Hip FracturesPhase 4NCT06086171
Perioperative Methadone Compared to Placebo in Elderly Hip Fracture Patients
A Phase 4 study testing Methadone Hydrochloride in people with Hip Fractures and Methadone, run by University of Southern Denmark at 1 site in Denmark.
Trial summary
Hip fractures are associated with severe pain and are sustained by the elderly population. Demand for adequate pain relief combined with a low tolerance for analgesic drugs makes the treatment of elderly hip fracture patients difficult. Perioperative methadone could improve the analgesic treatment of these patients. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Hip Fractures, Methadone
- What is being tested?
- Methadone Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 129 participants
- Where
- 1 siteDenmark
- Study dates
- 10 Nov 2023to 21 Feb 2025
- 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 an acute hip fracture (incurred <24 hours ago) on x-rays in the emergency department (ED) at the university hospital of southern Denmark (SHS). This includes collum femoris fractures, pertrochanteric fractures, and subtrochanteric fractures.
- Patients must be able to read and understand Danish.
Who cannot join
- Multiple fractures or multi-trauma patient
- Previous allergic reactions or hypersensitivity towards methadone hydrochloride or sodium chloride
- Health conditions preventing treatment:
- Chronic obstructive pulmonary disease with either past exacerbations or daily symptoms History of acute asthma attacks History of drug-induced eczema Pulmonary hypertension Raised intracranial pressure or recent head injury Pheochromocytoma History of paralytic ileus QT-interval prolongation on electrocardiogram (ECG) Myasthenia gravis Known liver disorder Hypotension (systolic blood pressure <100 mmHg at admission) Acute pancreatitis Severe kidney disease (GFR ≤10)
- Concurrent administration with MAO inhibitors or within 2 weeks of suspending treatment with these medicinal products
- Concurrent administration of benzodiazepines
- Impaired cognitive function e.g. dementia. Patients must be able to give informed consent and be able to ask for rescue analgesics if needed
- Current opioid addiction or intravenous addiction
Trial locations and contacts
1 site in 1 country.
About this study
Hip fractures are associated with severe pain and are sustained by the elderly population. Demand for adequate pain relief combined with a low tolerance for analgesic drugs makes the treatment of elderly hip fracture patients difficult. Perioperative methadone could improve the analgesic treatment of these patients. An earlier pilot study showed that 0.10 mg/kg was safe to use. This study further investigates the advantages of methadone. The study's objective is to investigate the analgesic effects of a single dose of methadone given during hip fracture surgery.
Read the detailed description
Studies investigating the perioperative use of methadone have shown promising analgesic properties. Our pilot study (EudraCT no.: 2022-001857-22) showed that a dosage of 0.10 mg/kg was safe to use and showed excellent analgesic properties. Sufficient management of acute postoperative pain is important in relation to morbidity, hospital costs, and mortality. About 60% of patients undergoing surgical intervention experience moderate to severe postoperative pain. Thus, sufficient analgesic treatment is crucial in the initial postoperative days, which are considered the most painful phase of recovery. Opioids have conventionally been used as an analgesic treatment in this phase. However, this treatment has been accompanied by side effects and addiction. Methadone shares these side effects, however, as methadone only needs to be administered once, the risk of side effects decreases significantly. This study will investigate the analgesic effects of a single dose of methadone given during hip fracture surgery.
The first objective is to investigate the analgesic effect of perioperative methadone compared with a placebo in acute hip fracture surgery. The second objective is to investigate the long-term effects of methadone on continued opioid consumption, pain, and mobility three months after surgery.
The null hypothesis is that there is no difference in postoperative pain, opioid consumption, or related side effects if a patient receives a dose of methadone or placebo during the surgery.
- Conditions
- Hip Fractures, Methadone
- Being tested
- Methadone Hydrochloride, Placebo
- Keywords
- Hip fractures, Elderly, Fragile, methadone, perioperative, analgesic treatment, pain, verbal rating scale, morphine consumption
- Medical subject headings
- Hip Fractures, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Methadone HydrochlorideDrug
Also called Methadone
Methadone hydrochloride (0.10 mg/kg) administered intravenously at the induction of anaesthesia
PlaceboOther
Also called Saline
Saline solution
| Study group | Role | What they receive |
|---|---|---|
| Methadone | Experimental | Methadone hydrochloride (0.10 mg/kg) administered intravenously at the induction of anaesthesia Receives: Drug: Methadone Hydrochloride |
| Placebo | Placebo comparator | Standard saline solution administered intravenously at the induction of anaesthesia Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Consumption of daily morphine equivalents 3 days post operatively
All opioids (short-acting and long-acting) will be converted into daily morphine milligram equivalent doses. The amount of opioids used by the patient within the last 24 hours will be registered daily. A minimum amount of 0 mg and a maximum amount of 150 mg can be recorded.
Measured: 3 days post-surgery
Consumption of daily morphine equivalents 3 months post operatively
The opioid consumption will be registered as a mean daily consumption of both long-acting opioids and rescue medication prescribed in the medication chart and reported by the patient. Different types of opioids will be converted into the daily morphine milligram equivalent dose. Minimum score will be 0 mg and the maximum will be 150 mg.
Measured: 3 months post-surgery
Secondary outcomes (12)
Postoperative pain assessment with verbal rating scale (VRS)
Patients will be asked to assess pain intensity daily in the hip both at rest and when mobilized. Pain intensity will be evaluated using the verbal rating scale consisting of five choices - 1 (No pain), 2 (Slight pain), 3 (Moderate pain), 4 (Severe pain), and 5 (Unbearable pain).
Measured: 3 days post-surgery
Time until patient first stands up post-surgery
This will be registered in hours and minutes. The minimum is 0 hours and 0 minutes and the maximum is 72 hours and 0 minutes.
Measured: up to 72 hours post-surgery
Mobility assessment using the Cumulated Ambulation Score (CAS)
The cumulated ambulation score describes the patient's independence with regard to three activities. The first getting in and out of bed, the second ability to transition from sit-to-stand-to-sit from a chair, and the third is walking ability. Each of these activities is assessed on a three-point scale from 0-2 (0 = Not able to, despite human assistance and verbal cueing, 1 = Able to, with human assistance and/or verbal cueing from one or more persons, 2 = Able to safely, without human assistance or verbal cueing. A CAS score will range from zero (worst) to six (best) and will be measure daily.
Measured: 3 days post-surgery
Number of patients with post operative nausea or vomiting (PONV)
Postoperative nausea or vomiting (PONV) will be registered binomial as "yes" or "no" once daily
Measured: 3 days post-surgery
Number of days to discharge after surgery
The number of days from ward admission until discharge. Patients moved to another department are still considered hospitalized. The minimum is 0 days and the maximum is 14 days.
Measured: From admission to the ward to discharge, up to 14 days
Number of patients requiring an antidote
Administration of an antidote will be registered binomial as "yes" or "no". Indications for the use of an antidote include a respiratory frequency of <10/min with peripheral oxygenation of <94% despite 4 liters of oxygen/minute, clinical signs of opioid overdose e.g. disproportionate drowsiness, or if the orthopaedic resident deems it necessary.
Measured: 3 days post-surgery
Number of patients with delirium assessed using the Confusion Assessment Method (CAM)
Patients will be monitored using the confusion assessment method for signs of delirium. The method is binomial so that 0 means no signs of delirium and 1 means a patient is delirious.
Measured: 3 days post-surgery
Number of participants with constipation
Occurrence of constipation during admission will be registered binomial as "yes" or "no". A patient with no bowel movements for ≥2 days is considered constipated.
Measured: 3 days post-surgery
Postoperative pain assessment with verbal rating scale (VRS)
Patients will be asked to assess pain intensity daily in the hip both at rest and when mobilized. Pain intensity will be evaluated using the verbal rating scale consisting of five choices - 1 (No pain), 2 (Slight pain), 3 (Moderate pain), 4 (Severe pain), and 5 (Unbearable pain).
