Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial (LOLIPOP)

The LOLIPOP Trial is a large (n=4,300 patients) pragmatic, international, multicentre, prospective, randomised, double blind, placebo-controlled, parallel assessment, safety and effectiveness superiority study.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Mastectomy; Breast Cancer Female; Breast Conserving Surgery
• Intervention / Treatment: Drug: lidocaine 2% and 10%; Drug: Placebo

Detailed Description

The Trial's purpose is to evaluate the effectiveness of lidocaine infusions commenced during surgery and extending up to 24 hours postoperatively, on the incidence of moderate or severe chronic post-surgical pain (CPSP) detected one year following surgery in female patients undergoing elective breast cancer surgery. The trial has 90% power to detect a clinically meaningful (25%) reduction in the incidence of the primary outcome. Secondary outcomes include safety events, analgesic efficacy (pain scores and opioid consumption), neuropathic characteristics of CPSP, and psychological and quality of life outcomes.

• Study Type: Interventional
• Enrollment (Estimated): 4300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Gillian Ormond; Phone Number: +610399030387; Email: gillian.ormond@monash.edu
• Study Contact Backup: Name: Natalie Hird; Phone Number: +61 (0) 459 407 231; Email: natalie.hird@health.wa.gov.au

Study Locations

• Australia
  • New South Wales
    • Kingswood, New South Wales, Australia, 2747
      • Recruiting
      • Nepean Hospital
    • Mount Druitt, New South Wales, Australia, 2770
      • Recruiting
      • Blacktown Mount Druitt Hospital
    • Sydney, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
    • Sydney, New South Wales, Australia, 2217
      • Recruiting
      • St George Hospital
    • Sydney, New South Wales, Australia, 2035
      • Recruiting
      • Royal North Shore Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Recruiting
      • Royal Brisbane and Women's Hospital
    • Coopers Plains, Queensland, Australia, 4108
      • Recruiting
      • Queen Elizabeth II Jubilee Hospital
    • Mackay, Queensland, Australia, 4740
      • Recruiting
      • Mackay Base Hospital
    • Rockhampton, Queensland, Australia, 4700
      • Terminated
      • Rockhampton Hospital
    • Southport, Queensland, Australia, 4215
      • Terminated
      • Gold Coast Hospital and Health Service- Gold Coast University Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Recruiting
      • Flinders Medical Centre
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Recruiting
      • Royal Hobart Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Recruiting
      • Ballarat Health Services (Grampians Health)
    • Ballarat, Victoria, Australia, 3350
      • Terminated
      • Anaesthetic Group Ballarat
    • Geelong, Victoria, Australia, 3220
      • Recruiting
      • Barwon Health - University Hospital Geelong
    • Melbourne, Victoria, Australia, 3050
      • Recruiting
      • Royal Melbourne Hospital
    • Melbourne, Victoria, Australia, 3065
      • Recruiting
      • St Vincent's Hospital Melbourne
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • The Alfred
    • Melbourne, Victoria, Australia, 3165
      • Completed
      • Monash Health - Moorabbin Hospital
    • Melbourne, Victoria, Australia, 3076
      • Withdrawn
      • Northern Hospital
    • Ringwood East, Victoria, Australia, 3135
      • Recruiting
      • Maroondah Hospital - Eastern Health
    • Shepparton, Victoria, Australia, 3630
      • Terminated
      • Goulburn Valley Health
    • Traralgon, Victoria, Australia, 3844
      • Withdrawn
      • Latrobe Regional Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Recruiting
      • Royal Perth Hospital
    • Perth, Western Australia, Australia, 6008
      • Recruiting
      • St John of God Subiaco
      • Contact: Natalie Hird; Phone Number: +61 459 407 231; Email: Natalie.Hird@health.wa.gov.au
• Hong Kong
  • Chai Wan, Hong Kong
    • Recruiting
    • Pamela Youde Nethersole Eastern Hospital
  • Wan Chai, Hong Kong
    • Recruiting
    • Ruttonjee Hospital
  • Sha Tin
    • Shatin, Sha Tin, Hong Kong
      • Recruiting
      • North District Hospital
• New Zealand
  • Auckland
    • Auckland, Auckland, New Zealand, 1023
      • Recruiting
      • Auckland City Hospital
  • Middlemore
    • Auckland, Middlemore, New Zealand, 2025
      • Recruiting
      • Middlemore Hospital
  • Waikato Region
    • Hamilton, Waikato Region, New Zealand, 3204
      • Recruiting
      • Waikato Hospital
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Recruiting
    • Belfast City Hospital
  • Bristol, United Kingdom, BS10 5NB
    • Recruiting
    • Southmead Hospital, North Bristol Trust
  • Darlington, United Kingdom, DL3 6HX
    • Completed
    • Darlington Memorial Hospital
  • Dudley, United Kingdom, DY1 2HQ
    • Recruiting
    • Russells Hall Hospital
  • Liverpool, United Kingdom
    • Recruiting
    • Royal Liverpool and Broadgreen Hospitals
  • London, United Kingdom, N19 5NF
    • Recruiting
    • Whittington Hospital
  • London, United Kingdom
    • Recruiting
    • Royal Marsden Hospital - London and Sutton
  • Newcastle upon Tyne, United Kingdom
    • Recruiting
    • Newcastle Upon Tyne Hospitals
  • Norwich, United Kingdom, NR4 7UY
    • Recruiting
    • Norfolk and Norwich University Hospital
  • Rotherham, United Kingdom, S60 2UD
    • Recruiting
    • Rotherham NHS Foundation Trust
  • Sheffield, United Kingdom, S10 2JF
    • Recruiting
    • Royal Hallamshire Hospital
  • Southampton, United Kingdom
    • Recruiting
    • University Hospital Southampton
  • St Helens, United Kingdom, WA9 3DA
    • Recruiting
    • St Helen's Hospital
  • Torquay, United Kingdom, TQ2 7AA
    • Active, not recruiting
    • Torbay Hospital
  • Scotland
    • Wishaw, Scotland, United Kingdom
      • Recruiting
      • University Hospital Wishaw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Consenting adult female patients (≥18 years) undergoing mastectomy (unilateral or bilateral) or breast conserving surgery (unilateral or bilateral) for the primary excision of confirmed or suspected primary breast cancer under general anaesthesia (including those with simultaneous insertion of tissue expanders or implants)*. * this specifically excludes patients undergoing surgery for locoregional recurrence
• American Society of Anaesthesiologist (ASA) physical scale 1-3

