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Trial registered on ANZCTR


Registration number
ACTRN12618000463279
Ethics application status
Approved
Date submitted
13/03/2018
Date registered
29/03/2018
Date last updated
6/09/2019
Date data sharing statement initially provided
5/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Does an infusion of lidocaine, around the time of breast surgery, reduce the chance of ongoing pain in the site of surgery after 6 months?
Scientific title
Long-term Outcomes after Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Pilot Study: Do intravenous and subcutaneous lidocaine infusions provide an effective and feasible method of reducing persistent pain 6 months after breast cancer surgery?
Secondary ID [1] 294050 0
Nil known
Universal Trial Number (UTN)
U1111-1209-3705
Trial acronym
LOLIPOP
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 306599 0
Chronic Pain 306600 0
Condition category
Condition code
Anaesthesiology 305694 305694 0 0
Pain management
Cancer 306226 306226 0 0
Breast
Surgery 306227 306227 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
At the time of induction, prior to surgical incision, a bolus of 1.5mg/kg of Lidocaine will be delivered intravenously followed by 2mg/kg/hr for the duration of surgery by the treating anaesthetist. This will be under research coordinator supervision with appropriate dosing checked by both the clinical and the research team. At the end of the case the total dose will be recorded along with the duration of the case. In the post anaesthesia care unit, a subcutaneous infusion of 1.33mg/kg/hr will be commenced for a duration of 12 hours. There will be four hourly saftety checks by ward staff and a research coordinator review on the ward. The research staff will be available 24/7 in the event of uncertainties.
Intervention code [1] 300324 0
Prevention
Intervention code [2] 300325 0
Treatment: Drugs
Comparator / control treatment
The regime will be identical to the active regime but instead of lidocaine, an identical volume of normal saline will be used.
Control group
Placebo

