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

Breast Cancer Clinical Trial

— LOLIPOP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05072314
• Other study ID #: HREC/74777/Alfred-2021
• Status: Recruiting
• Phase: Phase 4
• Start date: July 27, 2022
• Est. completion date: July 2028

Study information

• Verified date: February 2024
• Source: Monash University
• Contact: Gillian Ormond
• Phone: +61 (03) 9903 0387
• Email: gillian.ormond[@]monash.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 4300
• Est. completion date: July 2028
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

• 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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Cancer Female
• Breast Conserving Surgery
• Breast Neoplasms
• Mastectomy
• Pain, Postoperative

Intervention

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
• 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

Locations

Country	Name	City	State
Australia	Anaesthetic Group Ballarat	Ballarat	Victoria
Australia	Ballarat Health Services (Grampians Health)	Ballarat	Victoria
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Queen Elizabeth II Jubilee Hospital	Coopers Plains	Queensland
Australia	Barwon Health - University Hospital Geelong	Geelong	Victoria
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Mackay Base Hospital	Mackay	Queensland
Australia	Monash Health - Moorabbin Hospital	Melbourne	Victoria
Australia	Northern Hospital	Melbourne	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Australia	St Vincent's Hospital Melbourne	Melbourne	Victoria
Australia	The Alfred	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	St John of God Subiaco	Perth	Western Australia
Australia	Maroondah Hospital - Eastern Health	Ringwood East	Victoria
Australia	Rockhampton Hospital	Rockhampton	Queensland
Australia	Goulburn Valley Health	Shepparton	Victoria
Australia	Gold Coast Hospital and Health Service- Gold Coast University Hospital	Southport	Queensland
Australia	Prince of Wales Hospital	Sydney	New South Wales
Australia	Royal North Shore Hospital	Sydney	New South Wales
Australia	St George Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Sydney	New South Wales
Australia	Latrobe Regional Hospital	Traralgon	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Hong Kong	Pamela Youde Nethersole Eastern Hospital	Chai Wan
Hong Kong	North District Hospital	Sha Tin
Hong Kong	Ruttonjee Hospital	Wan Chai
New Zealand	Auckland City Hospital	Auckland
New Zealand	Waikato Hospital	Hamilton	Waikato

Sponsors (2)

Lead Sponsor	Collaborator
Monash University	Royal Perth Hospital

Countries where clinical trial is conducted

Australia,  Hong Kong,  New Zealand, 

References & Publications (2)

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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of treated bradycardia intraoperatively	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of treated hypotension intraoperatively	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of treated bradycardia in Post Anaesthesia Care Unit (PACU)	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of treated hypotension in Post Anaesthesia Care Unit (PACU)	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of intraoperative infusion stopping events	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of Post Anaesthesia Care Unit (PACU) infusion stopping events	Drug related safety Endpoints, (x2 symptoms, x1 sign, x1 complication)	24 hours postoperatively
Other	Incidence of postoperative infusion stopping events	Drug related safety Endpoints, (x2 symptoms, x1 sign, x1 complication)	24 hours postoperatively
Other	Incidence of suspected lidocaine toxicity events	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of suspected SEVERE local anaesthetic toxicity events	Drug related safety Endpoints, (generalised seizure, sudden unexplained LOC, life-threatening arrhythmia, or asystole, cardiac or circulatory arrest)	24 hours postoperatively
Other	Incidence of Medical Emergency Team (MET) activation	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of unplanned Intensive Care Unit (ICU), High Dependency Unit (HDU) or Critical Care Unit (CCU) admission	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of study drug unblinding events	Drug related safety Endpoints	24 hours postoperatively
Other	Incidence of subcutaneous catheter site events	Drug related safety Endpoints	Day 30
Primary	The incidence of moderate or severe CPSP related to the site of surgery at 1 year after 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).	1 year post-surgery
Secondary	Severity of acute postoperative pain at rest	Maximum pain score, Numerical rating scale (NRS) 0-10	24 hours postoperatively
Secondary	Severity of Acute postoperative pain on movement	Maximum pain score, Numerical rating scale (NRS) 0-10	24 hours postoperatively
Secondary	Postoperative opioid consumption	Morphine Equivalent Opioid Consumption (MEQ)	24 hours postoperatively
Secondary	The incidence of severe CPSP related to the site of surgery at 1 year after surgery	NRS for worst pain the in the last week of =7)	1 year post surgery
Secondary	The incidence of mild or greater CPSP related to the site of surgery at 1 year after surgery	NRS for worst pain the in the last week of =1	1 year post surgery
Secondary	Postoperative opioid consumption	Morphine Equivalent Opioid Consumption (MEQ)	3 months (last 24-hours)
Secondary	The Incidence of moderate to severe Chronic Post Cancer Treatment Pain	Patients asked if they have moderate to severe chronic post cancer treatment pain	1 year post surgery
Secondary	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
Secondary	Severity of CPSP	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
Secondary	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
Secondary	Postoperative opioid consumption	Morphine Equivalent Opioid Consumption (MEQ)	1 year post surgery (last 24 hours)
Secondary	Physical functioning	Using interference component of mBPI-SF	1 year post surgery
Secondary	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
Secondary	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
Secondary	The incidence of mortality at 1 year	Mortality at 1 year	1 year post surgery