Clinical trial NCT06212622: Is the Rate of Early Mobilisation in Hip Fracture Patients Using Alfentanil Better Than Standard Opioid Analgesia?
Official title: Is the Rate of Early Mobilisation in Hip Fracture Patients Using Alfentanil Better Than Standard Opioid Analgesia (REHAB): a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hip Injuries
Hip Fractures
Pain
Post Operative Pain
Early Ambulation
Keywords: early mobilisation
hip fracture
pain
oxycodone
alfentanil
ambulation
Lead sponsor: NHS Lothian
Sponsor class: OTHER_GOV
First posted: 2024-01-19
Enrollment: 64
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants listed for urgent hip fracture surgery, after sustaining a hip fracture surgery under the care of participating surgeons at the institution of RIE. 64 participants will be included in this prospective cohort study, 32 in each cohort. There will be consecutively recruitment and follow all hip fracture patients admitted over a month at RIE.

Brief summary: Hip fracture injuries are linked with increased morbidity, frailty, and mortality risk. Studies have shown that in hip fracture surgery, early mobilisation confers better pain control, 30-day complication and mortality rates and could reduce in hospital length of stay.

Though early mobilisation may provide numerous post operative benefits, there are barriers to achieving this reliably and effectively. One such difficulty is pain.

In the Royal Infirmary of Edinburgh (RIE) like many boards across Scotland, oral oxycodone has been routinely used as analgesia to help with post operative pain, in patients who have undergone orthopaedic trauma injuries. However, this analgesic modality is utilised to help with general post operative pain, rather than targeted abolition of pain prior to physiotherapy.

Alfentanil is a relatively new medication which has a very rapid onset of action and short half life. Alfentanil may prove to be a superior form of analgesia for the purpose of encouraging early mobilisation after hip fracture surgery. This study could provide robust evidence for regular use of alfentanil prior to physiotherapy in early post operative hip fracture surgery patients.

Detailed description: Hip fractures are amongst the most common orthopaedic injuries. These fractures predominantly occur in the elderly population, secondary to osteoporosis. Projection studies from across the world suggest that incidence rates of hip fractures are set to increase. Worldwide projections indicate that hip fracture cases will double from 1.26 million in 1990, to 2.6 million by 2025, and to 4.5 million by 2050. The National Joint Registry reports that the number of hip fractures have increased from 1,371 in 2010 to 84,998 in 2021 across England, Wales and Northern Ireland. The Scottish Hip Fracture Audit identifies an increase from 6,369 hip fracture cases in 2007 to 8,380 in 2022. Given the exponential rise in the frail elderly population, these numbers will only further rise in the future.

Hip fracture injuries are linked with increased morbidity, frailty, and mortality risk. Moreover, there is significant social and economic costs on the healthcare system stemming from these injuries. In the United States, these costs are greater than $5.96 billion, annually. In the United Kingdom, these costs are approximately £1.1 billion. Healthcare systems globally, are becoming progressively more financially restrained, and the incidence of hip fractures are set to increase. Thus, further emphasis should be placed on interventions to reduce morbidity and mortality in this frail elderly patient group.

Many studies have shown that early mobilisation after hip fracture surgery provides reduced post operative pain and complication rates and reduces length of stay (LOS) in hospital. Some studies have demonstrated that early ambulation reduces 30-day mortality rates in this patient population. It has been demonstrated that early mobilisation was also associated with an increased rate of discharges directly home, compared to those patients who mobilised late. Although elderly patients have associated co-morbidity and a higher risk of delirium, neither factors influenced inability to mobilise early after surgery. They also found that a greater number of patients who mobilised early were able to be discharged directly home.

Though early mobilisation may provide numerous post operative benefits, there are barriers to achieving this reliably and effectively. One such difficulty is pain. Studies report that pain is often a key obstacle to early ambulation after surgery. In the Royal Infirmary of Edinburgh (RIE) like many boards across Scotland, oral oxycodone has been routinely used as analgesia to help with post operative pain, in patients who have undergone orthopaedic trauma injuries. However, this analgesic modality is utilised to help with general post operative pain, rather than targeted abolition of pain prior to physiotherapy.

Oxycodone has been utilised in clinical practice since 1917. There is in depth literature on the pharmacokinetics of oxycodone. The onset of action of oral oxycodone is between 10-30 minutes. Peak onset occurs around 1 hour. Plasma half-life is 3-5 hours, regardless of route of administration.

On the other hand, alfentanil is relatively new, and the literature is scarce on its pharmacokinetic properties. There is consensus amongst the literature that onset of action of alfentanil is very rapid, with peak onset of intravenous alfentanil as quick as 2 minutes. Plasma half-life of oral alfentanil is 1-2 hours. Moreover, side effects of respiratory depression are lower than that from fentanyl or sufentanil. The combination of rapid onset of pain relief, with an equally quick excretion, makes this medication appealing in palliative care medicine, in which patients are typically frail. This is particularly the case in patients with renal impairment since this medication is excreted by the liver.

Alfentanil may prove to be a superior form of analgesia for the purpose of encouraging early mobilisation after hip fracture surgery.

Eligibility criteria: Inclusion Criteria:

* Listed for urgent hip fracture surgery - dynamic hip screw/cannulated hip screw/hemiarthroplasty/total hip arthroplasty/intramedullary nail
* Sustained an insufficiency/low energy type hip fracture
* Male or female aged over 60
* Able to provide informed consent

Exclusion Criteria:

* Pathological or periprosthetic hip fracture
* Mechanism of injury for hip fracture was of high energy
* Patient is unable to comply with the study protocol or functional assessments
* Patients aged less than 60
* Patients who were wheelchair bound prior to injury
* Inability to understand the patient information for the study, provide written informed consent or answer study questionnaires for cognitive or language reasons
* Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
* Enrolment in existing research studies

Primary outcomes:
measure: Visual analogue scale score
timeFrame: On post operative day 1
measure: Ability to mobilise
timeFrame: On post operative day 1
Secondary outcomes:
measure: Visual analogue scale score
timeFrame: On post operative day 2
measure: Ability to mobilise
timeFrame: On post operative day 2
measure: EuroQol five dimension (EQ-5D) - 5L patient reported outcome measure
timeFrame: At post operative day (POD) 1, POD2, POD 7 and POD 30
measure: In hospital length of stay
timeFrame: From date of admission until the date of discharge from hospital or date of death, whichever came first (assessed up to 52 weeks)
measure: Total use of analgesia over post operative day 1 and post operative day 2
timeFrame: post operative day 1 and post operative day 2
measure: Complication rates and 30-day mortality
timeFrame: At post operative day (POD) 1, POD2, POD 7 and POD 30
measure: Discharge destination
timeFrame: Pre admission location will be assessed on the date of admission. Discharge destination will be sought, on the date of discharge from hospital (assessed up to 52 weeks)
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Lothian
Study officials:
affiliation: NHS Lothian
name: Nicholas Clement, MBBS, MD, PhD, FRCS (T&O)
role: PRINCIPAL_INVESTIGATOR
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