Clinical trial NCT06086171: Perioperative Methadone Compared to Placebo in Elderly Hip Fracture Patients
Official title: Perioperative Methadone Compared to Placebo in Elderly Hip Fracture Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hip Fractures
Methadone
Keywords: Hip fractures
Elderly
Fragile
methadone
perioperative
analgesic treatment
pain
verbal rating scale
morphine consumption
Lead sponsor: University of Southern Denmark
Sponsor class: OTHER
First posted: 2023-10-17
Enrollment: 129
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Consumption of daily morphine equivalents 3 days post operatively
timeFrame: 3 days post-surgery
measure: Consumption of daily morphine equivalents 3 months post operatively
timeFrame: 3 months post-surgery
Secondary outcomes:
measure: Postoperative pain assessment with verbal rating scale (VRS)
timeFrame: 3 days post-surgery
measure: Time until patient first stands up post-surgery
timeFrame: up to 72 hours post-surgery
measure: Mobility assessment using the Cumulated Ambulation Score (CAS)
timeFrame: 3 days post-surgery
measure: Number of patients with post operative nausea or vomiting (PONV)
timeFrame: 3 days post-surgery
measure: Number of days to discharge after surgery
timeFrame: From admission to the ward to discharge, up to 14 days
measure: Number of patients requiring an antidote
timeFrame: 3 days post-surgery
measure: Number of patients with delirium assessed using the Confusion Assessment Method (CAM)
timeFrame: 3 days post-surgery
measure: Number of participants with constipation
timeFrame: 3 days post-surgery
measure: Postoperative pain assessment with verbal rating scale (VRS)
timeFrame: 3 months post-surgery
measure: Quality of life assessed using EQ-5D-5L questionnaire
timeFrame: 3 months post-surgery
measure: Patient mobility assessed using the new mobility score (NMS)
timeFrame: 3 months post-surgery
measure: Number of persistent side effects
timeFrame: 3 months post-surgery
Other outcomes:
Locations:
city: Aabenraa
country: Denmark
facility: Sygehus Sønderjylland
state: Southern Denmark
Study officials:
affiliation: Sygehus Sønderjylland (Region Syddanmark)
name: Jesper Ougaard Schønnemann
role: STUDY_DIRECTOR
References: