Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial

Sponsor
Monash University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05072314
Collaborator
Royal Perth Hospital (Other)
4,300
Enrollment
2
Arms
72
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The LOLIPOP Trial is a large (n=4,300 patients) pragmatic, international, multicentre, prospective, randomised, double blind, placebo-controlled, parallel assessment, stratified safety and effectiveness superiority study.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: lidocaine 2% and 10%
  • Drug: Placebo
Phase 4

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. Patients will be stratified according to whether they undergo breast conserving surgery or mastectomy, and whether they have preoperative chronic pain at a site other than the surgical site. 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
4300 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, 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.
Primary Purpose:
Prevention
Official Title:
Long-term Outcomes of Lidocaine Infusions for Post-Operative Pain (LOLIPOP) Trial
Anticipated Study Start Date :
Feb 1, 2022
Anticipated Primary Completion Date :
Feb 1, 2027
Anticipated Study Completion Date :
Feb 1, 2028

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Lidocaine

2% Lidocaine infusion intra-operative and 10% Lidocaine infusion post-operative.

Drug: lidocaine 2% and 10%
Lidocaine infusion: Commencing with an intravenous bolus after induction of anaesthesia (2.5 mg/kg/hr), Followed by a 2% lidocaine intravenous infusion for the duration of surgery (3.33 mg/kg/hr) A post-operative subcutaneous 10% lidocaine infusion for up to 24 hours thereafter (2.22 mg/kg/hr).
Other Names:
  • Xylocaine (lidocaine) 2% and Xylocard (lidocaine) 10%
  • Placebo Comparator: Placebo

    0.9% Saline infusion intra-operative and 0.9% Saline infusion post-operative.

    Drug: Placebo
    Saline infusion: Commencing with an intravenous bolus after induction of anaesthesia (2.5 mg/kg/hr), Followed by a 2% lidocaine intravenous infusion for the duration of surgery (3.33 mg/kg/hr) A post-operative subcutaneous 10% lidocaine infusion for up to 24 hours thereafter (2.22 mg/kg/hr).
    Other Names:
  • 0.9% Saline solution
  • Outcome Measures

    Primary Outcome Measures

    1. The incidence of moderate or severe CPSP related to the site of surgery at 1 year after surgery [1 year post-surgery]

    Secondary Outcome Measures

    1. Severity of acute postoperative pain at rest [24 hours postoperatively]

      Maximum pain score, Numerical rating scale (NRS) 0-10

    2. Severity of Acute postoperative pain on movement [24 hours postoperatively]

      Maximum pain score, Numerical rating scale (NRS) 0-10

    3. Postoperative opioid consumption [24 hours postoperatively]

      Morphine Equivalent Opioid Consumption (MEQ)

    4. Postoperative opioid consumption [3 months (last 24-hours)]

      Morphine Equivalent Opioid Consumption (MEQ)

    5. The incidence of severe CPSP related to the site of surgery at 1 year after surgery [1 year post surgery]

      NRS for worst pain the in the last week of ≥7)

    6. The incidence of mild or greater CPSP related to the site of surgery at 1 year after surgery [1 year post surgery]

      NRS for worst pain the in the last week of ≥1

    7. The incidence of discomfort or altered sensation at the site of surgery (not reported as pain) [1 year post surgery]

    8. Severity of CPSP [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)

    9. Incidence of neuropathic symptoms [1 year post surgery]

      Incidence examined as a binary outcome using the Neuropathic Pain Questionnaire (NPQ)

    10. Postoperative opioid consumption [1 year post surgery (last 24 hours)]

      Morphine Equivalent Opioid Consumption (MEQ)

    11. Physical functioning [1 year post surgery]

      Using interference component of mBPI-SF

    12. 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]

    13. Changes in psychological wellbeing Kessler Psychological Distress Scale (K-10) at 1 year after surgery compared to baseline. [1 year post surgery]

    14. The incidence of mortality at 1 year [1 year post surgery]

    Other Outcome Measures

    1. Incidence of treated bradycardia [24 hours postoperatively]

      Drug related safety Endpoints

    2. Incidence of treated hypotension [24 hours postoperatively]

      Drug related safety Endpoints

    3. Incidence of treated arrhythmias [24 hours postoperatively]

      Drug related safety Endpoints

    4. Incidence of Medical Emergency Team (MET) activation [24 hours postoperatively]

      Drug related safety Endpoints

    5. Incidence of unplanned Intensive Care Unit (ICU), High Dependency Unit (HDU) or Critical Care Unit (CCU) admission [24 hours postoperatively]

      Drug related safety Endpoints

    6. Incidence of intraoperative infusion stopping events [24 hours postoperatively]

      Drug related safety Endpoints

    7. Incidence of Post Anaesthesia Care Unit (PACU) infusion stopping events [24 hours postoperatively]

      Drug related safety Endpoints, (x2 symptoms, x1 sign)

    8. Incidence of postoperative infusion stopping events [24 hours postoperatively]

      Drug related safety Endpoints, (x2 symptoms, x1 sign)

    9. Incidence of episodes of suspected severe local anaesthetic toxicity (LAST) [24 hours postoperatively]

      Drug related safety Endpoints,(generalised seizure, life-threatening arrhythmia, sudden unexplained loss of consciousness)

    10. Incidence of study drug unblinding events [24 hours postoperatively]

      Drug related safety Endpoints

    11. Incidence of subcutaneous catheter site events [24 hours postoperatively]

      Drug related safety Endpoints

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Consenting adult female patients (≥18 years, <80 years) undergoing mastectomy or breast conserving surgery for the primary excision of confirmed or suspected breast cancer under general anaesthesia (including those with simultaneous insertion of tissue expanders or implants).

    • American Society of Anaesthesiologist (ASA) physical scale 1-3

    Exclusion Criteria:
    • Pre-existing pain at site of surgery, axilla, ipsilateral side of chest wall or the ipsilateral upper arm

    • 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 or deemed likely

    • Planned use of regional analgesia infusions

    • Inability to communicate in English

    • Impaired cognition

    • Pregnant or lactating females

    • Known metastatic disease

    • 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; 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.

    • Abnormal serum potassium concentration (based upon site laboratory reference ranges)

    • Abnormal serum sodium 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)

    • Abnormal liver function tests (based upon site laboratory reference ranges)

    • 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

    • Severe Renal Failure (Creatinine Clearance of less than 30ml/min or dialysis dependent)

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Monash University
    • Royal Perth Hospital

    Investigators

    • Principal Investigator: Tomas Corcoran, Royal Perth Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Prof Tomas Corcoran, Chief Principal Investigator, Monash University
    ClinicalTrials.gov Identifier:
    NCT05072314
    Other Study ID Numbers:
    • HREC/74777/Alfred-2021
    First Posted:
    Oct 8, 2021
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Prof Tomas Corcoran, Chief Principal Investigator, Monash University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021