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

Sponsor

Monash University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05072314

Collaborator

Royal Perth Hospital (Other)

4,300

Enrollment

Arms

67.1

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Breast Cancer Female Breast Conserving Surgery Mastectomy	Drug: lidocaine 2% and 10% Drug: Placebo	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

4300 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes 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.

Primary Purpose:

Prevention

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2027

Anticipated Study Completion Date :

Feb 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lidocaine 2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative.	Drug: lidocaine 2% and 10% Lidocaine infusion: Commencing with an intravenous bolus after induction of anaesthesia (2.5 mg/kg), Followed by a 2% lidocaine intravenous infusion for the duration of surgery (3.33 mg/kg/hr) A post-operative subcutaneous 10% lidocaine infusion for up to 24 hours thereafter (2.22 mg/kg/hr). Other Names: Xylocaine (lidocaine) 2% and Xylocard (lidocaine) 10%
Placebo Comparator: Placebo 0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative.	Drug: Placebo Saline infusion: Commencing with an intravenous bolus after induction of anaesthesia (2.5 mg/kg), Followed by a 2% lidocaine intravenous infusion for the duration of surgery (3.33 mg/kg/hr) A post-operative subcutaneous 10% lidocaine infusion for up to 24 hours thereafter (2.22 mg/kg/hr). Other Names: 0.9% Saline solution

Arm

Intervention/Treatment

Active Comparator: Lidocaine

2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative.

Drug: lidocaine 2% and 10%

Lidocaine infusion: Commencing with an intravenous bolus after induction of anaesthesia (2.5 mg/kg), Followed by a 2% lidocaine intravenous infusion for the duration of surgery (3.33 mg/kg/hr) A post-operative subcutaneous 10% lidocaine infusion for up to 24 hours thereafter (2.22 mg/kg/hr).

Other Names:

Xylocaine (lidocaine) 2% and Xylocard (lidocaine) 10%

Placebo Comparator: Placebo

0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative.

Drug: Placebo

Saline infusion: Commencing with an intravenous bolus after induction of anaesthesia (2.5 mg/kg), Followed by a 2% lidocaine intravenous infusion for the duration of surgery (3.33 mg/kg/hr) A post-operative subcutaneous 10% lidocaine infusion for up to 24 hours thereafter (2.22 mg/kg/hr).

Other Names:

0.9% Saline solution

Outcome Measures

Primary Outcome Measures

The incidence of moderate or severe CPSP related to the site of surgery at 1 year after surgery [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

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 [24 hours postoperatively]
Morphine Equivalent Opioid Consumption (MEQ)
Postoperative opioid consumption [3 months (last 24-hours)]
Morphine Equivalent Opioid Consumption (MEQ)
The incidence of severe CPSP related to the site of surgery at 1 year after surgery [1 year post 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 [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]
Severity of CPSP [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 Neuropathic Pain Questionnaire (NPQ)
Postoperative opioid consumption [1 year post surgery (last 24 hours)]
Morphine Equivalent Opioid Consumption (MEQ)
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 psychological wellbeing Kessler Psychological Distress Scale (K-10) at 1 year after surgery compared to baseline. [1 year post surgery]
The incidence of mortality at 1 year [1 year post surgery]

Other Outcome Measures

Incidence of treated bradycardia intraoperatively [24 hours postoperatively]
Drug related safety Endpoints
Incidence of treated bradycardia in Post Anaesthesia Care Unit (PACU) [24 hours postoperatively]
Drug related safety Endpoints
Incidence of treated hypotension intraoperatively [24 hours postoperatively]
Drug related safety Endpoints
Incidence of treated hypotension in Post Anaesthesia Care Unit (PACU) [24 hours postoperatively]
Drug related safety Endpoints
Incidence of Medical Emergency Team (MET) activation [24 hours postoperatively]
Drug related safety Endpoints
Incidence of unplanned Intensive Care Unit (ICU), High Dependency Unit (HDU) or Critical Care Unit (CCU) admission [24 hours postoperatively]
Drug related safety Endpoints
Incidence of intraoperative infusion stopping events [24 hours postoperatively]
Drug related safety Endpoints
Incidence of Post Anaesthesia Care Unit (PACU) infusion stopping events [24 hours postoperatively]
Drug related safety Endpoints, (x2 symptoms, x1 sign)
Incidence of postoperative infusion stopping events [24 hours postoperatively]
Drug related safety Endpoints, (x2 symptoms, x1 sign)
Incidence of suspected lidocaine toxicity events [24 hours postoperatively]
Drug related safety Endpoints
Incidence of suspected SEVERE local anaesthetic toxicity events [24 hours postoperatively]
Drug related safety Endpoints, (generalised seizure, life-threatening arrhythmia, sudden unexplained loss of consciousness)
Incidence of study drug unblinding events [24 hours postoperatively]
Drug related safety Endpoints
Incidence of subcutaneous catheter site events [24 hours postoperatively]
Drug related safety Endpoints

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Consenting adult female patients (≥18 years, <80 years) undergoing mastectomy or 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