Breast Cancer, Breast Cancer Female, Breast Conserving Surgery, Mastectomy
Conditions
Keywords
Anaesthesia, Local Anaesthesia, Chronic Post Surgical Pain
Brief summary
The LOLIPOP Trial is a large (n=4,300 patients) pragmatic, international, multicentre, prospective, randomised, double blind, placebo-controlled, parallel assessment, safety and effectiveness superiority study.
Detailed description
The Trial's purpose is to evaluate the effectiveness of lidocaine infusions commenced during surgery and extending up to 24 hours postoperatively, on the incidence of moderate or severe chronic post-surgical pain (CPSP) detected one year following surgery in female patients undergoing elective breast cancer surgery. The trial has 90% power to detect a clinically meaningful (25%) reduction in the incidence of the primary outcome. Secondary outcomes include safety events, analgesic efficacy (pain scores and opioid consumption), neuropathic characteristics of CPSP, and psychological and quality of life outcomes.
Interventions
DRUGlidocaine 2% and 10%
Lidocaine infusion: 1. Commencing with an intravenous bolus after induction of anaesthesia, 0.125 ml/kg of lean body weight (LBW) of 2% lidocaine (2.5 mg/kg).\* 2. Followed by a 2% lidocaine intravenous infusion for the duration of surgery, 0.1665 ml/kg/h of LBW (3.33 mg/kg/hr).\* 3. A post-operative subcutaneous 0.0222 ml/kg/hr of LBW 10% lidocaine infusion for up to 24 hours thereafter (2.22 mg/kg/hr). Dosage will be capped at a maximum lean body weight of 68kg. * \*Day-case surgery receives intraoperative bolus and intraoperative infusion only
DRUGPlacebo
Placebo infusion: 1. Commencing with an intravenous bolus after induction of anaesthesia, 0.125 ml/kg of lean body weight (LBW) of 0.9% Saline solution.\* 2. Followed by a 0.9% Saline solution intravenous infusion for the duration of surgery, 0.1665 ml/kg/h of LBW (3.33 mg/kg/hr).\* 3. A post-operative subcutaneous 0.0222 ml/kg/hr of LBW 0.9% Saline solution infusion for up to 24 hours thereafter (2.22 mg/kg/hr). Dosage will be capped at a maximum lean body weight of 68kg. * \*Day-case surgery receives intraoperative bolus and intraoperative infusion only
Sponsors
Monash University
Royal Perth Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
All trial participants, research coordinators, members of the anaesthesia and surgical teams, pharmacists, theatre and ward staff and all individuals performing patient follow up will be blinded to the patient's treatment allocation. All of the trial committees associated with the study will be blinded, with the exception of the Data Safety and Monitoring Committee (DSMC), who will receive unblinded (open) reports from the independent statistician. Unblinding of the patient's treatment allocation will be possible in exceptional circumstances, and a process will be in place to facilitate unblinding requests.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Consenting adult female patients (≥18 years) undergoing mastectomy (unilateral or bilateral) or breast conserving surgery (unilateral or bilateral) for the primary excision of confirmed or suspected primary breast cancer under general anaesthesia (including those with simultaneous insertion of tissue expanders or implants)\*. \* this specifically excludes patients undergoing surgery for locoregional recurrence * American Society of Anaesthesiologist (ASA) physical scale 1-3
Exclusion criteria
* Mastectomy or breast conserving surgery with add on procedures e.g laparoscopic salpingectomy * Where surgery is being performed for locoregional recurrence of breast cancer * Pre-existing pain at site of surgery, axilla, ipsilateral side of chest wall or the ipsilateral upper arm (at diagnosis prior to any tumor locating procedures) * Re-excision procedures where the margins at the index surgery have been deemed insufficient * When immediate autologous reconstruction surgery is planned * Where delayed autologous reconstruction surgery on the operative breast within one year is planned * Planned use of regional analgesia infusions * Impaired cognition * Pregnant or lactating females * Transgender patients * Known metastatic disease * History of anaphylaxis, sensitivity or known contraindication to