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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Breast Cancer, Breast Cancer Female, Breast Conserving Surgery, Mastectomy

Intervention / Treatment
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* Drug: lidocaine 2% and 10%
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lidocaine<br>2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative. | Drug: lidocaine 2% and 10%<br>* 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.<br>* Other names: Xylocaine (lidocaine) 2% and Xylocard (lidocaine) 10%;|
| Placebo Comparator: Placebo<br>0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative. | Drug: Placebo<br>* 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.<br>* Other names: 0.9% Saline solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of acute postoperative pain at rest | Maximum pain score, Numerical rating scale (NRS) 0-10 | 24 hours postoperatively | 
| Severity of Acute postoperative pain on movement | Maximum pain score, Numerical rating scale (NRS) 0-10 | 24 hours postoperatively | 
| Postoperative opioid consumption | Morphine Equivalent Opioid Consumption (MEQ) | 24 hours postoperatively | 
| Postoperative opioid consumption | Morphine Equivalent Opioid Consumption (MEQ) | 3 months (last 24-hours) | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Postoperative opioid consumption | Morphine Equivalent Opioid Consumption (MEQ) | 1 year post surgery (last 24 hours) | 
| Physical functioning | Using interference component of mBPI-SF | 1 year post surgery | 
| 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 | 
| 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 | 
| The incidence of mortality at 1 year | Mortality at 1 year | 1 year post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anaesthesia, Local Anaesthesia, Chronic Post Surgical Pain