Exclusion Criteria:

• Mastectomy or breast conserving surgery with add on procedures e.g laparoscopic salpingectomy
• Where surgery is being performed for locoregional recurrence of breast cancer
• Pre-existing pain at site of surgery, axilla, ipsilateral side of chest wall or the ipsilateral upper arm (at diagnosis prior to any tumor locating procedures)
• Re-excision procedures where the margins at the index surgery have been deemed insufficient
• When immediate autologous reconstruction surgery is planned
• Where delayed autologous reconstruction surgery on the operative breast within one year is planned
• Planned use of regional analgesia infusions
• Impaired cognition
• Pregnant or lactating females
• Transgender patients
• Known metastatic disease
• History of anaphylaxis, sensitivity or known contraindication to lidocaine (or other amide local anaesthetic agents e.g. other amide local anaesthetic agents: ropivacaine, bupivacaine, mepivacaine, prilocaine, etidocaine), including patients with porphyria or methaemoglobinaemia
• History of epilepsy
• Baseline heart rate < 50 bpm or systolic blood pressure < 100mmHg.
• Acute coronary event in the last three months
• Cardiac conduction abnormalities, including; Atrial fibrillation, Heart block (all degrees), Bundle Branch Block or Fascicular block, Prolonged QT interval, Wolf Parkinson White syndrome, channelopathy such as Brugada syndrome. A preoperative Electrocardiogram (ECG) is not mandatory, unless clinically indicated
• Abnormal serum potassium concentration (based upon site laboratory reference ranges)
• Active liver disease e.g. viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, haemochromatosis, other rarer causes)
• Medications within the last 7 days which are known / suspected to slow lidocaine metabolism (amiodarone, beta blockers, cimetidine, fluoroquinolones, fluvoxamine, imidazoles, macrolides, verapamil, HIV drugs)
• Cardiac Failure (any documented heart failure at peroperative assessment or GP records)
• Severe Renal Failure (Creatinine Clearance of less than 30ml/min or dialysis dependent)
• Co-administration of lidocaine within 24 hours prior to surgery for other reasons (e.g. lidocaine patches