lidocaine (or other amide local anaesthetic agents e.g. other amide local anaesthetic agents: ropivacaine, bupivacaine, mepivacaine, prilocaine, etidocaine), including patients with porphyria or methaemoglobinaemia * History of epilepsy * Baseline heart rate \< 50 bpm or systolic blood pressure \< 100mmHg. * Acute coronary event in the last three months * Cardiac conduction abnormalities, including; Atrial fibrillation, Heart block (all degrees), Bundle Branch Block or Fascicular block, Prolonged QT interval, Wolf Parkinson White syndrome, channelopathy such as Brugada syndrome. A preoperative Electrocardiogram (ECG) is not mandatory, unless clinically indicated * Abnormal serum potassium concentration (based upon site laboratory reference ranges) * Active liver disease e.g. viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, haemochromatosis, other rarer causes) * Medications within the last 7 days which are known / suspected to slow lidocaine metabolism (amiodarone, beta blockers, cimetidine, fluoroquinolones, fluvoxamine, imidazoles, macrolides, verapamil, HIV drugs) * Cardiac Failure (any documented heart failure at peroperative assessment or GP records) * Severe Renal Failure (Creatinine Clearance of less than 30ml/min or dialysis dependent) * Co-administration of lidocaine within 24 hours prior to surgery for other reasons (e.g. lidocaine patches
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of moderate or severe CPSP at 1 year after surgery, as reported by the patient at the follow-up review. | 1 year post-surgery | Numerical rating scale ≥4 out of 10 for worst pain in the last week - The pain must have been present for at least 3 months prior to the one year assessment (or longer). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of severe CPSP at 1 year after surgery | 1 year post surgery | NRS for worst pain the in the last week of ≥7) |
| Severity of pain at the site of surgery | 1 year post surgery | Assessed using "average" and "worst" NRS pain score in the last week, obtained from the adapted modified Brief Pain Inventory-Short Form (mBPI-SF) |
| Incidence of neuropathic symptoms | 1 year post surgery | Incidence examined as a binary outcome using the Short Form of Douleur Neuropathique 4 Questions (S-DN4) |
| Physical functioning | 1 year post surgery | Using interference component of mBPI-SF |
| Changes in quality of life metrics EuroQol 5 Dimension 5 Level (EQ-5D-5L) at 1 year after surgery compared to baseline | 1 year post surgery | Changes in the quality of life |
| Changes in psychological wellbeing Kessler Psychological Distress Scale (K-10) at 1 year after surgery compared to baseline. | 1 year post surgery | Changes in psychological wellbeing |
| The incidence of mild or greater pain at the site of surgery at 1 year after surgery | 1 year post surgery | NRS for worst pain the in the last week of ≥1 |
| The incidence of discomfort or altered sensation at the site of surgery (not reported as pain) | 1 year post surgery | Patients asked if they have any altered sensation at the site of surgery |
| Severity of acute postoperative pain at rest | 24 hours postoperatively | Maximum pain score, Numerical rating scale (NRS) 0-10 |
| Severity of Acute postoperative pain on movement | 24 hours postoperatively | Maximum pain score, Numerical rating scale (NRS) 0-10 |
| Postoperative opioid consumption | on Day 1 | Morphine Equivalent Opioid Consumption (MEQ) |
| The incidence of mortality at 1 year | 1 year post surgery | Mortality at 1 year |
| UK NHS costs of care over 1 year following surgery | 1 year post surgery | UK/NHS sites only |
| Productivity costs over 1 year following surgery | 1 year post surgery | UK/NHS sites only |
| Quality-adjusted life years (QALYs) over 1 year following surgery | 1 year post surgery | UK/NHS sites only |
| Cost-effectiveness of perioperative lidocaine infusions compared to usual care, from a primary UK NHS perspective and broader perspective including productivity, at 1 year. | 1 year post surgery | UK/NHS sites only |
Countries
Australia, Hong Kong, New Zealand, United Kingdom
Contacts
CONTACTGillian Ormond
CONTACTNatalie Hird
PRINCIPAL_INVESTIGATORTomas Corcoran
Royal Perth Hospital
Outcome results
None listed