Perioperative Pregabalin and Lidocaine to Reduce Chronic Breast Cancer Pain

NCT ID: NCT02240199

Last Updated: 2018-04-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2016-01-31

Brief Summary

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.

Conditions

Post-mastectomy Pain Syndrome; Chronic Post-surgical Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Pregabalin/Lidocaine

Perioperative Pregabalin, Intraoperative Intravenous Lidocaine Infusion

Group Type: EXPERIMENTAL

Intraoperative Intravenous Lidocaine Infusion

Intervention Type: DRUG

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.

Perioperative Pregabalin

Intervention Type: DRUG

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.

Pregabalin Placebo/Lidocaine

Perioperative Pregabalin Placebo, Intraoperative Intravenous Lidocaine Infusion

Group Type: ACTIVE_COMPARATOR

Intraoperative Intravenous Lidocaine Infusion

Intervention Type: DRUG

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.

Perioperative Pregabalin Placebo

Intervention Type: DRUG

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.

Pregabalin/Lidocaine Placebo

Perioperative Pregabalin, Intraoperative Intravenous Lidocaine Placebo Infusion

Group Type: ACTIVE_COMPARATOR

Perioperative Pregabalin

Intervention Type: DRUG

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.

Intraoperative Intravenous Lidocaine Placebo Infusion

Intervention Type: DRUG

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.

Pregabalin Placebo/Lidocaine Placebo

Perioperative Pregabalin Placebo, Intraoperative Intravenous Lidocaine Placebo Infusion

Group Type: PLACEBO_COMPARATOR

Perioperative Pregabalin Placebo

Intervention Type: DRUG

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.

Intraoperative Intravenous Lidocaine Placebo Infusion

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Xylocaine; Lyrica

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: collaborator

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James S Khan, BHSc, MD

Role: STUDY_DIRECTOR

Population Health Research Institute

P.J. Devereaux, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Population Health Research Institute

Locations

Juravinski Hospital

Hamilton, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 30844507 (View on PubMed)

Other Identifiers

PLAN14001

Identifier Type: -

Identifier Source: org_study_id