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

Phase 3

Recruiting

• Conditions: Breast Cancer; Breast Cancer Female; Breast Conserving Surgery; Mastectomy
• Interventions: Drug: lidocaine 2% and 10%; Drug: Placebo

• Registration Number: NCT05072314
• Lead Sponsor: Monash University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-10-03
• Study First Submitted QC: 2021-10-03
• Study First Posted: 2021-10-08
• Study Start: 2022-07-27
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-03
• Last Update Posted: 2025-07-08
• Primary Completion: 2027-07
• Study Completion: 2028-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 4300

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lidocaine	lidocaine 2% and 10%	2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative.
Placebo	Placebo	0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative.

Primary Outcome Measures

Name	Time	Method
The incidence of moderate or severe CPSP at 1 year after surgery, as reported by the patient at the follow-up review.	1 year post-surgery	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).

Secondary Outcome Measures

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

Trial Locations

Locations (39)

Blacktown Mount Druitt Hospital; 🇦🇺 Mount Druitt, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 Sydney, New South Wales, Australia

Westmead Hospital; 🇦🇺 Sydney, New South Wales, Australia

St George Hospital; 🇦🇺 Sydney, New South Wales, Australia

Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Queen Elizabeth II Jubilee Hospital; 🇦🇺 Coopers Plains, Queensland, Australia

Mackay Base Hospital; 🇦🇺 Mackay, Queensland, Australia

Rockhampton Hospital; 🇦🇺 Rockhampton, Queensland, Australia

Gold Coast Hospital and Health Service- Gold Coast University Hospital; 🇦🇺 Southport, Queensland, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

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