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lidocaine; 2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative.	Drug: lidocaine 2% and 10%; Lidocaine infusion: Commencing with an intravenous bolus after induction of anaesthesia, 0.125 ml/kg of lean body weight (LBW) of 2% lidocaine (2.5 mg/kg).*; Followed by a 2% lidocaine intravenous infusion for the duration of surgery, 0.1665 ml/kg/h of LBW (3.33 mg/kg/hr).*; A post-operative subcutaneous 0.0222 ml/kg/hr of LBW 10% lidocaine infusion for up to 24 hours thereafter (2.22 mg/kg/hr). Dosage will be capped at a maximum lean body weight of 68kg.*Day-case surgery receives intraoperative bolus and intraoperative infusion only; Other Names: Xylocaine (lidocaine) 2% and Xylocard (lidocaine) 10%
Placebo Comparator: Placebo; 0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative.	Drug: Placebo; Placebo infusion: Commencing with an intravenous bolus after induction of anaesthesia, 0.125 ml/kg of lean body weight (LBW) of 0.9% Saline solution.*; Followed by a 0.9% Saline solution intravenous infusion for the duration of surgery, 0.1665 ml/kg/h of LBW (3.33 mg/kg/hr).*; A post-operative subcutaneous 0.0222 ml/kg/hr of LBW 0.9% Saline solution infusion for up to 24 hours thereafter (2.22 mg/kg/hr). Dosage will be capped at a maximum lean body weight of 68kg.*Day-case surgery receives intraoperative bolus and intraoperative infusion only; Other Names: 0.9% Saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of moderate or severe CPSP at 1 year after surgery, as reported by the patient at the follow-up review.	Numerical rating scale ≥4 out of 10 for worst pain in the last week - The pain must have been present for at least 3 months prior to the one year assessment (or longer).	1 year post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of acute postoperative pain at rest	Maximum pain score, Numerical rating scale (NRS) 0-10	24 hours postoperatively
Severity of Acute postoperative pain on movement	Maximum pain score, Numerical rating scale (NRS) 0-10	24 hours postoperatively
Postoperative opioid consumption	Morphine Equivalent Opioid Consumption (MEQ)	3 months (last 24-hours)
Postoperative opioid consumption	Morphine Equivalent Opioid Consumption (MEQ)	1 year post surgery (last 24 hours)
Physical functioning	Using interference component of mBPI-SF	1 year post surgery
The incidence of discomfort or altered sensation at the site of surgery (not reported as pain)	Patients asked if they have any altered sensation at the site of surgery	1 year post surgery
Incidence of neuropathic symptoms	Incidence examined as a binary outcome using the Short Form of Douleur Neuropathique 4 Questions (S-DN4)	1 year post surgery
Changes in quality of life metrics EuroQol 5 Dimension 5 Level (EQ-5D-5L) at 1 year after surgery compared to baseline	Changes in the quality of life	1 year post surgery
Changes in psychological wellbeing Kessler Psychological Distress Scale (K-10) at 1 year after surgery compared to baseline.	Changes in psychological wellbeing	1 year post surgery
The incidence of mortality at 1 year	Mortality at 1 year	1 year post surgery
Postoperative opioid consumption	Morphine Equivalent Opioid Consumption (MEQ)	on Day 1
The incidence of severe CPSP at 1 year after surgery	NRS for worst pain the in the last week of ≥7)	1 year post surgery
UK NHS costs of care over 1 year following surgery	UK/NHS sites only	1 year post surgery
Productivity costs over 1 year following surgery	UK/NHS sites only	1 year post surgery
Quality-adjusted life years (QALYs) over 1 year following surgery	UK/NHS sites only	1 year post surgery
Cost-effectiveness of perioperative lidocaine infusions compared to usual care, from a primary UK NHS perspective and broader perspective including productivity, at 1 year.	UK/NHS sites only	1 year post surgery
Severity of pain at the site of surgery	Assessed using "average" and "worst" NRS pain score in the last week, obtained from the adapted modified Brief Pain Inventory-Short Form (mBPI-SF)	1 year post surgery
The incidence of mild or greater pain at the site of surgery at 1 year after surgery	NRS for worst pain the in the last week of ≥1	1 year post surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treated bradycardia intraoperatively	Drug related safety Endpoints	24 hours postoperatively
Incidence of treated bradycardia in Post Anaesthesia Care Unit (PACU)	Drug related safety Endpoints	24 hours postoperatively
Incidence of treated hypotension intraoperatively	Drug related safety Endpoints	24 hours postoperatively
Incidence of treated hypotension in Post Anaesthesia Care Unit (PACU)	Drug related safety Endpoints	24 hours postoperatively
Incidence of Medical Emergency Team (MET) activation	Drug related safety Endpoints	24 hours postoperatively
Incidence of unplanned Intensive Care Unit (ICU), High Dependency Unit (HDU) or Critical Care Unit (CCU) admission	Drug related safety Endpoints	24 hours postoperatively
Incidence of intraoperative infusion stopping events	Drug related safety Endpoints	24 hours postoperatively
Incidence of Post Anaesthesia Care Unit (PACU) infusion stopping events	Drug related safety Endpoints, (x2 symptoms, x1 sign, x1 complication)	24 hours postoperatively
Incidence of suspected lidocaine toxicity events	Drug related safety Endpoints	24 hours postoperatively
Incidence of study drug unblinding events	Drug related safety Endpoints	24 hours postoperatively
Incidence of subcutaneous catheter site events	Drug related safety Endpoints	Day 30
Incidence of postoperative infusion stopping events on the ward	Drug related safety Endpoints, (x2 symptoms, x1 sign, x1 complication)	24 hours postoperatively
Incidence of suspected SEVERE lidocaine toxicity events	Drug related safety Endpoints, (generalised seizure, sudden unexplained LOC, life-threatening arrhythmia, or asystole, cardiac or circulatory arrest)	24 hours postoperatively

