Perineural local anaesthetic catheter after major lower limb amputation trial (PLACEMENT)
| ISRCTN | ISRCTN72547749 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN72547749 |
| IRAS number | 1006695 |
| Secondary identifying numbers | 1854-21, IRAS 1006695, CPMS 55264 |
- Submission date
- 23/12/2022
- Registration date
- 12/09/2023
- Last edited
- 02/07/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English Summary
Background and study aims
Leg amputations are painful and life-changing events. About 10000 people have a leg amputation in the UK every year. Pain may be felt in the stump straight after surgery and in the longer term. Pain may also be felt in the foot which is no longer there. This is called ‘phantom pain’ and may interfere with fitting and using an artificial leg. Long term pain may also delay recovery and limit what people can do for the rest of their lives. Morphine is often used to help with pain. However, morphine has major side effects, including sickness, confusion, and breathing problems. Reducing pain after amputation is an important topic. A 2014 review showed that only 1 out of every 3 patients in the UK had the ‘best’ pain relief after amputation.
Who can participate?
This research will take place in 20 NHS hospitals. 650 patients having an amputation because of blocked arteries and/or diabetes will take part.
What does the study involve?
This research will test a method for managing pain after leg amputation. It involves the surgeon placing a tiny tube, called a ‘perineural catheter,’ next to the main nerve which is cut during surgery. Local anaesthetic is slowly pumped into the tube for up to the first 5 days after surgery. Putting the tube in and taking it out is simple and problems are rare. The tube can replace some (or all) of the morphine often needed. The tube may also reduce phantom pain.
The research will be a ‘randomised’ trial. This means patients having amputation surgery will be randomly chosen by a computer to either have the tube or not. Everything else will be the same. All patients will have the best anaesthetic and pain control medication. The amount of pain will then be compared between those who did and those who did not have the tube. The amount of pain, morphine used, painkiller side effects, and surgery complications will be recorded for up to 5 days after the amputation surgery. We will ask patients about their pain and if they are walking on an artificial leg 3 and 6 months after their amputation.
What are the possible benefits and risks of participating?
Benefits:
This research is aiming to find out if the placement of a tiny tube (catheter) during amputation surgery, and delivery of a local anaesthetic through the tube for five days after surgery, will affect the amount of short- and long-term pain experienced by participants, compared with those who do not receive the tube and local anaesthetic. If pain is reduced, this may lead to lower morphine use and fewer side effects, which could help to improve recovery after amputation surgery. Participants will be helping to answer questions about the treatment of lower limb amputation that may result in improved pain management for patients undergoing lower limb amputation in the future.
Risks:
The major burden on participants is the time taken to complete pain and quality of life questionnaires for the first 5 days following their amputation surgery, and 3 and 6 months after their operation. While there are also theoretical risks associated with placement of a perineural nerve catheter (PNC), this procedure is performed routinely and does not seem to be associated with more than very rare complications. This has not been formally studied previously, however, so it is possible that complications simply have not been previously noticed. We will minimise the risks associated with this by routine review by a trial steering committee, which will look at complication rates while the study is running and can call a halt to the study if unexpected complications arise.
Where is the study run from?
Cardiff University (UK)
When is the study starting and how long is it expected to run for?
September 2022 to March 2026
Who is funding the study?
NIHR Health Technology Assessment (HTA) (UK)
Who is the main contact?
