Back to resultsLong-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial (LOLIPOP)
Primary Purpose
Breast Cancer, Breast Cancer Female, Breast Conserving Surgery
Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
lidocaine 2% and 10%
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Breast Cancer focused on measuring Anaesthesia, Local Anaesthesia, Chronic Post Surgical Pain
Eligibility Criteria
Inclusion Criteria:
- Consenting adult female patients (≥18 years, <80 years) undergoing unilateral mastectomy or unilateral breast conserving surgery 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 or deemed likely
- Bilateral procedures
- Planned use of regional analgesia infusions
- Inability to communicate in English
- 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; 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.
- 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)
- Abnormal liver function tests (based upon site laboratory reference ranges)
- 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
Sites / Locations
- Prince of Wales Hospital
- Royal North Shore HospitalRecruiting
- Westmead HospitalRecruiting
- St George Hospital
- Royal Brisbane and Women's HospitalRecruiting
- Queen Elizabeth II Jubilee HospitalRecruiting
- Mackay Base HospitalRecruiting
- Rockhampton HospitalRecruiting
- Gold Coast Hospital and Health Service- Gold Coast University HospitalRecruiting
- Princess Alexandra HospitalRecruiting
- Flinders Medical Centre
- Royal Hobart HospitalRecruiting
- Anaesthetic Group BallaratRecruiting
- Ballarat Health Services (Grampians Health)Recruiting
- Barwon Health - University Hospital GeelongRecruiting
- The AlfredRecruiting
- Royal Melbourne HospitalRecruiting
- St Vincent's Hospital Melbourne
- Northern Hospital
- Monash Health - Moorabbin Hospital
- Maroondah Hospital - Eastern HealthRecruiting
- Goulburn Valley HealthRecruiting
- Latrobe Regional Hospital
- Royal Perth HospitalRecruiting
- St John of God SubiacoRecruiting
- Prince of Wales HospitalRecruiting
- Waikato Hospital
- Auckland City HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Lidocaine
Placebo
Arm Description
2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative.
0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
Severity of acute postoperative pain at rest
Maximum pain score, Numerical rating scale (NRS) 0-10
Severity of Acute postoperative pain on movement
Maximum pain score, Numerical rating scale (NRS) 0-10
Postoperative opioid consumption
Morphine Equivalent Opioid Consumption (MEQ)
Postoperative opioid consumption
Morphine Equivalent Opioid Consumption (MEQ)
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)
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
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
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)
Incidence of neuropathic symptoms
Incidence examined as a binary outcome using the Short Form of Douleur Neuropathique 4 Questions (S-DN4)
Postoperative opioid consumption
Morphine Equivalent Opioid Consumption (MEQ)
Physical functioning
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
Changes in the quality of life
Changes in psychological wellbeing Kessler Psychological Distress Scale (K-10) at 1 year after surgery compared to baseline.
Changes in psychological wellbeing
The incidence of mortality at 1 year
Mortality at 1 year
Full Information
NCT ID
NCT05072314
First Posted
October 3, 2021
Last Updated
July 11, 2023
Sponsor
Monash University
Collaborators
Royal Perth Hospital
1. Study Identification
Unique Protocol Identification Number
NCT05072314
Brief Title
Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial
Acronym
LOLIPOP
Official Title
Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 27, 2022 (Actual)
Primary Completion Date
July 2027 (Anticipated)
Study Completion Date
July 2028 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Monash University
Collaborators
Royal Perth Hospital
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Breast Cancer Female, Breast Conserving Surgery, Mastectomy
Keywords
Anaesthesia, Local Anaesthesia, Chronic Post Surgical Pain
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All trial participants, research coordinators, members of the anaesthesia and surgical teams, pharmacists, theatre and ward staff and all individuals performing patient follow up will be blinded to the patient's treatment allocation. All of the trial committees associated with the study will be blinded, with the exception of the Data Safety and Monitoring Committee (DSMC), who will receive unblinded (open) reports from the independent statistician. Unblinding of the patient's treatment allocation will be possible in exceptional circumstances, and a process will be in place to facilitate unblinding requests.
