Liposomal bupivacaine in knee replacement surgery
| ISRCTN | ISRCTN54191675 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN54191675 |
| EudraCT/CTIS number | 2016-003154-32 |
| Secondary identifying numbers | 32227 |
- Submission date
- 13/11/2017
- Registration date
- 14/11/2017
- Last edited
- 28/11/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English Summary
Background and study aims
At the moment, in the UK, a local anaesthetic (a medication that numbs an area of the body) called bupivacaine hydrochloride is routinely used during knee replacement surgery. This drug is injected around the knee at the time of surgery to help reduce the levels of pain experienced afterwards. There is a new local anaesthetic called liposomal bupivacaine (also known as Exparel) that has been used routinely in the USA since 2011. Using Exparel will help to reduce the level of pain experienced after surgery, but it is thought that the pain relief may be felt for longer. The aim of this study is to compare these two local anaesthetic injections against each other, and show whether or not there is an extended period of pain relief when Exparel is used as well as to see if using Exparel reduces the need for other types of pain relief post-operation. This study will also look at the cost of using Exparel, and whether it would be a cost-effective alternative to the current treatment.
Who can participate?
Adults aged 18 and older who have end stage osteoarthritis of the knee.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive the liposomal bupivacaine. Those in the second group receive the bupivacaine. The surgical team performing the operation administers the drug via wound infiltration during surgery. After the operation, the patient will be cared for as per routine care at the hospital. For 3 days (72 hours) after the surgery, the patient will be asked to complete a daily questionnaire so that the study team can find out how they are feeling after the surgery. Participants are asked about their recovery throughout hospitalisation and at six weeks, six months and one year postoperatively.
What are the possible benefits and risks of participating?
Whilst Exparel is not currently used routinely in the United Kingdom, it has been used in the United States since 2011 and the safety profile has been reviewed both independently and with the UK regulators (Medicines and Healthcare products Regulatory Agency) prior to this trial.
The main benefit of taking part will be the information the researchers get from this study which will help them assess how patients do after receiving this anaesthetic. This will improve treatment of future patients with knee osteoarthritis. There are no anticipated risks or disadvantages to participating in SPAARK. The operation will be performed by an experienced and trained Consultant Surgeon. There are risks associated with all surgery and anaesthetics. Steps are always taken to ensure that these risks are minimised. As part of routine care, the patient will be well informed of potential risks. Participating in this study will not affect the standard of care received. The most common side effects of Exparel administration are nausea, constipation and vomiting. These are also side effects associated with having a general anaesthetic for an operation. Most patients (9 out of 10) do not experience these side effects.
Where is the study run from?
This study is being run by the Surgical Intervention Trials Unit (SITU) at the University of Oxford (UK).
When is the study starting and how long is it expected to run for?
November 2017 to February 2021
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
SITU-NDORMS, situ@ndorms.ox.ac.uk
Contact information
Public
Surgical Intervention Trials Unit (SITU)
Nuffield Department. of Orthopaedics, Rheumatology & Musculoskeletal Sciences (NDORMS)
The Botnar Research Centre
University of Oxford
Windmill Road
Oxford
OX3 7HE
United Kingdom
| Phone | +44 1865 223665 |
|---|---|
| situ@ndorms.ox.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug, Surgery |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Study of Peri-Articular Anaesthetic for Replacement of the Knee. The clinical and cost effectiveness of peri-articular liposomal bupivacaine compared with bupivacaine hydrochloride for post-operative recovery after knee replacement surgery: A multi-centre, blinded, randomised controlled trial |
| Study acronym | SPAARK |
| Study hypothesis | This study aims to evaluate the effectiveness of liposomal bupivacaine versus standard bupivacaine on post-operative recovery for total knee replacement patients. |
| Ethics approval(s) | South Central - Oxford C Research Ethics Committee, 19/07/2017, ref: 17/SC/0139 |
| Condition | Elective orthopaedic surgery |
