Prevention of Persistent Pain With LidocAine iNfusions in Breast Cancer Surgery (PLAN)

Study Overview
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Brief Summary
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Phase III, international multicentre, parallel group, blinded, 1:1 randomized controlled trial to determine the effect of an intraoperative intravenous lidocaine infusion on reducing the development of persistent pain 3-months after breast cancer surgery.

Detailed Description
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PLAN is a multicentre, parallel-group, blinded, randomized controlled trial of 1,150 patients undergoing breast cancer surgery. Consented eligible patients will be randomized to receive an intravenous lidocaine: 1.5 mg/kg bolus with induction of general anesthesia followed by a 2.0 mg/kg/hour infusion until the end of surgery (and up to 30 minutes into recovery room). Patients in the control group will receive a placebo bolus and infusion with normal saline (0.9% sodium chloride solution). Study medications will be prepared in blinded 50 mL syringes and labelled as per Regulatory requirements. Patients will follow up on the first 3 days after surgery, and at 3 and 12-months postoperatively to report on pain, analgesic consumption, functional, mood, and quality of life outcomes

Official Title
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Prevention of Persistent Pain With LidocAine iNfusions in Breast Cancer Surgery (PLAN)

Conditions
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Post-mastectomy Pain Syndrome, Breast Cancer, Pain, Postoperative, Pain, Chronic

Intervention / Treatment
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* Drug: Lidocaine 20mg/ml
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old Undergoing a unilateral or bilateral lumpectomy or mastectomy, inclusive of all pathologies, including prophylactic surgery (e.g., family history or BRCA gene mutation) Exclusion Criteria: Previous breast surgery within 6 months of index surgery Undergoing any autologous flap procedure during index surgery Presence known chronic pain disorder involving surgical site or ipsilateral chest wall, shoulder, or arm during the 3-months prior to index surgery Documented hypersensitivity or allergy to lidocaine Surgery not planned to be performed under general anesthesia and/or planned use of regional or neuraxial anesthetic techniques before surgery (i.e., epidural, paravertebral, serratus plane block, pectoralis or modified pectoralis block) History of ventricular tachycardia, ventricular fibrillation, or atrioventricular block without a pacemaker Known cirrhotic liver disease Pregnant Unlikely to comply with follow-up (e.g. no fixed address, language difficulties that would impede valid completion of questionnaires, plans to move out of town)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

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 |
| --- | --- |
| Experimental: Intervention<br>Intraoperative intravenous lidocaine/placebo infusion | Drug: Lidocaine 20mg/ml<br>* Patients in the intervention group will receive an IV lidocaine infusion using a dosage regimen of 1.5 mg/kg bolus of a 2% lidocaine solution with induction of general anesthesia followed by a 2.0 mg/kg/hour infusion until the end of surgery (and up to 30 minutes into recovery room).<br>* Other names: Lidocaine 2%;|
| Placebo Comparator: Control<br>Intraoperative intravenous lidocaine/placebo infusion | Drug: Placebo<br>* Patients in the control group will receive a placebo bolus and infusion with normal saline (0.9% sodium chloride solution) until the end of surgery (and up to 30 minutes into recovery room).<br>* Other names: 0.9% sodium chloride solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of persistent pain 3-months after breast cancer surgery | Persistent pain at 3-months | 3- months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensities | Pain intensities measured on the Numeric Rating Scale (NSR) at rest and movement. | 3 and 12 months | 
| Opioid consumption | Morphine-equivalent opioid consumption | 3 and 12 months | 
| Moderate-to-severe persistent pain | Defined as persistent pain with an NRS pain score of ≥4 at rest 24-hours | 3 and 12 months | 
| Persistent neuropathic pain | Measured using the Douleur Neuropathique 4-symptoms interview | 3 and 12 months | 
| Sensory and affective qualities of pain | Quality of pain is reported using the Short Form McGill Pain Questionnaire | 3 and 12 months | 
| Emotional functioning | Emotional functioning is reported using the Profile of Mood States (POMS) | 3 and 12 months | 
| Physical functioning | Physical functioning measured by the interference scale of the Brief Pain Inventory-Short Form. | 3 and 12 months | 
| Health-related quality of life quality of life | Health-related quality of life will be assessed using EQ-5D-5L | 3 and 12 months | 
| Cancer Recurrence | Cancer recurrence will be assessed as a secondary outcome | 3 and 12 months | 
| Adverse events | Adverse Events will be monitored as a secondary safety outcome | 3 and 12 months |