Hip Fracture Patients - Dosage Adjusting Pilot-study
Postoperative analgesic treatment needs to be improved. Numerous studies suggest that a single dose of Methadone given during surgery significantly ameliorates postoperative pain and reduces postoperative opioid consumption. Perioperative methadone is already used in isolated cases such as patients with chronic pain or patients with high morphine tolerance. However, it is not routinely used in the elderly and fragile, and there is insufficient reliable evidence on this treatment and population. Further investigation is highly relevant and necessary.
Read the detailed description
A multimodal approach and the use of peripheral nerve blocks have improved the treatment of postoperative pain. However, supplemental opioids are predominantly necessary and often continued for months or years after surgery. In fact, continued use of opioids after surgery is an increasing challenge. Consequently, patients undergoing surgery are at risk of experiencing side effects and developing physical as well as psychological addiction to opioids. The most common opioid-related side effects include obstipation, nausea, itchy skin, dry mouth, vertigo, and sedation. The means to decrease the need for opioids in the postoperative phase are in high demand, and therefore the investigation of perioperative Methadone is highly relevant. Methadone is a lipophilic opioid agonist with a large distribution volume and a very long elimination half-life of 15 - 60 hours. It is also an N-methyl D-aspartate (NMDA) receptor antagonist, which attenuates opioid-induced tolerance and hyperalgesia. Furthermore, Methadone inhibits the reuptake of Serotonin and Noradrenalin, which could positively affect the experience of pain in the postoperative phase. Methadone is mostly excreted through the bile and can, therefore, even be used in patients with reduced kidney function. Methadone's analgesic effects occur only eight minutes after intravenous administration. In most studies, methadone is given perioperatively in dosages of 0.10-0.30 mg/kg and is commenced at the induction of anaesthesia or the initiation of surgery. Studies investigating the optimal dosage and time for administration found that patients receiving methadone after the procedure needed twice as much opioid pain medication on postoperative day one compared to patients receiving methadone at anaesthetic induction. These studies also indicate that using smaller dosages such as 5-10 mg, the analgesic duration is only 3-4 hours, whereas doses of 20 mg or more have a clinical effect closely related to the elimination half-life of 15-60 hours without any increased risk for respiratory depression. The aim of this study is to determine the optimal dose of methadone for a future randomized controlled trial (RCT). The objective is to investigate whether doses greater than 0.10 mg/kg are tolerated with no increased risk to respiratory depression, side effects, or prolonged stay in the post-anaesthesia care units (PACU).
- Being tested
- Methadone (Dose1), Methadone (Dose 2), Methadone (Dose 3)
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methadone (Dose1)Drug
Also called Dose 1
Dose: 0.10mg/kg
Methadone (Dose 2)Drug
Also called Dose 2
Dose: 0.15mg/kg
Methadone (Dose 3)Drug
Also called Dose 3
Dose 0.20mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Methadone (Dose 1) | Experimental | Methadone will be administered intravenously at the beginning of surgery, and will only be administered this one time. The gradual upward titration of Methadone will be managed using adaptive platform design. This way the number of patients in each group will be determined by the adaptive platform algorithm. Receives: Drug: Methadone (Dose1) |
| Methadone (Dose 2) | Experimental | Methadone will be administered intravenously at the beginning of surgery, and will only be administered this one time. The gradual upward titration of Methadone will be managed using adaptive platform design. This way the number of patients in each group will be determined by the adaptive platform algorithm. Receives: Drug: Methadone (Dose 2) |
| Methadone (Dose 3) | Experimental | Methadone will be administered intravenously at the beginning of surgery, and will only be administered this one time. The gradual upward titration of Methadone will be managed using adaptive platform design. This way the number of patients in each group will be determined by the adaptive platform algorithm. Receives: Drug: Methadone (Dose 3) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Respiratory depression
Occurrence of a respiratory frequency <10/min and oxygen saturation <94 % despite 4 liters of oxygen/min.
Measured: 6 hours after surgery
Respiratory depression
Occurrence of a respiratory frequency <10/min and oxygen saturation <94 % despite 4 liters of oxygen/min.
Measured: 24 hours after surgery
Respiratory depression
Occurrence of a respiratory frequency <10/min and oxygen saturation <94 % despite 4 liters of oxygen/min.
