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

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.

Study Overview

• Status: Recruiting
• Conditions: Pain, Postoperative; Breast Cancer; Pain, Chronic; Post-mastectomy Pain Syndrome
• Intervention / Treatment: Drug: Lidocaine 20mg/ml; Drug: Placebo

Detailed Description

PLAN is a multicentre, parallel-group, blinded, randomized controlled trial of 1,602 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

• Study Type: Interventional
• Enrollment (Estimated): 1602
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: James Khan; Phone Number: 3243 416-340-4800; Email: James.Khan@medportal.ca
• Study Contact Backup: Name: Nour Ayach; Phone Number: 4221 416-340-4800; Email: Nour.Ayach@uhn.ca

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • Recruiting
      • Foothills Medical Centre
      • Contact: May Lynn Quan, MD
    • Edmonton, Alberta, Canada
      • Recruiting
      • Sturgeon Community Hospital
      • Contact: Simone Derzi, MD
  • Newfoundland and Labrador
    • St. John's, Newfoundland and Labrador, Canada
      • Recruiting
      • Eastern Health- Health Sciences Centre
      • Contact: Geoff Zbitnew, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Recruiting
      • IWK
      • Contact: Allana Munro, MD
  • Ontario
    • Hamilton, Ontario, Canada
      • Recruiting
      • Juravinski Hospital
      • Contact: James Paul, MD
    • North York, Ontario, Canada
      • Recruiting
      • North York General Hospital
      • Contact: Brian Pinchuk, MD
    • Ottawa, Ontario, Canada
      • Recruiting
      • The Ottawa Hospital
      • Contact: Daniel McIsaac, MD
    • Thunder Bay, Ontario, Canada
      • Recruiting
      • Thunder Bay Regional Health Sciences Centre
      • Contact: Sudhakar Subramaniam Bharathidasan, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • Mount Sinai Hospital
      • Contact: James Khan, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Stephen Choi, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • University Health Network
      • Contact: Hance Clarke, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • St. Michael's Hospital
      • Contact: Karim Ladha, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • Humber River Hospital
      • Contact: Sinziana Avramescu, MD
    • Toronto, Ontario, Canada
      • Recruiting
      • Women's College Hospital
      • Contact: Richard Brull, MD
  • Quebec
    • Montreal, Quebec, Canada
      • Recruiting
      • Hôpital Maisonneuve-Rosemont
      • Contact: Philippe Richebe, MD
• Nepal
  • Dharān, Nepal
    • Recruiting
    • B.P. Koirala Institute of Health Sciences
• Nigeria
  • Ile-Ife, Nigeria
    • Recruiting
    • Obafemi Awolowo University Teaching Hospitals Complex
    • Contact: Funmilola Wuraola, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years old
2. 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:

1. Previous breast surgery within 6 months of index surgery
2. Undergoing any autologous flap procedure during index surgery
3. Presence known chronic pain disorder involving surgical site or ipsilateral chest wall, shoulder, or arm during the 3-months prior to index surgery
4. Documented hypersensitivity or allergy to lidocaine
5. 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)
6. History of ventricular tachycardia, ventricular fibrillation, or atrioventricular block without a pacemaker
7. Known cirrhotic liver disease
8. Pregnant
9. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Intraoperative intravenous lidocaine/placebo infusion	Drug: Lidocaine 20mg/ml; 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).; Other Names: Lidocaine 2%
Placebo Comparator: Control; Intraoperative intravenous lidocaine/placebo infusion	Drug: Placebo; 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).; Other Names: 0.9% sodium chloride solution

What is the study measuring?

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
Cost Effectiveness	Healthcare Costs associated with the burden of chronic post-surgical pain will be assessed	3 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: James Khan, MD, University Health Network, Toronto; Principal Investigator: PJ Devereaux, MD.PhD, Population Health Research Institute; Principal Investigator: Ian Gilron, MD, Kingston Health Sciences Centre

Publications and helpful links

General Publications

• Khan JS, Gilron I, Devereaux PJ, Clarke H, Ayach N, Tomlinson G, Quan ML, Ladha KS, Choi S, Munro A, Brull R, Lim DW, Avramescu S, Richebe P, Hodgson N, Paul J, McIsaac DI, Derzi S, Zbitnew GL, Easson AM, Siddiqui NT, Miles SJ, Karkouti K; PLAN Trial Investigators. Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial. Trials. 2024 May 22;25(1):337. doi: 10.1186/s13063-024-08151-4.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2021
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 30, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Estimated): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Pain, Postoperative; Chronic Pain; Breast Neoplasms; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Acetanilides; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Lidocaine; Sodium Chloride
• Other Study ID Numbers: 21-5021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No