Outcomes
Primary outcome [1] 304783 0
The feasibility of the trial process as described. Both to determine the rate at which we can recruit over the three sites. Also to determine whether we can meet an expected target of over 90% of subjects followed up at 6 months and appropriately surveyed as per secondary endpoints. This will be a composite endpoint of number recruited and followed up over a one year period (with 6 extra months for follow up). This outcome will be assessed qualitatively and quantitatively (an absolute count and descriptive statistics of missing datapoints in the Case Report Form). This information will be assessed by looking at the study records and the adverse event documentation (which will be compiled from hospital records should they occur).
Timepoint [1] 304783 0
At 6 months post surgery.
Primary outcome [2] 304784 0
Effectiveness of the Lidocaine regime as described in maintaining a clinically relevant concentration in the plasma. This will be measured at specific timepoints. A level less than 1.5 mcg/ml is unlikely to be effective whereas a level greater than 2mcg/ml is shown to be a good target level in previous work.
Timepoint [2] 304784 0
Plasma levels taken 30 minutes into the Post Anaesthesia Care Unit and at 6 hours post commencement of the subcutaneous infusion (The primary timepoint). These will be taken by a member of the research team.
Primary outcome [3] 305245 0
Safety of the intervention as described. Specifically this will include a qualitative assessment of any adverse events or possible local anaesthetic toxicity (and a quantitative assessment if possible). Serious adverse events may include arrhythmias, seizures, cardiovascular collapse, medical emergency team activation, DVT, Cerebrovascular accidents, Pulmonary Embolism and unexpected reoperation. These will be collected as composite safety outcomes.
Timepoint [3] 305245 0
At hospital discharge.
Secondary outcome [1] 343172 0
Highest pain score in Post Anaesthesia Care Unit (PACU) recorded by the clinical nurse caring for the patient and collated by the research staff. This will be a numerical rating scale (0-10).
Timepoint [1] 343172 0
On discharge from the PACU
Secondary outcome [2] 343173 0
This information will be asked at 24 hours and at 48 hours if still in hospital.
Timepoint [2] 343173 0
On discharge from hospital.
Secondary outcome [3] 343174 0
The pain score will be asked at 24 hours and at 48 hours if they are still in hospital.
Timepoint [3] 343174 0
On discharge from hospital.
Secondary outcome [4] 343175 0
Modified brief pain inventory. A validated exploration of pain severity and impact.
Timepoint [4] 343175 0
At 3 and 6 months post surgery.
Secondary outcome [5] 343176 0
Neuropathic Pain Questionnaire. A validated questionnaire determining whether the pain has a neuropathic component.
Timepoint [5] 343176 0
At 3 and 6 months post surgery.
Secondary outcome [6] 343177 0
Patient Catastrophizing scale. Looking at the psychological responses that people have towards their pain. A validated questionnaire for susceptibility for postoperative pain.
Timepoint [6] 343177 0
At 24 hours post end of surgery and at 3 and 6 months post surgery
Secondary outcome [7] 343178 0
World Health Organisation Disability Assessment Scale - WHODAS 2.0. which covers 6 domains of functioning which may feasibly be altered by anaesthetic technique (Cognition, mobility, self-care, getting along, life activities and participation). It has been extensively validated. These questions will be asked by research staff.
Timepoint [7] 343178 0
At baseline and at 3 and 6 months post surgery.
Secondary outcome [8] 343179 0
Intraoperative Opioid dose measured in morphine equivalents and taken directly from the medication administration documentation.
Timepoint [8] 343179 0
At end of surgery
Secondary outcome [9] 343180 0
Opioid dose in PACU measured in morphine equivalents and taken directly from the medication administration documentation.
Timepoint [9] 343180 0
End of PACU stay
Secondary outcome [10] 343181 0
Opioid dosing on ward measured in morphine equivalents and taken directly from the medication administration documentation.
Timepoint [10] 343181 0
24 hours post surgery.
Secondary outcome [11] 343182 0
Use of opioids in the past week measured in oral morphine equivalent doses.
Timepoint [11] 343182 0
3 and 6 months post surgery
Secondary outcome [12] 343184 0
Ropivacaine levels (A serum assay of the total ropivacaine concentration) to assess the toxicity potential of surgeon delivered local anaesthetic toxicity. This will be used to explore the additive effects of local anaesthetic agents should toxicity symptoms occur.
Timepoint [12] 343184 0
PACU at 30 minutes and at 6 hours post operatively.
Secondary outcome [13] 343186 0
Days out of hospital at 30 days (A composite of duration of hospital stay and further admissions subtracted from 30 days). This information will be gained from the hospital administrative data and confirmed against the patient's history.
Timepoint [13] 343186 0
30 days post surgery
Secondary outcome [14] 343187 0
Incidence of wound infection at 30 days. This is on direct questioning of the patient, clinic records and hospital admission notes. GP notes will be requested if patient reports possible infection.
Timepoint [14] 343187 0
30 days post surgery
Secondary outcome [15] 343188 0
Minor Local Anaesthetic Toxicity symptoms measured at four hourly intervals from PACU until 12 hours post commencing the subcutaneous infusion. These will be from a specific questionnaire asking whether the subject has experienced tinnitus, visual disturbance, dizziness, perioral numbness or metallic taste. This questionnaire has been designed for the purpose of this study as there are no validated options available. It does reflect the well documented side effects in a number of previous dose determining trials.
Timepoint [15] 343188 0
Collated at discharge
Secondary outcome [16] 343189 0
Quality of Recovery 15 point score assessing an overall measure of recovery across a number of domains (pain, nausea, mood). Asked by research assistant staff. This has been validated.
Timepoint [16] 343189 0
24 hours post surgery
Secondary outcome [17] 344617 0
The prevalence of Chronic Post Surgical Pain (CPSP) at 6 months defined as any pain (as a binary measure) at the surgical site that cannot be explained by other causes, such as disease recurrence or pre-existing pain. This will be identified during a phone interview.
Timepoint [17] 344617 0
We will ask for presence of pain at 3 months and 6 months.
Secondary outcome [18] 367813 0
Nausea - A numerical rating scale out of ten.
Timepoint [18] 367813 0
In PACU and on day 1

Eligibility
Key inclusion criteria
Adult females whom have a American Society of Anesthesiologists physical scale of 1 to 3 and are undergoing breast cancer surgery excluding hookwire guided excisions.
Minimum age
18 Years
Maximum age
80 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Use of flap from distant site (e.g. DIEP, TRAM, Latissmus Dorsi); Surgery which is being repeated or where the margins have been deemed insufficient; Breast Reduction Surgery; When further surgery within 30 days is planned or likely; Known Metastatic Disease; Pregnant and Lactating Women; Non-English speaking or other obvious difficulty with communication; No access to telephone; Cognitive deficit or obvious cognitive decline; Severe Renal Failure (Creatinine Clearance of less than 30ml/min or dialysis dependent); Hepatic derangement or documented liver disease; Heart failure; Epilepsy; sensitivity to Lidocaine or other amide local anaesthetic; Unstable Ischaemic heart disease; Atrial Fibrillation; Heart block (all degrees); Complete Bundle Branch Block, Fasicular block; Prolonged QT interval; Wolf Parkinson White syndrome; Syncope; Baseline hypotension (Systolic BP < 90mmHg); Antipsychotic medications; Antiretroviral therapies; Potent 1A2 inhibitors (Ciprofloxacin or Norfloxacin); 3A4 inhibitors (Itraconazole or Ketoconazole); Abnormal Serum Potassium (<3.5 or >5mmol/L); Baseline resting oxygen saturations below 94%.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The individual syringes will be coded and the patient will be assigned to a specific syringe via a computerised randomisation. An unblinding opaque envelope will be provided with instructions on the content of the syringe should a life threatening complication occur.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Primary Outcomes
Recruitment rates and follow up rates will be presented as raw data. The lidocaine levels will be presented using descriptive statistics. The safety outcomes will be compared using a chi squared test if appropriate.