Allocation
Randomized
Enrollment
4300 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Lidocaine
Arm Type
Active Comparator
Arm Description
2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative.
Intervention Type
Drug
Intervention Name(s)
lidocaine 2% and 10%
Other Intervention Name(s)
Xylocaine (lidocaine) 2% and Xylocard (lidocaine) 10%
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
0.9% Saline solution
Intervention Description
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.
Primary Outcome Measure Information:
Title
The incidence of moderate or severe CPSP related to the site of surgery at 1 year after surgery
Description
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).
Time Frame
1 year post-surgery
Secondary Outcome Measure Information:
Title
Severity of acute postoperative pain at rest
Description
Maximum pain score, Numerical rating scale (NRS) 0-10
Time Frame
24 hours postoperatively
Title
Severity of Acute postoperative pain on movement
Description
Maximum pain score, Numerical rating scale (NRS) 0-10
Time Frame
24 hours postoperatively
Title
Postoperative opioid consumption
Description
Morphine Equivalent Opioid Consumption (MEQ)
Time Frame
24 hours postoperatively
Title
Postoperative opioid consumption
Description
Morphine Equivalent Opioid Consumption (MEQ)
Time Frame
3 months (last 24-hours)
Title
The incidence of severe CPSP related to the site of surgery at 1 year after surgery
Description
NRS for worst pain the in the last week of ≥7)
Time Frame
1 year post surgery
Title
The incidence of mild or greater CPSP related to the site of surgery at 1 year after surgery
Description
NRS for worst pain the in the last week of ≥1
Time Frame
1 year post surgery
Title
The incidence of discomfort or altered sensation at the site of surgery (not reported as pain)
Description
Patients asked if they have any altered sensation at the site of surgery
Time Frame
1 year post surgery
Title
Severity of CPSP
Description
Assessed using "average" and "worst" NRS pain score in the last week, obtained from the adapted modified Brief Pain Inventory-Short Form (mBPI-SF)
Time Frame
1 year post surgery
Title
Incidence of neuropathic symptoms
Description
Incidence examined as a binary outcome using the Short Form of Douleur Neuropathique 4 Questions (S-DN4)
Time Frame
1 year post surgery
Title
Postoperative opioid consumption
Description
Morphine Equivalent Opioid Consumption (MEQ)
Time Frame
1 year post surgery (last 24 hours)
Title
Physical functioning
Description
Using interference component of mBPI-SF
Time Frame
1 year post surgery
Title
Changes in quality of life metrics EuroQol 5 Dimension 5 Level (EQ-5D-5L) at 1 year after surgery compared to baseline
Description
Changes in the quality of life
Time Frame
1 year post surgery
Title
Changes in psychological wellbeing Kessler Psychological Distress Scale (K-10) at 1 year after surgery compared to baseline.
