LOLIPOP trial

The LOLIPOP trial is a pragmatic, phase III, international, multicentre, double-blind, randomised trial that will compare the incidence of chronic post-surgical pain after breast cancer surgery in patients receiving a 24-hour infusion of lidocaine or placebo.

Progress

Recruitment for the LOLIPOP trial commenced in July 2022.  There are currently 41 sites actively participating, 19 sites in Australia, three sites in New Zealand, three sites in Hong Kong and 16 sites in the UK. We have further sites in Australia coming on board shortly. To date, 2222 patients have been recruited to the trial.

We would like to thank all of our sites and especially the LOLIPOP patients for their ongoing support of the trial.

Summary

Study summary

The LOLIPOP trial is a pragmatic, phase III, international, multicentre,  double-blind, randomised trial that will compare the incidence of chronic post-surgical pain after breast cancer surgery in patients receiving a 24-hour infusion of lidocaine or placebo.

Eligibility

Adult females undergoing unilateral or bilateral mastectomy or breast conserving surgery for a confirmed or suspected breast cancer diagnosis with no pre-existing pain at the operative site. Surgery involving immediate, autologous reconstruction is excluded.

Study intervention

Lidocaine infusion (or matched placebo) commencing with an intravenous bolus after induction of anaesthesia (2.5 mg per Kg lean body weight per hour), followed by an intravenous infusion for the duration of surgery (3.33 mg per Kg lean body weight per hour) and a subcutaneous infusion for up to 24 hours thereafter (2.22 mg per Kg lean body weight per hour).

Primary endpoint

Moderate or severe chronic post-surgical pain (CPSP) at 1 year after surgery as reported by the patient at follow-up  review.

Secondary endpoints

Chronic post-surgical pain of any severity; analgesic consumption; quality of life; surgical site infection; cancer recurrence.

Safety endpoints

Incidence of hypotension and bradycardia requiring treatment, incidence of infusion stopping events, incidence of suspected lidocaine toxicity events, incidence of suspected severe local anaesthetic toxicity events (generalised seizure, sudden unexplained loss of consciousness, life-threatening arrhythmia, cardiac arrest), and other adverse events.

Sample size

4300 patients.

Study duration

Six years.

Start-up meeting

The start-up meeting was held at the ANZCA CTN workshop on Saturday 7 August 2021. To get a copy of the recording, email Gillian Ormond.

Background

Women undergoing breast surgery and cancer treatment are a high-risk group for development of chronic postsurgical pain (CPSP), where it is estimated that nearly half of breast cancer surgery patients may develop  this outcome. A systematic review and meta-analysis by the study team observed a 71% reduction of the odds of CSPS (odds ratio [OR], 0.29; 95% CI, 0.18 to 0.48) with a number-needed-to-treat (NNT) of approximately 5 for lidocaine infusions - a finding that remained consistent in a planned sub-group analysis limited to breast surgery.  The primary purpose of a meta-analysis where there is insufficient evidence is in hypothesis generation and to identify equipoise. Hence, this very substantial reduction in the odds of CPSP must be tested in a properly conducted large trial. The team has published the results of the LOLIPOP pilot trial. This trial enrolled 150 patients and examined feasibility and safety outcomes in addition to pharmacokinetic data, in preparation for the large international multicentre trial.
In our recent survey of ANZCA Fellows, 52% of respondents reported the incorporation of perioperative lidocaine into their practice, with the principal aim to reduce acute surgical pain and opioid use. These findings, in addition to the results of the metaanalysis, confirm that there is equipoise regarding lidocaine as a perioperative intervention.  This trial will inform clinical practise globally.     

Funding

Australia

Medical Research Future Fund grant $A4.3 million (2021-2025).

The Australian National Health and Medical Research Council, Medical Research Future Fund Funding initiative: Rare Cancers, Rare Disease and Unmet Need Neurological Disorders 2020 grant $A4.3 million (2021-2025) National Institute for Health and Care Research UK. Funding Initiative: Health Technology Assessment (HTA) Programme grant £1.8 million GBP (2024-2028).

Hong Kong

Research Grants Council, Hong Kong, General Research Fund.

United Kingdom

National Institute for Health and Care Research UK. Funding Initiative: Health Technology Assessment (HTA) Programme grant £1.8 million GBP (2024-2028)

Operations committee

Prof Tomás Corcoran
A/Prof Andrew Toner
Ms Gillian Ormond
Ms Natalie Hird

Collaborators

Monash University, Melbourne
Royal Perth Hospital, Perth
Australian and New Zealand College of Anaesthetists Clinical Trials Network (ANZCA CTN)
University of Bristol (Bristol Trials Centre)
University Hospital Southampton NHS Foundation Trust, UK

Trial registration

ClinicalTrials.gov identifier: NCT05072314

Media releases

LOLIPOP trial receives $A3.8 million from UK’s National Institute for Health and Care Research 2 February 2024

Anaesthetists awarded key grant for pilot study into chronic pain after breast cancer surgery 22 December 2018

Participating hospitals

How to get involved

Please email complete this form if you are interested in taking part in the LOLIPOP trial.