Measured: 72 hours after surgery
Secondary outcomes (5)
Length of stay at the post anaesthetic care unit
Hours
Measured: up to 12 hours after surgery
Number of times Naloxone was administered
Numerical
Measured: immediately after the surgery (6, 24, 72 hours)
Postoperative opioid consumption
mean consumption of rescue medication
Measured: immediately after the surgery (6, 24, 72 hours)
Opioid-related side-effects
Opioid-related side-effects will be registered binomial as nausea and vomiting
Measured: immediately after the surgery (6, 24 hours)
Postoperative pain
Patients will be asked to assess pain intensity at the time of arrival from the post-anaesthesia care unit using the Verbal Rating Scale (VRS) consisting of 6 categories where 0 is no pain and 5 is the highest level of pain (worst outcome).
Measured: immediately after the surgery (0, 6, 24, 72 hours)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2022
- Study start12 Jan 2023
- Primary completion23 Mar 2023
- Study completion4 Apr 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MethadoneStudies of the same condition, open and under way.
- More trials run by University of Southern DenmarkThe 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern Denmark
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jesper Schønnemann, Principal investigator, Hospital of Southern Denmark - Aabenraa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05581901
- Sponsor's protocol ID
- SHS-An-2-2022
- Status last verified
- Apr 2023
- First submitted
- 15 Sep 2022
- Last updated
- 18 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pedersen AK, Nygaard KH, Petersen SR, Specht K, Strom T, Moos CM, Skjot-Arkil H, Schonnemann JO. Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) - A statistical analysis plan for an adaptive dose-finding trial. Contemp Clin Trials Commun. 2023 Nov 14;36:101228. doi: 10.1016/j.conctc.2023.101228. eCollection 2023 Dec.
PubMed 38047142
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Methadone for Ameliorating Postoperative Pain and Reduction in Postoperative Opioid Consumption in Hip Fracture Patients - Dosage Adjusting Pilot-study
- ClinicalTrials.gov ID
- NCT05581901
- Acronym / sponsor ID
- SHS-An-2-2022
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of Southern DenmarkUniversity, hospital or other
- Study start
- 12 Jan 2023 (actual)
- Primary completion
- 23 Mar 2023 (actual)
- Study completion
- 4 Apr 2023 (actual)
- First posted
- 17 Oct 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.
Postoperative analgesic treatment needs to be improved. Numerous studies suggest that a single dose of Methadone given during surgery significantly ameliorates postoperative pain and reduces postoperative opioid consumption. Perioperative methadone is already used in isolated cases such as patients with chronic pain or patients with high morphine tolerance. However, it is not routinely used in the elderly and fragile, and there is insufficient reliable evidence on this treatment and population. Further investigation is highly relevant and necessary.
Detailed description
A multimodal approach and the use of peripheral nerve blocks have improved the treatment of postoperative pain. However, supplemental opioids are predominantly necessary and often continued for months or years after surgery. In fact, continued use of opioids after surgery is an increasing challenge. Consequently, patients undergoing surgery are at risk of experiencing side effects and developing physical as well as psychological addiction to opioids. The most common opioid-related side effects include obstipation, nausea, itchy skin, dry mouth, vertigo, and sedation. The means to decrease the need for opioids in the postoperative phase are in high demand, and therefore the investigation of perioperative Methadone is highly relevant. Methadone is a lipophilic opioid agonist with a large distribution volume and a very long elimination half-life of 15 - 60 hours. It is also an N-methyl D-aspartate (NMDA) receptor antagonist, which attenuates opioid-induced tolerance and hyperalgesia. Furthermore, Methadone inhibits the reuptake of Serotonin and Noradrenalin, which could positively affect the experience of pain in the postoperative phase. Methadone is mostly excreted through the bile and can, therefore, even be used in patients with reduced kidney function. Methadone's analgesic effects occur only eight minutes after intravenous administration. In most studies, methadone is given perioperatively in dosages of 0.10-0.30 mg/kg and is commenced at the induction of anaesthesia or the initiation of surgery. Studies investigating the optimal dosage and time for administration found that patients receiving methadone after the procedure needed twice as much opioid pain medication on postoperative day one compared to patients receiving methadone at anaesthetic induction. These studies also indicate that using smaller dosages such as 5-10 mg, the analgesic duration is only 3-4 hours, whereas doses of 20 mg or more have a clinical effect closely related to the elimination half-life of 15-60 hours without any increased risk for respiratory depression. The aim of this study is to determine the optimal dose of methadone for a future randomized controlled trial (RCT). The objective is to investigate whether doses greater than 0.10 mg/kg are tolerated with no increased risk to respiratory depression, side effects, or prolonged stay in the post-anaesthesia care units (PACU).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, care provider)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Methadone (Dose 1) | Experimental | Drug: Methadone (Dose1)Methadone will be administered intravenously at the beginning of surgery, and will only be administered this one time. The gradual upward titration of Methadone will be managed using adaptive platform design. This way the number of patients in each group will be determined by the adaptive platform algorithm. |
| Methadone (Dose 2) | Experimental | Drug: Methadone (Dose 2)Methadone will be administered intravenously at the beginning of surgery, and will only be administered this one time. The gradual upward titration of Methadone will be managed using adaptive platform design. This way the number of patients in each group will be determined by the adaptive platform algorithm. |
| Methadone (Dose 3) | Experimental | Drug: Methadone (Dose 3)Methadone will be administered intravenously at the beginning of surgery, and will only be administered this one time. The gradual upward titration of Methadone will be managed using adaptive platform design. This way the number of patients in each group will be determined by the adaptive platform algorithm. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients diagnosed with a hip fracture on x-rays (collum femoris fractures, pertrochanteric fractures and subtrochanteric fractures).