Secondary Outcome
The absolute difference in Chronic Pain rates will be summarised with a two-sided 95% confidence interval. Adjustment for stratification variables and other baseline covariates if necessary will be performed using binomial identity regression to estimate the adjusted absolute difference in rates of chronic pain directly with its 95% CI.
Other outcomes and subgroups
Binary secondary outcomes will be analysed similar to the primary outcome. For continuous secondary outcomes, a linear regression model will be fitted with a model specification similar to that used for the primary outcome. Adverse events will be summarised.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 10020 0
Royal Perth Hospital - Perth
Recruitment hospital [2] 10021 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [3] 10022 0
St John of God Hospital, Subiaco - Subiaco
Recruitment postcode(s) [1] 19346 0
6000 - Perth
Recruitment postcode(s) [2] 19347 0
6150 - Murdoch
Recruitment postcode(s) [3] 19348 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 298675 0
Hospital
Name [1] 298675 0
Royal Perth Hospital
Address [1] 298675 0
197 Wellington Street, Perth, WA, 6000
Country [1] 298675 0
Australia
Funding source category [2] 303750 0
Charities/Societies/Foundations
Name [2] 303750 0
Australia and New Zealand College of Anaesthetists
Address [2] 303750 0
ANZCA House,
630 St Kilda Road,
Melbourne, Victoria 3004,
Australia.
Country [2] 303750 0
Australia
Funding source category [3] 303751 0
Charities/Societies/Foundations
Name [3] 303751 0
Royal Perth Hospital Medical Research Foundation
Address [3] 303751 0
Royal Perth Hospital Medical Research Foundation Incorporated
PO Box 2323, East Perth WA 6892
Country [3] 303751 0
Australia
Primary sponsor type
Hospital
Name
Royal Perth Hospital
Address
Royal Perth Hospital, Wellington Street, Perth, WA 6000, Australia
Country
Australia
Secondary sponsor category [1] 298197 0
None
Name [1] 298197 0
Address [1] 298197 0
Country [1] 298197 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299629 0
South Metropolitan Health Service
Ethics committee address [1] 299629 0
11 Robin Warren Drive, Murdoch, Western Australia, Australia, 6150.
Ethics committee country [1] 299629 0
Australia
Date submitted for ethics approval [1] 299629 0
12/11/2017
Approval date [1] 299629 0
22/12/2017
Ethics approval number [1] 299629 0
RGS0000000554

Summary
Brief summary
The purpose of this study is to determine whether a study to look at the safety and efficacy of an infusion of lidocaine at the time of breast surgery is feasible.

Who is it for?

You may be eligible for this study if you are over the age of 18 and are undergoing breast cancer surgery.

Study details

Participants will be randomised to one of two groups. One group will be given a lidocaine infusion during and for 12 hours after breast cancer surgery, and the other group will be given a placebo infusion.

Participants will then undergo a number of tests including lidocaine levels in the blood at two different time points after your surgery and inflammatory proteins to see if these are altered by the infusion. They will also be followed up by researchers for 6 months following the breast cancer surgery.

It is hoped that this research will help expand research in long-term pain relief for those undergoing breast cancer surgeries.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 81094 0
Prof Tomas Corcoran
Address 81094 0
Royal Perth Hospital, 197 Wellington Street, Perth, WA, 6000
Country 81094 0
Australia
Phone 81094 0
+61892242244
Fax 81094 0
Email 81094 0
tomas.corcoran@health.wa.gov.au
Contact person for public queries
Name 81095 0
Dr Martin Bailey
Address 81095 0
Royal Perth Hospital, 197 Wellington Street, Perth, WA, 6000
Country 81095 0
Australia
Phone 81095 0
+61892242244
Fax 81095 0
Email 81095 0
martinbaileynz@gmail.com
Contact person for scientific queries
Name 81096 0
Dr Martin Bailey
Address 81096 0
Royal Perth Hospital, 197 Wellington Street, Perth, WA, 6000
Country 81096 0
Australia
Phone 81096 0
+61892242244
Fax 81096 0
Email 81096 0
martinbaileynz@gmail.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Our clinical trial network has made a decision not to make trial data available.
What supporting documents are/will be available?
No other documents available
Summary results
No Results