Measured: 3 months post-surgery
Quality of life assessed using EQ-5D-5L questionnaire
The questionnaire comprises of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
Measured: 3 months post-surgery
Patient mobility assessed using the new mobility score (NMS)
New mobility score assesses gait; inside the home, outside the home and whilst shopping. A score of 0-3 points is given for each of these three functions, resulting in a total score between 0-9 points.
Measured: 3 months post-surgery
Number of persistent side effects
The persistent presence of potential adverse reactions will be registered. This includes disproportional dizziness, vertigo, nausea, vomiting, constipation, and drowsiness.
Measured: 3 months post-surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2023
- Study start10 Nov 2023
- Primary completion29 Oct 2024
- Study completion21 Feb 2025
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 Hip FracturesStudies 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern Denmark
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jesper Ougaard Schønnemann, Study director, Sygehus Sønderjylland (Region Syddanmark)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06086171
- Sponsor's protocol ID
- SHS-An-4-2023
- Status last verified
- Mar 2025
- First submitted
- 4 Oct 2023
- Last updated
- 18 Mar 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nygaard KH, Strom T, Specht K, Petersen SR, Schonnemann JO. Perioperative methadone compared to placebo in elderly hip fracture patients: a study protocol for a randomized controlled trial (MetaHip trial). Trials. 2024 Dec 20;25(1):842. doi: 10.1186/s13063-024-08694-6.
PubMed 39707407
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Perioperative Methadone Compared to Placebo in Elderly Hip Fracture Patients
- ClinicalTrials.gov ID
- NCT06086171
- Acronym / sponsor ID
- SHS-An-4-2023
- Conditions
- Hip Fractures, Methadone
- Keywords
- Hip fractures, Elderly, Fragile, methadone, perioperative, analgesic treatment, pain, verbal rating scale
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- University of Southern DenmarkUniversity, hospital or other
- Study start
- 10 Nov 2023 (actual)
- Primary completion
- 29 Oct 2024 (actual)
- Study completion
- 21 Feb 2025 (actual)
- First posted
- 17 Oct 2023 (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.
Hip fractures are associated with severe pain and are sustained by the elderly population. Demand for adequate pain relief combined with a low tolerance for analgesic drugs makes the treatment of elderly hip fracture patients difficult. Perioperative methadone could improve the analgesic treatment of these patients. An earlier pilot study showed that 0.10 mg/kg was safe to use. This study further investigates the advantages of methadone. The study's objective is to investigate the analgesic effects of a single dose of methadone given during hip fracture surgery.
Detailed description
Studies investigating the perioperative use of methadone have shown promising analgesic properties. Our pilot study (EudraCT no.: 2022-001857-22) showed that a dosage of 0.10 mg/kg was safe to use and showed excellent analgesic properties. Sufficient management of acute postoperative pain is important in relation to morbidity, hospital costs, and mortality. About 60% of patients undergoing surgical intervention experience moderate to severe postoperative pain. Thus, sufficient analgesic treatment is crucial in the initial postoperative days, which are considered the most painful phase of recovery. Opioids have conventionally been used as an analgesic treatment in this phase. However, this treatment has been accompanied by side effects and addiction. Methadone shares these side effects, however, as methadone only needs to be administered once, the risk of side effects decreases significantly. This study will investigate the analgesic effects of a single dose of methadone given during hip fracture surgery.
The first objective is to investigate the analgesic effect of perioperative methadone compared with a placebo in acute hip fracture surgery. The second objective is to investigate the long-term effects of methadone on continued opioid consumption, pain, and mobility three months after surgery.
The null hypothesis is that there is no difference in postoperative pain, opioid consumption, or related side effects if a patient receives a dose of methadone or placebo during the surgery.
