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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
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.

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 breast cancer under general anaesthesia (including those with simultaneous insertion of tissue expanders or implants).
  • American Society of Anaesthesiologist (ASA) physical scale 1-3
Exclusion Criteria
  • Pre-existing pain at site of surgery, axilla, ipsilateral side of chest wall or the ipsilateral upper arm
  • 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)
  • Abnormal serum sodium 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
GroupInterventionDescription
Lidocainelidocaine 2% and 10%2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative.
PlaceboPlacebo0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative.
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Severity of acute postoperative pain at rest24 hours postoperatively

Maximum pain score, Numerical rating scale (NRS) 0-10

Severity of Acute postoperative pain on movement24 hours postoperatively

Maximum pain score, Numerical rating scale (NRS) 0-10

Postoperative opioid consumption1 year post surgery (last 24 hours)

Morphine Equivalent Opioid Consumption (MEQ)

The Incidence of moderate to severe Chronic Post Surgical Pain from radiation therapy1 year post surgery

with a significant contribution from radiation therapy

The Incidence of moderate to severe Chronic Post Surgical Pain from repeat surgery1 year post surgery

with a significant contribution from repeat surgery

The incidence of severe CPSP at 1 year after surgery1 year post surgery

NRS for worst pain the in the last week of ≥7)

The incidence of mild or greater CPSP at 1 year after surgery1 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 CPSP1 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 symptoms1 year post surgery

Incidence examined as a binary outcome using the Short Form of Douleur Neuropathique 4 Questions (S-DN4)

Physical functioning1 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 baseline1 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 mortality at 1 year1 year post surgery

Mortality at 1 year

UK NHS costs of care over 1 year following surgery1 year post surgery

UK/NHS sites only

Productivity costs over 1 year following surgery1 year post surgery

UK/NHS sites only

Quality-adjusted life years (QALYs) over 1 year following surgery1 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 (37)

Blacktown Mount Druitt Hospital

🇦🇺

Blacktown/Mt 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

Flinders Medical Centre

🇦🇺

Bedford Park, South Australia, Australia

Royal Hobart Hospital

🇦🇺

Hobart, Tasmania, Australia

Anaesthetic Group Ballarat

🇦🇺

Ballarat, Victoria, Australia

Ballarat Health Services (Grampians Health)

🇦🇺

Ballarat, Victoria, Australia

Barwon Health - University Hospital Geelong

🇦🇺

Geelong, Victoria, Australia

The Alfred

🇦🇺

Melbourne, Victoria, Australia

Royal Melbourne Hospital

🇦🇺

Melbourne, Victoria, Australia

St Vincent's Hospital Melbourne

🇦🇺

Melbourne, Victoria, Australia

Northern Hospital

🇦🇺

Melbourne, Victoria, Australia

Monash Health - Moorabbin Hospital

🇦🇺

Melbourne, Victoria, Australia

Maroondah Hospital - Eastern Health

🇦🇺

Ringwood East, Victoria, Australia

Goulburn Valley Health

🇦🇺

Shepparton, Victoria, Australia

Latrobe Regional Hospital

🇦🇺

Traralgon, Victoria, Australia

Royal Perth Hospital

🇦🇺

Perth, Western Australia, Australia

St John of God Subiaco

🇦🇺

Perth, Western Australia, Australia

Pamela Youde Nethersole Eastern Hospital

🇭🇰

Chai Wan, Hong Kong

North District Hospital

🇭🇰

Sha Tin, Hong Kong

Ruttonjee Hospital

🇭🇰

Wan Chai, Hong Kong

Middlemore Hospital

🇳🇿

Auckland, Middlemore, New Zealand

Waikato Hospital

🇳🇿

Hamilton, Waikato, New Zealand

Auckland City Hospital

🇳🇿

Auckland, New Zealand

University Hospital Wishaw

🇬🇧

Wishaw, Scotland, United Kingdom

Southmead Hospital, North Bristol Trust

🇬🇧

Bristol, United Kingdom

Darlington Memorial Hospital

🇬🇧

Darlington, United Kingdom

Royal Liverpool and Broadgreen Hospitals

🇬🇧

Liverpool, United Kingdom

Rotherham NHS Foundation Trust

🇬🇧

Rotherham, United Kingdom

University Hospital Southampton

🇬🇧

Southampton, United Kingdom

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