- Patients must be able to reliably assess their level of pain using the VRS and be able to ask for supplementary analgesics if needed.
- Patients must understand the information given and be able to read and speak Danish.
- Patients must be able to give informed consent.
Key exclusion criteria (8 listed)
- Polytrauma (defined as a trauma with one or more absolute indications for surgical intervention).
- Previous allergic reactions or hypersensitivity towards Methadone hydrochloride or Sodium-chloride.
- Health conditions preventing treatment, i.e. chronic obstructive pulmonary disease (Gold classification C+D), history with acute asthma attacks or atopic skin conditions, cor pulmonale, raised intracranial pressure or head injury, Pheochromocytoma, history with paralytic ileus, QT interval prolongation, myasthenia gravis, liver disorders or hypotension.
- Concurrent administration with monoamine oxidase inhibitors or within 2 weeks of suspending treatment with these medicinal products.
- Concurrent administration of sedatives, e.g. Benzodiazepines or related drugs.
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 |
|---|---|---|
| Methadone (Dose1)Also: Dose 1Dose: 0.10mg/kg | Drug | Methadone (Dose 1) |
| Methadone (Dose 2)Also: Dose 2Dose: 0.15mg/kg | Drug | Methadone (Dose 2) |
| Methadone (Dose 3)Also: Dose 3Dose 0.20mg/kg | Drug | Methadone (Dose 3) |
Primary outcome
Respiratory depression
Time frame: 6 hours after surgery
Occurrence of a respiratory frequency <10/min and oxygen saturation <94 % despite 4 liters of oxygen/min.
Respiratory depression
Time frame: 24 hours after surgery
Occurrence of a respiratory frequency <10/min and oxygen saturation <94 % despite 4 liters of oxygen/min.
Respiratory depression
Time frame: 72 hours after surgery
Occurrence of a respiratory frequency <10/min and oxygen saturation <94 % despite 4 liters of oxygen/min.
5 secondary outcomes
Length of stay at the post anaesthetic care unit
Time frame: up to 12 hours after surgery
Number of times Naloxone was administered
Time frame: immediately after the surgery (6, 24, 72 hours)
Postoperative opioid consumption
Time frame: immediately after the surgery (6, 24, 72 hours)
Opioid-related side-effects
Time frame: immediately after the surgery (6, 24 hours)
Postoperative pain
Time frame: immediately after the surgery (0, 6, 24, 72 hours)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2023.
- Derived from this study: PubMed 38047142Pedersen AK, Nygaard KH, Petersen SR, Specht K, Strom T, Moos CM, Skjot-Arkil H, Schonnemann JO. Adjusting perioperative methadone dose for elderly and fragile hip fracture patients (MetaHip-trial) - A statistical analysis plan for an adaptive dose-finding trial. Contemp Clin Trials Commun. 2023 Nov 14;36:101228. doi: 10.1016/j.conctc.2023.101228. eCollection 2023 Dec.
- Individual participant dataSharing planned: No
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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.
Jesper Schønnemann principal investigator
Hospital of Southern Denmark - Aabenraa
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 (Dose1), Methadone (Dose 2) and Methadone (Dose 3) in people with Methadone and Pain, Post Operative, run by University of Southern Denmark 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 4 inclusion and 8 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: finished, as of the sponsor's last update on 18 Apr 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory depression (time frame: 6 hours after surgery). The study lists 3 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 NCT05581901, which also lists 1 linked publication.
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 18 Apr 2023.