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: Methadone HydrochlorideMethadone hydrochloride (0.10 mg/kg) administered intravenously at the induction of anaesthesia |
| Placebo | Placebo comparator | Other: PlaceboStandard saline solution administered intravenously at the induction of anaesthesia |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients diagnosed with an acute hip fracture (incurred <24 hours ago) on x-rays in the emergency department (ED) at the university hospital of southern Denmark (SHS). This includes collum femoris fractures, pertrochanteric fractures, and subtrochanteric fractures.
- Patients must be able to read and understand Danish.
Key exclusion criteria (8 listed)
- Multiple fractures or multi-trauma patient
- Previous allergic reactions or hypersensitivity towards methadone hydrochloride or sodium chloride
- Health conditions preventing treatment:
- Chronic obstructive pulmonary disease with either past exacerbations or daily symptoms History of acute asthma attacks History of drug-induced eczema Pulmonary hypertension Raised intracranial pressure or recent head injury Pheochromocytoma History of paralytic ileus QT-interval prolongation on electrocardiogram (ECG) Myasthenia gravis Known liver disorder Hypotension (systolic blood pressure <100 mmHg at admission) Acute pancreatitis Severe kidney disease (GFR ≤10)
- Concurrent administration with MAO inhibitors or within 2 weeks of suspending treatment with these medicinal products
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 HydrochlorideAlso: MethadoneMethadone hydrochloride (0.10 mg/kg) administered intravenously at the induction of anaesthesia | Drug | Methadone |
| PlaceboAlso: SalineSaline solution | Other | Placebo |
Primary outcome
Consumption of daily morphine equivalents 3 days post operatively
Time frame: 3 days post-surgery
All opioids (short-acting and long-acting) will be converted into daily morphine milligram equivalent doses. The amount of opioids used by the patient within the last 24 hours will be registered daily. A minimum amount of 0 mg and a maximum amount of 150 mg can be recorded.
Consumption of daily morphine equivalents 3 months post operatively
Time frame: 3 months post-surgery
The opioid consumption will be registered as a mean daily consumption of both long-acting opioids and rescue medication prescribed in the medication chart and reported by the patient. Different types of opioids will be converted into the daily morphine milligram equivalent dose. Minimum score will be 0 mg and the maximum will be 150 mg.
12 secondary outcomes
Postoperative pain assessment with verbal rating scale (VRS)
Time frame: 3 days post-surgery
Time until patient first stands up post-surgery
Time frame: up to 72 hours post-surgery
Mobility assessment using the Cumulated Ambulation Score (CAS)
Time frame: 3 days post-surgery
Number of patients with post operative nausea or vomiting (PONV)
Time frame: 3 days post-surgery
Number of days to discharge after surgery
Time frame: From admission to the ward to discharge, up to 14 days
Number of patients requiring an antidote
Time frame: 3 days post-surgery
Number of patients with delirium assessed using the Confusion Assessment Method (CAM)
Time frame: 3 days post-surgery
Number of participants with constipation
Time frame: 3 days post-surgery
Postoperative pain assessment with verbal rating scale (VRS)
Time frame: 3 months post-surgery
Quality of life assessed using EQ-5D-5L questionnaire
Time frame: 3 months post-surgery
Patient mobility assessed using the new mobility score (NMS)
Time frame: 3 months post-surgery
Number of persistent side effects
Time frame: 3 months post-surgery
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 Mar 2025.
- Derived from this study: PubMed 39707407Nygaard KH, Strom T, Specht K, Petersen SR, Schonnemann JO. Perioperative methadone compared to placebo in elderly hip fracture patients: a study protocol for a randomized controlled trial (MetaHip trial). Trials. 2024 Dec 20;25(1):842. doi: 10.1186/s13063-024-08694-6.
- 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 Ougaard Schønnemann study director
Sygehus Sønderjylland (Region Syddanmark)
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 Hydrochloride in people with Hip Fractures and Methadone, 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 2 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 Mar 2025. 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. Some participants in this study may receive a placebo. 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?
Consumption of daily morphine equivalents 3 days post operatively (time frame: 3 days post-surgery). 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 NCT06086171, 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 Mar 2025.