Clinical trial NCT05072314: Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial
Official title: Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Breast Cancer Female
Breast Conserving Surgery
Mastectomy
Keywords: Anaesthesia
Local Anaesthesia
Chronic Post Surgical Pain
Lead sponsor: Monash University
Sponsor class: OTHER
Collaborators: name: Royal Perth Hospital
First posted: 2021-10-08
Enrollment: 4300
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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 \&lt; 50 bpm or systolic blood pressure \&lt; 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

Primary outcomes:
measure: The incidence of moderate or severe CPSP at 1 year after surgery, as reported by the patient at the follow-up review.
timeFrame: 1 year post-surgery
Secondary outcomes:
measure: Severity of acute postoperative pain at rest
timeFrame: 24 hours postoperatively
measure: Severity of Acute postoperative pain on movement
timeFrame: 24 hours postoperatively
measure: Postoperative opioid consumption
timeFrame: on Day 1
measure: Postoperative opioid consumption
timeFrame: 3 months (last 24-hours)
measure: The Incidence of moderate to severe Chronic Post Surgical Pain from radiation therapy
timeFrame: 1 year post surgery
measure: The Incidence of moderate to severe Chronic Post Surgical Pain from repeat surgery
timeFrame: 1 year post surgery
measure: The incidence of severe CPSP at 1 year after surgery
timeFrame: 1 year post surgery
measure: The incidence of mild or greater CPSP at 1 year after surgery
timeFrame: 1 year post surgery
measure: The incidence of discomfort or altered sensation at the site of surgery (not reported as pain)
timeFrame: 1 year post surgery
measure: Severity of CPSP
timeFrame: 1 year post surgery
measure: Incidence of neuropathic symptoms
timeFrame: 1 year post surgery
measure: Postoperative opioid consumption
timeFrame: 1 year post surgery (last 24 hours)
measure: Physical functioning
timeFrame: 1 year post surgery
measure: Changes in quality of life metrics EuroQol 5 Dimension 5 Level (EQ-5D-5L) at 1 year after surgery compared to baseline
timeFrame: 1 year post surgery
measure: Changes in psychological wellbeing Kessler Psychological Distress Scale (K-10) at 1 year after surgery compared to baseline.
timeFrame: 1 year post surgery
measure: The incidence of mortality at 1 year
timeFrame: 1 year post surgery
measure: UK NHS costs of care over 1 year following surgery
timeFrame: 1 year post surgery
measure: Productivity costs over 1 year following surgery
timeFrame: 1 year post surgery
measure: Quality-adjusted life years (QALYs) over 1 year following surgery
timeFrame: 1 year post surgery
measure: Cost-effectiveness of perioperative lidocaine infusions compared to usual care, from a primary UK NHS perspective and broader perspective including productivity, at 1 year.
timeFrame: 1 year post surgery
Other outcomes:
measure: Incidence of treated bradycardia intraoperatively
timeFrame: 24 hours postoperatively
measure: Incidence of treated hypotension intraoperatively
timeFrame: 24 hours postoperatively
measure: Incidence of treated bradycardia in Post Anaesthesia Care Unit (PACU)
timeFrame: 24 hours postoperatively
measure: Incidence of treated hypotension in Post Anaesthesia Care Unit (PACU)
timeFrame: 24 hours postoperatively
measure: Incidence of intraoperative infusion stopping events
timeFrame: 24 hours postoperatively
measure: Incidence of Post Anaesthesia Care Unit (PACU) infusion stopping events
timeFrame: 24 hours postoperatively
measure: Incidence of postoperative infusion stopping events on the ward
timeFrame: 24 hours postoperatively
measure: Incidence of suspected lidocaine toxicity events
timeFrame: 24 hours postoperatively
measure: Incidence of suspected SEVERE local anaesthetic toxicity events
timeFrame: 24 hours postoperatively
measure: Incidence of Medical Emergency Team (MET) activation
timeFrame: 24 hours postoperatively
measure: Incidence of unplanned Intensive Care Unit (ICU), High Dependency Unit (HDU) or Critical Care Unit (CCU) admission
timeFrame: 24 hours postoperatively
measure: Incidence of study drug unblinding events
timeFrame: 24 hours postoperatively
measure: Incidence of subcutaneous catheter site events
timeFrame: Day 30
Locations:
city: Blacktown/Mt Druitt
country: Australia
facility: Blacktown Mount Druitt Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Sydney
country: Australia
facility: St George Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Coopers Plains
country: Australia
facility: Queen Elizabeth II Jubilee Hospital
state: Queensland
city: Mackay
country: Australia
facility: Mackay Base Hospital
state: Queensland
city: Rockhampton
country: Australia
facility: Rockhampton Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast Hospital and Health Service- Gold Coast University Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Bedford Park
country: Australia
facility: Flinders Medical Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Ballarat
country: Australia
facility: Anaesthetic Group Ballarat
state: Victoria
city: Ballarat
country: Australia
facility: Ballarat Health Services (Grampians Health)
state: Victoria
city: Geelong
country: Australia
facility: Barwon Health - University Hospital Geelong
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred
state: Victoria
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne
state: Victoria
city: Melbourne
country: Australia
facility: Northern Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Monash Health - Moorabbin Hospital
state: Victoria
city: Ringwood East
country: Australia
facility: Maroondah Hospital - Eastern Health
state: Victoria
city: Shepparton
country: Australia
facility: Goulburn Valley Health
state: Victoria
city: Traralgon
country: Australia
facility: Latrobe Regional Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Perth
country: Australia
facility: St John of God Subiaco
state: Western Australia
city: Chai Wan
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Sha Tin
country: Hong Kong
facility: North District Hospital
city: Wan Chai
country: Hong Kong
facility: Ruttonjee Hospital
city: Auckland
country: New Zealand
facility: Middlemore Hospital
state: Middlemore
city: Hamilton
country: New Zealand
facility: Waikato Hospital
state: Waikato
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Wishaw
country: United Kingdom
facility: University Hospital Wishaw
state: Scotland
city: Bristol
country: United Kingdom
facility: Southmead Hospital, North Bristol Trust
city: Darlington
country: United Kingdom
facility: Darlington Memorial Hospital
city: Liverpool
country: United Kingdom
facility: Royal Liverpool and Broadgreen Hospitals
city: Rotherham
country: United Kingdom
facility: Rotherham NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: University Hospital Southampton
Study officials:
affiliation: Royal Perth Hospital
name: Tomas Corcoran
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.