Perioperative Pregabalin and Lidocaine to Reduce Chronic Breast Cancer Pain

Study Overview
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Brief Summary
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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.

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

Conditions
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Post-mastectomy Pain Syndrome, Chronic Post-surgical Pain

Intervention / Treatment
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* Drug: Intraoperative Intravenous Lidocaine Infusion
* Drug: Perioperative Pregabalin
* Drug: Perioperative Pregabalin Placebo
* Drug: Intraoperative Intravenous Lidocaine Placebo Infusion


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pregabalin/Lidocaine<br>Perioperative Pregabalin, Intraoperative Intravenous Lidocaine Infusion | Drug: Intraoperative Intravenous Lidocaine Infusion<br>* 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.<br>* Other names: Xylocaine;Drug: Perioperative Pregabalin<br>* 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.<br>* Other names: Lyrica;|
| Active Comparator: Pregabalin Placebo/Lidocaine<br>Perioperative Pregabalin Placebo, Intraoperative Intravenous Lidocaine Infusion | Drug: Intraoperative Intravenous Lidocaine Infusion<br>* 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.<br>* Other names: Xylocaine;Drug: Perioperative Pregabalin Placebo<br>* 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.<br>|
| Active Comparator: Pregabalin/Lidocaine Placebo<br>Perioperative Pregabalin, Intraoperative Intravenous Lidocaine Placebo Infusion | Drug: Perioperative Pregabalin<br>* 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.<br>* Other names: Lyrica;Drug: Intraoperative Intravenous Lidocaine Placebo Infusion<br>* 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.<br>|
| Placebo Comparator: Pregabalin Placebo/Lidocaine Placebo<br>Perioperative Pregabalin Placebo, Intraoperative Intravenous Lidocaine Placebo Infusion | Drug: Perioperative Pregabalin Placebo<br>* 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.<br>Drug: Intraoperative Intravenous Lidocaine Placebo Infusion<br>* 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.<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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. | 
| Quality of Life |  | 3 months | 
| Somatic Pre-occupation and Coping Scale |  | 3 months | 
| Acute postoperative pain |  | Postoperative days 1-9 |