| Intervention | Patients with osteoarthritis of the knee that require a knee replacement operation are asked to take part in the study. During the clinic appointment, the surgeon tells the patient a little bit about the study and the local research nurses discuss the study and what it involves. This should take about 10 minutes. If the patient is interested in participating, they are assessed by one of the research team to answer some questions about their knee function and are asked to complete a questionnaire. The researcher also examines the knee. During the knee operation, as part of the routine operation, the surgeon injects local anaesthetic around the knee. If a patient consents to participate they are randomly assigned to receive either the current local anaesthetic injection (bupivacaine hydrochloride) or the new trial local anaesthetic injection (liposomal bupivacaine). Both injections are given using the same technique before the surgeon finishes the operation. After the operation, the patient will be cared for as per routine care at the hospital. For 3 days (72 hours) after the surgery, the participant are asked to complete a daily questionnaire so that the study team can find out how they are feeling after the surgery. Routine hospital follow-up for this operation is at approximately six weeks and six months post-surgery. The SPAARK assessments are scheduled at the same time so that the participants do not have to make an extra ‘research only’ visit to the hospital. Ahead of these appointments, the participants are sent a questionnaire to complete and return (either by post or email). A questionnaire is also sent one year after the operation. This should take about half an hour to complete. Allocation to either local anaesthetic is done randomly as this is the best way to allow a fair comparison to be made between the two treatments. This is the standard and only reliable way to see how good a treatment is. Whichever local anaesthetic is allocated, the patient will still be under the care of their surgeon and their professional clinical team. The patient does not know which local anaesthetic they receive as SPAARK is a “blinded” trial. The surgeon knows which medication the patient is allocated to, but for the purposes of the study, the patient is not be told. The reason for this is to stop the patient’s questionnaire answers from being influenced by which medication they were allocated. This information is kept confidential unless there is a problem. |
| Intervention type | Other |
| Primary outcome measure | The effectiveness of liposomal bupivacaine with bupivacaine hydrochloride compared to bupivacaine hydrochloride alone on post-operative recovery is assessed both in terms of systemic recovery as well as local recovery of the operated joint. This will be measured using the quality of recovery 40 Score at 72 hours and the cumulative daily pain score at rest using VAS 0 to 72 hours. |
| Secondary outcome measures | 1. Other markers of recovery both in the short term and long term are measured using: 1.1. Mean pain score measured using a 0-10 VAS at: baseline and evening of surgery day 0, 1, 2 and 3 following surgery 1.2. Quality of Recovery 40 Score at baseline and evening of surgery day 0, 1, 2 and 3 following surgery 1.3. Cumulative opioid consumption over 72 hours. 1.4. Fitness for discharge against pre-defined criteria at evening of surgery day 0, 1, 2 and 3 following surgery 1.5. Functional outcome at baseline, 6 weeks, 6 months and 1 year (Oxford Knee Score, American Knee Society Score) 2. Cost effectiveness of the intervention compared with the current standard of care is measured using cost utility analysis using patient-reported quality of life as the main outcome, obtained using the EuroQol EQ-5D-5L questionnaire at baseline, 72 hours, 6 weeks, 6 months and 1 year 3. Safety is measured using serious adverse events, specifically cardiovascular or wound complications within 30 days of surgery |
| Overall study start date | 01/04/2017 |
| Overall study end date | 28/02/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 500; UK Sample Size: 500 |
| Total final enrolment | 533 |
| Participant inclusion criteria | Current participant inclusion criteria as of 11/01/2019: 1. Unilateral primary knee replacement, including both total knee replacement (TKR) and unicompartmental knee replacement (UKR), for end-stage osteoarthritis 2. American Society of Anaesthesiologists (ASA) Grade I to III 3. Participant is willing and able to consent for themselves 4. Male or female, aged 18 years or above 5. In the Investigator’s opinion, is able and willing to comply with all trial requirements Previous participant inclusion criteria as of 26/10/2018: 1. Unilateral primary knee replacement, including both total knee replacement (TKR) or unicompartmental knee replacement (UKR), for end stage osteoarthritis 2. Willing and able consent for themselves 3. Male or female, aged 18 years or above 4. In the Investigator’s opinion, is able and willing to comply with all trial requirements. Previous participant inclusion criteria: 1. Participant is willing and able consent for themselves 2. Male or Female, aged 18 years or above 3. End stage osteoarthritis of the knee 4. In the Investigator’s opinion, is able and willing to comply with all trial requirements |