Description
Changes in psychological wellbeing
Time Frame
1 year post surgery
Title
The incidence of mortality at 1 year
Description
Mortality at 1 year
Time Frame
1 year post surgery
Other Pre-specified Outcome Measures:
Title
Incidence of treated bradycardia intraoperatively
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of treated bradycardia in Post Anaesthesia Care Unit (PACU)
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of treated hypotension intraoperatively
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of treated hypotension in Post Anaesthesia Care Unit (PACU)
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of Medical Emergency Team (MET) activation
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of unplanned Intensive Care Unit (ICU), High Dependency Unit (HDU) or Critical Care Unit (CCU) admission
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of intraoperative infusion stopping events
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of Post Anaesthesia Care Unit (PACU) infusion stopping events
Description
Drug related safety Endpoints, (x2 symptoms, x1 sign, x1 complication)
Time Frame
24 hours postoperatively
Title
Incidence of postoperative infusion stopping events
Description
Drug related safety Endpoints, (x2 symptoms, x1 sign, x1 complication)
Time Frame
24 hours postoperatively
Title
Incidence of suspected lidocaine toxicity events
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of suspected SEVERE local anaesthetic toxicity events
Description
Drug related safety Endpoints, (generalised seizure, sudden unexplained LOC, life-threatening arrhythmia, or asystole, cardiac or circulatory arrest)
Time Frame
24 hours postoperatively
Title
Incidence of study drug unblinding events
Description
Drug related safety Endpoints
Time Frame
24 hours postoperatively
Title
Incidence of subcutaneous catheter site events
Description
Drug related safety Endpoints
Time Frame
Day 30
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 < 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)
Abnormal liver function tests (based upon site laboratory reference ranges)
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gillian Ormond
Phone
+61 (03) 9903 0387
Email
gillian.ormond@monash.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Natalie Hird
Phone
+ 61 (0) 459 407 231
Email
natalie.hird@health.wa.gov.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tomas Corcoran
Organizational Affiliation
Royal Perth Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Prince of Wales Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2031
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Royal North Shore Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2035
Country
Australia
Individual Site Status
Recruiting
Facility Name
Westmead Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Recruiting
Facility Name
St George Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2217
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Royal Brisbane and Women's Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Individual Site Status
Recruiting
Facility Name
Queen Elizabeth II Jubilee Hospital
City
Coopers Plains
State/Province
Queensland
ZIP/Postal Code
4108
Country
Australia
Individual Site Status
Recruiting
Facility Name
Mackay Base Hospital
City
Mackay
State/Province
Queensland
ZIP/Postal Code
4740
Country
Australia
Individual Site Status
Recruiting
Facility Name
Rockhampton Hospital
City
Rockhampton
State/Province
Queensland
ZIP/Postal Code
4700
Country
Australia
Individual Site Status
Recruiting
Facility Name
Gold Coast Hospital and Health Service- Gold Coast University Hospital
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Individual Site Status
Recruiting
Facility Name
Princess Alexandra Hospital
City
Woolloongabba
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Individual Site Status
Recruiting
Facility Name
Flinders Medical Centre
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Royal Hobart Hospital
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Individual Site Status
Recruiting
Facility Name
Anaesthetic Group Ballarat
City
Ballarat
State/Province
Victoria
ZIP/Postal Code
3350
Country
Australia
Individual Site Status
Recruiting
Facility Name
Ballarat Health Services (Grampians Health)
City
Ballarat
State/Province
Victoria
ZIP/Postal Code
3350
Country
Australia
Individual Site Status
Recruiting
Facility Name
Barwon Health - University Hospital Geelong
City
Geelong
State/Province
Victoria
ZIP/Postal Code
3220
Country
Australia
Individual Site Status
Recruiting
Facility Name
The Alfred
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Name
Royal Melbourne Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Individual Site Status
Recruiting
Facility Name
St Vincent's Hospital Melbourne
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Northern Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3076
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Monash Health - Moorabbin Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3165
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Maroondah Hospital - Eastern Health
City
Ringwood East
State/Province
Victoria
ZIP/Postal Code
3135
Country
Australia
Individual Site Status
Recruiting
Facility Name
Goulburn Valley Health
City
Shepparton
State/Province
Victoria
ZIP/Postal Code
3630
Country
Australia
Individual Site Status
Recruiting
Facility Name
Latrobe Regional Hospital
City
Traralgon
State/Province
Victoria
ZIP/Postal Code
3844
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Royal Perth Hospital
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Individual Site Status
Recruiting
Facility Name
St John of God Subiaco
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6008
Country
Australia
Individual Site Status
Recruiting
Facility Name
Prince of Wales Hospital
City
Sha Tin
Country
Hong Kong
Individual Site Status
Recruiting
Facility Name
Waikato Hospital
City
Hamilton
State/Province
Waikato
ZIP/Postal Code
3204
Country
New Zealand
Individual Site Status
Not yet recruiting
Facility Name
Auckland City Hospital
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33651896
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.
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Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial
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