Trial Background & Design | SPAARK: Study of Peri-Articular Anaesthetic for Replacement of the Knee

SPAARK: Study of Peri-Articular Anaesthetic for Replacement of the Knee

A phase III, multi-centre, patient blinded, randomised controlled trial (RCT).

Background: Around 100,000 primary knee replacement surgeries were performed in the UK last year. Knee replacement is highly successful for treating moderate to severe arthritis however, the surgery is painful and nearly half of patients report severe pain post-operatively. If pain is not controlled, it slows recovery and can lead to complications. In addition, experiencing prolonged pain after surgery leads to longer hospital stays and patient dissatisfaction.

Following knee replacement, the pain is worst over the first 72 hours with pain control provided by a combination of tablets and local anaesthetic (LA) injected around the knee. The duration of current LAs is limited to around 12 to 24 hours with patients often getting significant breakthrough pain the morning following surgery when the LA has worn off and they are encouraged to start physiotherapy.

A new formulation of LA, liposomal bupivacaine, has been widely used in the USA since 2011 but is not yet licensed in the UK. It is reported to give pain relief over 72 hours and across a range of surgeries has been reported to improve pain control, reduce the need for additional pain killers and result in a shorter hospital stays compared to current LAs.

Primary Endpoint: Evaluate the effectiveness of liposomal bupivacaine with bupivacaine hydrochloride compared to bupivacaine hydrochloride alone on post-operative recovery. Assessed both in terms of systemic recovery as well as local recovery of the operated joint.

Secondary Endpoints:

To assess other markers of recovery both in the short term and long term.
To evaluate the cost effectiveness of the intervention compared with the current standard of care.
Safety - Serious Adverse Events (SAEs), specifically cardiovascular or wound complications within 30 days of surgery.

1 - RECRUITMENT

Looking to recruit up to 500 patients from up to 10 NHS sites over a period of 18 months.

INCLUSION CRITERIA

Unilateral primary knee replacement, including both total knee replacement (TKR) or unicompartmental knee replacement (UKR) for end stage osteoarthritis of the knee

American Society of Anaesthesiologists (ASA) Grade I to III

Willing and able to consent for themselves

Male or Female, aged 18 or above

Able and willing to comply with all trial requirements

EXCLUSION CRITERIA

Allergy or intolerance to amide-type local anesthetics

Nerve damage in affected limb

Rheumatoid arthritis

Any significant disease, disorder or condition which may put the participant at risk

Involvement in other research

Significant cognitive impairment or language issues

Contra-lateral knee replacement within the trial or within 12 months prior to randomisation

2 - TREATMENT ALLOCATION (RANDOMISATION)

Patients entered into the trial will be randomised to either receive the interventional, or control (standard of care):

Intervention arm: Liposomal bupivacaine plus bupivacaine hydrochloride (250 patients)

Control arm: Bupivacaine hydrochloride only (250 patients)

3 - KNEE REPLACEMENT SURGERY

Drug administered as single intra-operative peri-articular injection as part of multimodal analgesia

4 - IN-PATIENT (0 - 72 HOURS POST-SURGERY)

Data collected: QoR-40, pain VAS at rest; cumulative opiate use; EQ-5D-5L

5 - SIX WEEK FOLLOW UP

Postal questionnaire

Data collected: Summary medication history; summary healthcare & social services use; QoR-40; summary employement history; pain VAS at rest; EQ-5D-5L; Oxford Knee Score; American Knee Society Score

6 - SIX MONTH FOLLOW UP

Postal questionnaire

7 - ONE YEAR FOLLOW UP

Postal questionnaire

Data collected: Summary medication history; summary healthcare & social services use; summary employement history; pain VAS at rest; EQ-5D-5L; Oxford Knee Score; American Knee Society Score (function only)