| Participant exclusion criteria | Current participant exclusion criteria as of 11/01/2019: 1. Allergy or intolerance to amide-type local anaesthetics 2. Objective evidence of nerve damage in the affected lower limb 3. Rheumatoid arthritis 4. Any other significant disease, disorder or condition which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the results of the trial, or the participant’s ability to participate in the trial 5. Participants who have participated in another research trial involving an investigational product in the past 6 months 6. Participants who have significant cognitive impairment or language issues 7. Contra-lateral knee replacement within the trial or within 12 months prior to randomization Previous participant exclusion criteria as of 26/10/2018: 1. American Society of Anaesthesiologists (ASA) Grade III or above 2. Allergy or intolerance to amide type local anaesthetics 3. Objective evidence of nerve damage in the affected lower limb 4. Rheumatoid arthritis 5. Any other significant disease, disorder or condition which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the results of the trial, or the participant’s ability to participate in the trial 6. Participants who have participated in another research trial involving an investigational product in the past 6 months 7. Participants who have significant cognitive impairment or language issues 8. Contra-lateral knee replacement within the trial or within 12 months prior to randomisation Previous participant exclusion criteria: 1. American Society of Anaesthesiologists (ASA) Grade III or above 2. Allergy or intolerance to amide type local anaesthetics 3. Objective evidence of nerve damage in the affected lower limb 4. Rheumatoid arthritis 5. Any other significant disease, disorder or condition which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial. 6. Participants who have participated in another research trial involving an investigational product in the past 6 months 7. Participants who have significant cognitive impairment or language issues 8. Contra-lateral knee replacement (If the patient is receiving staged bilateral knees, they may still participate in the trial but data will only be included from the first knee) |
| Recruitment start date | 27/11/2017 |
| Recruitment end date | 29/02/2020 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
Leeds
LS7 4SA
United Kingdom
Wakefield
WF1 4DG
United Kingdom
Rotherham
S60 2UD
United Kingdom
Oswestry
SY10 7AG
United Kingdom
Torquay
TQ2 7AA
United Kingdom
London
N19 5NF
United Kingdom
Boston
PE21 9QS
United Kingdom
Yeovil
BA21 4AT
United Kingdom
Sutton-in-Ashfield
NG17 4JL
United Kingdom
Sponsor information
Hospital/treatment centre
Joint Leeds Sponsor Office
Research & Innovation
34 Hyde Terrace
Leeds
LS2 9LN
England
United Kingdom
"ROR" |
https://ror.org/024mrxd33 |
|---|
Funders
Funder type
Government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/08/2021 |
|---|---|
| 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 | Results of this trial will be submitted for publication in a peer‐reviewed journal. All presentations and publications will be pre‐agreed by the Trial Steering Committee (TSC). |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 16/12/2019 | 18/12/2019 | Yes | No |
| Statistical Analysis Plan | statistical analysis plan | 17/05/2021 | 19/05/2021 | No | No |
| Results article | 06/04/2022 | 07/04/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
28/11/2024: The contact details were changed.
07/04/2022: Publication reference added.
19/05/2021: Publication reference added.
06/03/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/02/2020 to 29/02/2020.
2. The overall trial end date was changed from 01/04/2020 to 28/02/2021.
3. The intention to publish date was changed from 01/04/2020 to 31/08/2021.
4. The total final enrolment number was added.
18/12/2019: Publication reference added.
11/06/2019: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/04/2019 to 01/02/2020.
2. The plain English summary was updated to reflect this change.
29/03/2019: The condition has been changed from "Specialty: Musculoskeletal disorders, Primary sub-specialty: Elective Orthopaedic Surgery; UKCRC code/ Disease: Musculoskeletal/ Other joint disorders" to "Elective orthopaedic surgery" following a request from the NIHR.
11/01/2019: The following changes have been made:
1. The participant inclusion criteria have been changed.
2. The participant exclusion criteria have been changed.
26/10/2018: The following changes have been made to the trial record:
1. The participant inclusion criteria have been updated
2. The participant exclusion criteria have been updated
3. University of Oxford Surgical Intervention Trials Unit (SITU) was removed as a trial participating centre
4. Chapel Allerton Hospital, Pinderfields Hospital, Rotherham General Hospital, The Robert Jones and Agnes Hunt Orthopaedic Hospital, Torbay Hospital, The Whittington Hospital, Pilgrim Hospital, Yeovil District Hospital and King's Mill Hospital were added as trial participating centres