Collaborators and Investigators

• Sponsor: Monash University
• Collaborators: Royal Perth Hospital
• Investigators: Principal Investigator: Tomas Corcoran, Royal Perth Hospital

Publications and helpful links

General Publications

• Toner AJ, Bailey MA, Schug SA, Corcoran TB. A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery. Anaesthesia. 2021 Oct;76(10):1326-1341. doi: 10.1111/anae.15440. Epub 2021 Mar 2.
• Toner AJ, Bailey MA, Schug SA, Phillips M, Ungerer JP, Somogyi AA, Corcoran TB. Serum lidocaine (lignocaine) concentrations during prolonged perioperative infusion in patients undergoing breast cancer surgery: A secondary analysis of a randomised controlled trial. Anaesth Intensive Care. 2023 Nov;51(6):422-431. doi: 10.1177/0310057X231194833. Epub 2023 Oct 6.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: October 3, 2021
• First Submitted That Met QC Criteria: October 3, 2021
• First Posted (Actual): October 8, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 22, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Anaesthesia; Local Anaesthesia; Chronic Post Surgical Pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Pain, Postoperative; Breast Neoplasms; Organic Chemicals; Pharmaceutical Preparations; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Crystalloid Solutions; Isotonic Solutions; Solutions; Lidocaine; Saline Solution
• Other Study ID Numbers: HREC/74777/Alfred-2021

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