LOLIPOP: Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain

BACKGROUND: Moderate or severe Chronic Post-Surgical Pain (CPSP) affects up to 27% of patients undergoing breast cancer surgery in the UK. Perioperative systemic lidocaine infusion is consistently identified as the most promising preventative agent. The LOLIPOP RCT has started recruitment in Australasia to test this intervention in breast cancer surgery. International differences in care pathways - particularly day case breast surgery in the UK, with less opportunity for prolonged postoperative lidocaine infusion - mean that substantial UK recruitment is needed to generalise the trial findings to the NHS.

AIM 1: Test the primary hypothesis that lidocaine infusion intraoperatively and up to 24h postoperatively will decrease the incidence of moderate or severe CPSP 1 year after primary breast cancer surgery.
AIM 2: To provide UK-specific efficacy, safety and cost-effectiveness data

METHODS: UK arm of an established, pragmatic, international, multi-centre, randomised, placebo-controlled, safety and superiority trial with quadruple blinding, internal pilot and patient follow-up for 1 year. Adult females undergoing mastectomy or breast conserving surgery for the primary excision of cancer in NHS hospitals will be enrolled; n≥1,000, representing ≥20% of the international sample size of 4,300. Participants will be randomised (1:1) to lidocaine or matched placebo (0.9% saline) infusion dosed on lean body weight and starting intravenously (2.5mg/kg bolus then 3.33 mg/kg/h) before surgical incision and continuing subcutaneously (2.22 mg/kg/h) for up to 24h postoperatively (less if discharged; day case patients will have the iv lidocaine stopped in the recovery room). Single shot LA blocks (e.g. PECS) up to a recommended dose limit are permitted within the trial.

We will use trial processes that exhibited excellent safety, effectiveness and feasibility in our external multi-centre pilot (n=150). The primary outcome is the patient reported incidence of moderate or severe CPSP 1 year after surgery using a numerical rating scale (NRS 0-10) ≥4/10 for worst pain in the last 7 days. Secondary outcomes include: pain character/severity; opioid consumption; physical functioning; quality of life; psychological wellbeing; and safety endpoints. A UK economic evaluation will be conducted from an NHS perspective at 1 year.

TIMELINES: International study ends in January 2029. Study duration in UK is 60 months from January 2024 to January 2029: 4 months set-up; 38 months recruitment (12-month internal pilot); 12 months follow-up; 6 months analysis/report. Target randomisation 2.6 patients/centre/month across 10 centres.

TRIAL MANAGEMENT: Bristol Trials Centre working with UK lead Dr Mark Edwards. LOLIPOP will be a Clinical Trial of an Investigational Medicinal Product (CTIMP). Sites will be provided with ready packaged IMP/placebo and pre-programmed infusion pumps. Site payment of ~£6000 to cover setup and IMP management, per-participant payment ~£200per participant (plus support and treatment costs) to cover recruitment, intervention delivery and data collection. Joint anaesthesia/breast surgery leadership suggested at a local level.