placement-trial@cardiff.ac.uk
Contact information
Scientific
Centre for Trials Research
7th Floor
Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
United Kingdom
| Phone | +44 29 20687418 |
|---|---|
| placement-trial@cardiff.ac.uk |
Principal Investigator
University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom
| Phone | +44 29 2074 2316 |
|---|---|
| david.bosanquet@wales.nhs.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | Perineural Local Anaesthetic Catheter aftEr Major lowEr limb amputatioN Trial (PLACEMENT) |
| Study acronym | PLACEMENT |
| Study hypothesis | Primary objective: To compare 'freedom from pain' in participants following major lower limb amputation (MLLA) randomised to receive perineural catheter (PNC) placement with participants following MLLA randomised not to receive PNC placement. Freedom from pain is defined as the proportion of pain scores with self-reported pain ≤3 on a 0 to 10 Numeric Rating Scale (NRS). Pain scores will be assessed twice daily for the first five days following amputation surgery. Secondary objectives include assessing the effect of PNC placement on: 1. Participant satisfaction of pain management, total opioid use and opioid side effects for the first five days after surgery 2. The rate and severity of postoperative complications rate at discharge 3. Surgical site infection at 30 days 4. Hospital stays, including re-admissions after discharge at 90 days 5. Phantom limb pain, chronic stump pain, residual limb surgery, delayed wound healing, health-related quality of life, depression, time to achieve prosthesis fitting (if applicable), level of independence, MLLA of contralateral limb (for unilateral amputees), healthcare resource use, cost-effectiveness, and mortality at 3 and 6 months. |
| Ethics approval(s) |
Approved 31/07/2023, East Midlands - Leicester Central Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8284; leicestercentral.rec@hra.nhs.uk), ref: 23/EM/0020 |
| Condition | Major lower limb amputation, including above- below- and through knee amputation, for complications of chronic diseases, including peripheral arterial disease and diabetes. |
| Intervention | All participants recruited into the trial are scheduled to undergo either an above knee, below knee, or through knee amputation for complications of peripheral vascular disease or diabetes. The intervention arm will receive a perineural catheter (PNC), placed adjacent to the sciatic nerve for above knee amputations or adjacent to the tibial nerve for below knee amputations. Local anaesthetic (Levobupivacaine hydrochloride 0.125 to 0.25%, 1 to 15mg/hr, maximum 400mg per 24 hours OR Ropivacaine hydrochloride 0.2%, 10 to 20mg/hr, maximum 800mg per 24 hours OR Bupivacaine hydrochloride 0.1 to 0.25%, maximum 400mg per 24 hours) will be infused via the PNC for the first five postoperative days. Additional postoperative pain will be managed with standard analgesics, including morphine, as required. The control arm will not receive a PNC during amputation. Postoperative pain will be managed with standard analgesics, including morphine, as required. Follow-up activity for both trial arms: Participants’ pain scores will be assessed twice daily for the first five postoperative days. Participants will be followed up for additional short and long-term pain and health-related quality of life outcomes at three and six months postoperatively. Randomisation process will primarily use an online tool with a telephone backup. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | Levobupivacaine hydrochloride, ropivacaine hydrochloride monohydrate, bupivacaine hydrochloride anhydrous |
| Primary outcome measure | Freedom from pain, defined as the proportion of time points with self-reported pain ≤3 using an 11-point Numeric Rating Scale (NRS, range 0 to 10) assessed twice daily for the first five postoperative days. |
| Secondary outcome measures | (Up to 5 days) 1. Participant satisfaction related to pain management during the preceding 24 h, assessed pre-operatively and once daily postoperatively for up to five days using a 4-point Likert scale 2. Opioid use assessed once daily postoperatively for five days, converted to morphine equivalents using the University of Alberta Multidisciplinary Pain Centre Opioid Conversion Guide 3. Opioid side effects (frequency and severity of symptoms) assessed once daily postoperatively for five days (At discharge) 4. Morbidity, assessed using Clavien-Dindo grading at discharge 5. Length of hospital stay (At 30 days) 6. Surgical site infection rates classified as per the 2008 CDC/NHSN document assessed at 30 days (At 90 days) 7. Days alive and out of hospital assessed at 90 days (DAOH-90) (At 3 to 6 months) 8. Chronic residual limb pain assessed at 3 and 6 months 9. Phantom limb pain assessed at 3 and 6 months 10. Length of hospital stay assessed at 3 and 6 months 11. Residual limb surgery assessed at 30 days, 3 months, and 6 months 12. Health-related QoL assessed using EQ-5D-5L at 3 months and 6 months 13. Participant reported anxiety and depression assessed using HADS at 3 months and 6 months 14. Prosthesis fitting assessed as rate and time to fitting using SIGAM at 3 and 6 months 15. Assessment of health care resource usage during the first 6 months postoperatively 16. Mortality assessed at 6 months. |
| Overall study start date | 01/09/2022 |
| Overall study end date | 31/03/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 650 |
| Participant inclusion criteria | Current participant inclusion criteria as of 02/07/2024: 1. Aged 18 years or older 2. Undergoing elective or emergency MLLA (BKA, TKA, or AKA) for complications of PAD, diabetes, or acute or chronic infection 3. Able to assess pain using NRS 4. Life expectancy of greater than two weeks 5. (For people of childbearing potential) Willing to undergo a preoperative pregnancy test and agree to either use a highly effective method of contraception or abstain from sexual intercourse for 7 days after MLLA. 6. (For male participants with female sexual partners who are considered to be of childbearing potential)* Willing to agree to use a condom or abstain from sexual intercourse for seven days after MLLA Previous participant inclusion criteria: 1. Aged 18 years or older 2. Undergoing elective or emergency MLLA (BKA, TKA, or AKA) for complications of PAD and/or diabetes 3. Able to assess pain using NRS 4. Life expectancy of greater than two weeks 5. (For people of childbearing potential) Willing to undergo a preoperative pregnancy test and agree to either use a highly effective method of contraception or abstain from sexual intercourse for 7 days after MLLA. 6. (For male participants with female sexual partners who are considered to be of childbearing potential)* Willing to agree to use a condom or abstain from sexual intercourse for seven days after MLLA |
| Participant exclusion criteria | Current participant exclusion criteria as of 02/07/2024: 1. Undergoing MLLA for trauma or cancer 2. Undergoing digital, metatarsal, tarsal amputation, disarticulation of the hip or hindquarter amputation 3. Undergoing simultaneous bilateral amputations 4. Undergoing MLLA revision (excluding previous guillotine amputation) 5. Allergy or intolerance to the PNC or local anaesthetic agents, or chronically taking class 1B anti-arrhythmic agents or local anaesthetic agents, for example in the form of transdermal patches. 6. Expected to be sedated for more than 24 hours postoperatively 7. Unable to provide consent due to incapacity (as defined by the Mental Capacity Act 2005) 8. Vulnerable or protected adults. 9. People who are currently pregnant or breastfeeding 10. Previously enrolled in PLACEMENT (excluding PLACEMENT feasibility trial) for a prior MLLA Previous participant exclusion criteria: 1. Undergoing MLLA for trauma or cancer 2. Undergoing digital, metatarsal, tarsal amputation, disarticulation of the hip or hindquarter amputation 3. Undergoing simultaneous bilateral amputations 4. Undergoing MLLA revision 5. Allergy or intolerance to the PNC or local anaesthetic agents, or chronically taking class 1B anti-arrhythmic agents or local anaesthetic agents, for example in the form of transdermal patches. 6. Expected to be sedated for more than 24 hours postoperatively 7. Unable to provide consent due to incapacity (as defined by the Mental Capacity Act 2005) 8. Vulnerable or protected adults. 9. People who are currently pregnant or breastfeeding 10. Previously enrolled in PLACEMENT (excluding PLACEMENT feasibility trial) for a prior MLLA |
| Recruitment start date | 01/09/2023 |
| Recruitment end date | 01/09/2025 |
Locations
Countries of recruitment
- United Kingdom
- Wales
Study participating centres
Cardiff
CF14 4XW
United Kingdom
Westbury-on-trym
Bristol
BS10 5NB
United Kingdom
Cwmrhydyceirw
Swansea
SA6 6NL
United Kingdom
London
W2 1BL
United Kingdom
Leicester
LE3 9QP
United Kingdom
Hull
HU3 2JZ
United Kingdom
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Liverpool
L7 8XP
United Kingdom
Westcliff-on-sea
SS0 0RY
United Kingdom
Sponsor information
University/education
Centre for Trials Research
Neuadd Meirionnydd
Heath Park
Cardiff
CF14 4YS
Wales
United Kingdom
| Phone | +44 (0)29 20687418 |
|---|---|
| placement-trial@cardiff.ac.uk | |
| Website | http://www.cardiff.ac.uk/ |
"ROR" |
https://ror.org/03kk7td41 |
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- NIHR Health Technology Assessment Programme, HTA
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/03/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Peer reviewed scientific journals Internal report Conference presentation Publication on website Other publication Other The findings will be presented at medical conferences, published in free to access medical journals, and shared with people who write amputation surgery guidelines and policies. We will share results via the national press, amputation charities and social media. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 1.1 | 14/07/2023 | 26/09/2023 | No | No |
Additional files
Editorial Notes
02/07/2024: The following changes were made:
1. The participant inclusion and exclusion criteria were changed.
2. The following study participating centres were added: Southmead Hospital, Morriston Hospital, St Marys Hospital, Glenfield Hospital, Hull Royal Infirmary, Freeman Hospital, Cambridge University Hospitals NHS Foundation Trust, Royal Liverpool University Hospital, and Mid and South Essex NHS Foundation Trust.
04/10/2023: Internal review.
26/09/2023: Protocol file uploaded.
02/08/2023: ISRCTN received notification of combined HRA/MHRA approval for this trial on 02/08/2023
23/12/2022: Trial's existence confirmed by NHS HRA.
