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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат lidocaine 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 recei
• Препарат Placebo
  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 surg

Первичные конечные точки

• The incidence of moderate or severe CPSP at 1 year after surgery, as reported by the patient at the follow-up review. [Срок оценки: 1 year post-surgery]

Вторичные конечные точки (12)

• The incidence of severe CPSP at 1 year after surgery [Срок оценки: 1 year post surgery]
• Severity of pain at the site of surgery [Срок оценки: 1 year post surgery]
• Incidence of neuropathic symptoms [Срок оценки: 1 year post surgery]
• Physical functioning [Срок оценки: 1 year post surgery]
• Changes in quality of life metrics EuroQol 5 Dimension 5 Level (EQ-5D-5L) at 1 year after surgery compared to baseline [Срок оценки: 1 year post surgery]
• Changes in psychological wellbeing Kessler Psychological Distress Scale (K-10) at 1 year after surgery compared to baseline. [Срок оценки: 1 year post surgery]
• The incidence of mild or greater pain at the site of surgery at 1 year after surgery [Срок оценки: 1 year post surgery]
• The incidence of discomfort or altered sensation at the site of surgery (not reported as pain) [Срок оценки: 1 year post surgery]
• Severity of acute postoperative pain at rest [Срок оценки: 24 hours postoperatively]
• Severity of Acute postoperative pain on movement [Срок оценки: 24 hours postoperatively]
• Postoperative opioid consumption [Срок оценки: on Day 1]
• Postoperative opioid consumption [Срок оценки: 3 months (last 24-hours)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Профилактика

Центры проведения

Австралия · 26 центров

• Nepean Hospital — Kingswood
• Blacktown Mount Druitt Hospital — Mount Druitt
• Royal North Shore Hospital — Sydney
• Westmead Hospital — Sydney
• St George Hospital — Sydney
• Royal Brisbane and Women's Hospital — Brisbane
• Queen Elizabeth II Jubilee Hospital — Coopers Plains
• Mackay Base Hospital — Mackay
• … и ещё 18 центров

Великобритания · 15 центров

• University Hospital Wishaw — Wishaw
• Belfast City Hospital — Belfast
• Southmead Hospital, North Bristol Trust — Bristol
• Darlington Memorial Hospital — Darlington
• Russells Hall Hospital — Dudley
• Royal Liverpool and Broadgreen Hospitals — Liverpool
• Whittington Hospital — London
• Royal Marsden Hospital - London and Sutton — London
• … и ещё 7 центров

Гонконг · 3 центра

• North District Hospital — Shatin
• Pamela Youde Nethersole Eastern Hospital — Chai Wan
• Ruttonjee Hospital — Wan Chai

Новая Зеландия · 3 центра

• Auckland City Hospital — Auckland
• Middlemore Hospital — Auckland
• Waikato Hospital — Hamilton

Публикации

• Toner AJ, Bailey MA, Schug SA, Corcoran TB. A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery. Anaesthesia. 2021 Oct;76(10):1326-1341. doi: 10.1111/anae.15440. Epub 2021 Mar 2. PMID 33651896
• Toner AJ, Bailey MA, Schug SA, Phillips M, Ungerer JP, Somogyi AA, Corcoran TB. Serum lidocaine (lignocaine) concentrations during prolonged perioperative infusion in patients undergoing breast cancer surgery: A secondary analysis of a randomised controlled trial. Anaesth Intensive Care. 2023 Nov;51(6):422-431. doi: 10.1177/0310057X231194833. Epub 2023 Oct 6. PMID 37802488

Идентификаторы

NCT: NCT05072314 · HREC/74777/Alfred-2021

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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