Perioperative Pregabalin and Lidocaine to Reduce Chronic Breast Cancer Pain (PLAN)

Pregabalin and Lidocaine in Breast Cancer Surgery to Alter Neuropathic Pain (PLAN): A Pilot Trial

Breast tissue and the areas surrounding the breast contain many small to medium-sized nerves. During surgery on the breast, these nerves can be inadvertently cut or damaged. Chemotherapy and radiotherapy after surgery worsen the injury experienced by these nerves. These nerves eventually become abnormal and provide pain signals to the brain well beyond the healing period after surgery. Patients with these abnormal nerves suffer from chronic pain in the breast area that persists for several years after surgery. Chronic pain is associated with a reduced quality of life, daily functioning, psychological distress, and contributes to excessive health care expenditures. There is encouraging data suggesting that an infusion of Lidocaine during surgery and Pregabalin given around the time of surgery can prevent the development of chronic pain after breast cancer surgery. A large randomized controlled trial is needed to determine the efficacy of these two interventions on reducing chronic pain after breast cancer surgery (e.g. within 3 months of surgery). A pilot trial is first needed to determine the feasibility of undertaking such a trial.

Study Overview

• Status: Completed
• Conditions: Post-mastectomy Pain Syndrome; Chronic Post-surgical Pain
• Intervention / Treatment: Drug: Intraoperative Intravenous Lidocaine Infusion; Drug: Perioperative Pregabalin; Drug: Perioperative Pregabalin Placebo; Drug: Intraoperative Intravenous Lidocaine Placebo Infusion

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Juravinski Hospital
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• female patients 18-75 years of age
• undergoing a unilateral or bilateral mastectomy or partial-mastectomy (breast conserving surgery), for prophylactic (e.g. family history or BRCA gene mutation) or belief of isolated (non-metastatic) cancerous lesions
• receiving a general anesthetic

Exclusion Criteria:

• previous breast surgery within six months of index surgery
• undergoing a DIEP (Deep Inferior Epigastric Perforator) flap procedure
• patient has chronic pain or a chronic pain syndrome for which they have taken 4 or more daily medications (i.e. opioids, anti-convulsants, anti-spasmodic, anti-depressants, anti-inflammatories) or routine pain intervention (i.e. nerve blocks) during the past 3 months
• documented hypersensitivity or allergy to pregabalin, gabapentin, or lidocaine
• history of ventricular tachycardia, ventricular fibrillation, or atrioventricular block ≥ type II
• history of congestive heart failure
• renal insufficiency with creatinine > 120 µmol/L
• known or previously documented cirrhosis
• pregnant
• unable to swallow study medications
• patient's surgeon believes patient is inappropriate for inclusion in trial
• unlikely to comply with follow-up (e.g. no fixed address, plans to move out of town)
• language difficulties that would impede valid completion of questionnaires
• patient requires gabapentin or pregabalin for a medical condition or has been taking gabapentin or pregabalin daily during the past 1 week

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pregabalin/Lidocaine; Perioperative Pregabalin, Intraoperative Intravenous Lidocaine Infusion	Drug: Intraoperative Intravenous Lidocaine Infusion; Lidocaine 1.5 mg/kg bolus with anesthesia induction followed by 2 mg/kg/hr infusion before the start of surgical incision and stopped at surgical closure.; Other Names: Xylocaine; Drug: Perioperative Pregabalin; Pregabalin 300 mg preoperatively (e.g. 2 hours prior to the start of surgery) and 75 mg twice a day for 9 days after surgery.; Other Names: Lyrica
Active Comparator: Pregabalin Placebo/Lidocaine; Perioperative Pregabalin Placebo, Intraoperative Intravenous Lidocaine Infusion	Drug: Intraoperative Intravenous Lidocaine Infusion; Lidocaine 1.5 mg/kg bolus with anesthesia induction followed by 2 mg/kg/hr infusion before the start of surgical incision and stopped at surgical closure.; Other Names: Xylocaine; Drug: Perioperative Pregabalin Placebo; Pregabalin placebo 300 mg preoperatively (e.g. 2 hours prior to the start of surgery) and 75 mg twice a day for 9 days after surgery.
Active Comparator: Pregabalin/Lidocaine Placebo; Perioperative Pregabalin, Intraoperative Intravenous Lidocaine Placebo Infusion	Drug: Perioperative Pregabalin; Pregabalin 300 mg preoperatively (e.g. 2 hours prior to the start of surgery) and 75 mg twice a day for 9 days after surgery.; Other Names: Lyrica; Drug: Intraoperative Intravenous Lidocaine Placebo Infusion; Lidocaine placebo 1.5 mg/kg bolus with anesthesia induction followed by 2 mg/kg/hr infusion before the start of surgical incision and stopped at surgical closure.
Placebo Comparator: Pregabalin Placebo/Lidocaine Placebo; Perioperative Pregabalin Placebo, Intraoperative Intravenous Lidocaine Placebo Infusion	Drug: Perioperative Pregabalin Placebo; Pregabalin placebo 300 mg preoperatively (e.g. 2 hours prior to the start of surgery) and 75 mg twice a day for 9 days after surgery.; Drug: Intraoperative Intravenous Lidocaine Placebo Infusion; Lidocaine placebo 1.5 mg/kg bolus with anesthesia induction followed by 2 mg/kg/hr infusion before the start of surgical incision and stopped at surgical closure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility	The feasibility outcome will be measured by the rate of recruitment, compliance, percentage of patient's with complete follow-up and site resource requirements.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life		3 months
Post-mastectomy pain syndrome		6 months
Length of hospital stay	Most breast cancer surgeries are day procedures, therefore length of hospital stay will be measured based on whether or not the patient was discharged from the hospital on the same day as surgery or if they were admitted and remained in hospital overnight.	Total number of overnight stays spent in hospital continuously from the day of surgery until a maximum of 3 months post-operatively.
Somatic Pre-occupation and Coping Scale		3 months
Acute postoperative pain		Postoperative days 1-9

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Hamilton Health Sciences Corporation
• Investigators: Study Director: James S Khan, BHSc, MD, Population Health Research Institute

Publications and helpful links

General Publications

• Khan JS, Hodgson N, Choi S, Reid S, Paul JE, Hong NJL, Holloway C, Busse JW, Gilron I, Buckley DN, McGillion M, Clarke H, Katz J, Mackey S, Avram R, Pohl K, Rao-Melacini P, Devereaux PJ. Perioperative Pregabalin and Intraoperative Lidocaine Infusion to Reduce Persistent Neuropathic Pain After Breast Cancer Surgery: A Multicenter, Factorial, Randomized, Controlled Pilot Trial. J Pain. 2019 Aug;20(8):980-993. doi: 10.1016/j.jpain.2019.02.010. Epub 2019 Mar 5.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: August 19, 2014
• First Submitted That Met QC Criteria: September 11, 2014
• First Posted (Estimate): September 15, 2014

Study Record Updates

• Last Update Posted (Actual): April 24, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Lidocaine; Pregabalin
• Other Study ID Numbers: PLAN14001

Plan for Individual participant data (IPD)

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