Study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK)

The clinical and cost effectiveness of peri-articular liposomal bupivacaine plus bupivacaine hydrochloride compared with bupivacaine hydrochloride alone for post-operative recovery after knee replacement surgery: A multi-centre, patient-blinded, randomised controlled trial.

Study Overview

• Status: Completed
• Conditions: Knee Osteoarthritis
• Intervention / Treatment: Drug: Liposomal bupivacaine; Drug: Bupivacaine hydrochloride

Detailed Description

The trial design is a patient-blinded multi-centre, active comparator, randomised controlled two-arm parallel group superiority trial of liposomal bupivacaine plus bupivacaine hydrochloride versus bupivacaine alone for post-operative pain in patients undergoing knee replacement surgery.

Patients will be randomised in a 1:1 ratio. The randomised controlled trial (RCT) design is robust and reduces any potential bias. Patients will be blinded as to which treatment they receive. Blinding of patients is possible as they will be under general anaesthetic for their knee replacement surgery at the time of the drug administration. Blinding of surgeons, who administer the medication and outcome assessors was not necessary as the primary outcome is a patient reported outcome measure.

• Study Type: Interventional
• Enrollment (Actual): 533
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom
    • The Royal Orthopaedic Hospital
  • Leeds, United Kingdom
    • Chapel Allerton Hospital
  • Lincoln, United Kingdom
    • Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust
  • London, United Kingdom
    • The Whittington Hospital
  • Oswestry, United Kingdom
    • Robert Jones and Agnes Hunt Orthopaedic Hospital
  • Rotherham, United Kingdom
    • Rotherham Hospital
  • Sutton In Ashfield, United Kingdom
    • King's Mill Hospital, Sherwood Forest Hospitals NHS Foundation Trust
  • Torquay, United Kingdom
    • Torbay Hospital
  • Wakefield, United Kingdom
    • Pinderfields Hospital - Mid Yorkshire
  • Yeovil, United Kingdom
    • Yeovil District Hospital
  • York, United Kingdom
    • York Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Unilateral primary knee replacement, including both total knee replacement (TKR) or unicompartmental knee replacement (UKR), for end stage osteoarthritis
• American Society of Anaesthesiologists (ASA) Grade I to III
• Participant is willing and able consent for themselves
• Male or Female, aged 18 years or above
• In the Investigator's opinion, is able and willing to comply with all trial requirements

Exclusion Criteria:

• Allergy or intolerance to amide type local anaesthetics
• Objective evidence of nerve damage in the affected lower limb.
• Rheumatoid arthritis
• 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.
• Participants who have participated in another research trial involving an investigational product in the past 6 months.
• Participants who have significant cognitive impairment or language issues
• Contra-lateral knee replacement within the trial or within 12 months prior to randomisation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Liposomal bupivacaine (EXPAREL); 266mg/20ml EXPAREL mixed with 80ml 0.9% normal saline and 100mg/20ml 0.5% plain bupivacaine hydrochloride. Administered as a single dose intra-operatively by periarticular infiltration.	Drug: Liposomal bupivacaine; 266mg/20ml vial of EXPAREL; Other Names: EXPAREL; Drug: Bupivacaine hydrochloride; 100mg/20ml 0.5% bupivacaine hydrochloride. Branded or generic, must be plain (cannot contain adrenaline/epinephrine); Other Names: Marcain
ACTIVE_COMPARATOR: Bupivacaine hydrochloride alone; 100ml 0.9% normal saline mixed with 100mg/20ml 0.5% plain bupivacaine hydrochloride. Administered as a single dose intra-operatively by periarticular infiltration.	Drug: Bupivacaine hydrochloride; 100mg/20ml 0.5% bupivacaine hydrochloride. Branded or generic, must be plain (cannot contain adrenaline/epinephrine); Other Names: Marcain

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Recovery 40 (QoR-40)	A 40-item instrument which encompass most aspects of a good quality of recovery after surgery. Consists of five clinically relevant dimensions: Physical comfort (12 items); Emotional state (9 items); Physical independence (5 items); Psychological support (7 items); Pain (7 items). The QoR-40 has a possible score of 40 (extremely poor quality of recovery) to 200 (excellent quality of recovery).	Change in score between 0, 24, 48 and 72 hours post-operatively
Cumulative 0-10 pain Visual Analogue Score (VAS)	Cumulative daily pain score at rest. A 10 point scale where 0 = no pain, 5 = moderate pain and 10 = worst possible pain.	Cumulative score at 0, 24, 48 and 72 hours post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean 0-10 pain Visual Analogue Score (VAS)	Mean daily pain score at rest. A 10 point scale where 0 = no pain, 5 = moderate pain and 10 = worst possible pain.	0, 24, 48 and 72 hours post-operatively
Opioid consumption	Cumulative consumption	Change in consumption between 0, 24, 48 and 72 hours post-operatively
Fitness for discharge (as per routine clinical care)	Against pre-defined criteria. Patients would be considered fit for discharge when they meet the following criteria: Ability to mobilize independently; pain score less than or equal to 3mm on a 10 VAS; ability to straight leg raise and ability to bend knee to 90 degrees	Assessed at 0, 24, 48 and 72 hours post-operatively
Oxford Knee Score (OKS)	Functional outcome using validated, patient reported questionnaire	Change in score between baseline, 72 hours, 6 weeks, 6 months, 1 year post-operatively
American Knee Society Score (AKSS)	Functional outcome using validated, patient reported questionnaire	Change in score between baseline, 72 hours, 6 weeks, 6 months, 1 year post-operatively
EuroQol 5 Dimension scale	Validated patient reported quality of life questionnaire	Change in score between baseline, 72 hours, 6 weeks, 6 months, 1 year post-operatively
Health economics	Cost utility analysis	Change in cost utility between baseline, 6 weeks, 6 months, 1 year post-operatively
Serious Adverse Events (SAE)	Specifically cardiovascular or wound complications	Within 30 days of surgery

Collaborators and Investigators

• Sponsor: University of Leeds
• Collaborators: University of Oxford
• Investigators: Principal Investigator: Hemant Pandit, University of Leeds

Publications and helpful links

Helpful Links

• SPAARK website

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 29, 2018
• Primary Completion (ACTUAL): February 28, 2021
• Study Completion (ACTUAL): April 21, 2021

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 25, 2017
• First Posted (ACTUAL): October 31, 2017

Study Record Updates

• Last Update Posted (ACTUAL): November 4, 2022
• Last Update Submitted That Met QC Criteria: November 3, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: OR16/88494; 2016-003154-32 (EUDRACT_NUMBER); 197936 (OTHER: Integrated Research Application System (IRAS))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes