Lidocaine for Postoperative Pain in Breast Cancer

Recruiting at 18 trial locations

Overseen By Nour Ayach

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University Health Network, Toronto

Disqualifiers: Chronic pain, Lidocaine allergy, Pregnancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: During surgery

1602 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Phase III, international multicentre, parallel group, blinded, 1:1 randomized controlled trial to determine the effect of an intraoperative intravenous lidocaine infusion on reducing the development of persistent pain 3-months after breast cancer surgery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is lidocaine safe for use in humans, particularly for postoperative pain in breast cancer surgery?

Research shows that lidocaine is generally safe for use in humans, with rare in-hospital safety events reported in trials. Serum levels of lidocaine during treatment were within safe ranges, and no undesirable effects were observed in studies using lidocaine for pain management in breast cancer patients. ^{1 2 3 4 5}

How does the drug lidocaine differ from other treatments for postoperative pain in breast cancer surgery?

Lidocaine is unique because it is used as an intravenous infusion during and after breast cancer surgery to potentially prevent chronic postoperative pain, which is a common issue. This approach is different from standard pain management as it focuses on reducing long-term pain development rather than just addressing immediate postoperative pain. ^{2 4 5 6 7}

What data supports the effectiveness of the drug lidocaine for reducing postoperative pain in breast cancer surgery?

Research shows that using lidocaine during and after breast cancer surgery can reduce the chances of long-term pain. Studies found that patients receiving lidocaine had fewer pain issues compared to those who received a placebo, indicating its potential effectiveness in managing postoperative pain. ^{3 4 5 6 7}

Who Is on the Research Team?

James Khan, MD

Principal Investigator

University Health Network, Toronto

PJ Devereaux, MD.PhD

Principal Investigator

Population Health Research Institute

Ian Gilron, MD

Principal Investigator

Kingston Health Sciences Centre

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are having breast cancer surgery (lumpectomy or mastectomy) for any reason, including high risk without current cancer. It's not for those with recent breast surgery, chronic pain at the site, lidocaine allergy, certain heart conditions, liver disease, pregnancy or if they can't follow up.

Inclusion Criteria

I am having a lumpectomy or mastectomy, for any reason including prevention.

Exclusion Criteria

I had breast surgery less than 6 months ago.

I am having surgery using my own tissue for reconstruction.

I have had chronic pain in the area of my upcoming surgery or nearby areas in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an intraoperative intravenous lidocaine infusion or placebo during breast cancer surgery

During surgery

1 visit (in-person)

Immediate Postoperative Follow-up

Participants are monitored for pain, analgesic consumption, and recovery in the first 3 days after surgery

3 days

Daily follow-up (in-person or virtual)

Follow-up

Participants are monitored for persistent pain, functional outcomes, and quality of life at 3 and 12 months postoperatively

12 months

2 visits (in-person or virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Lidocaine 20mg/ml
• Placebo

Trial Overview The PLAN trial is testing whether giving an IV infusion of Lidocaine during breast cancer surgery can prevent long-term pain after the operation. Participants will be randomly assigned to receive either Lidocaine or a placebo in a blinded setup.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

Intraoperative intravenous lidocaine/placebo infusion

Group II: Control Placebo Group 1 Intervention

Intraoperative intravenous lidocaine/placebo infusion

Lidocaine 20mg/ml is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Xylocaine for:

• Prevention and control of pain in procedures involving the male and female urethra
• Topical treatment of painful urethritis
• Anesthetic lubricant for endotracheal intubation (oral and nasal)
• Production of local or regional anesthesia by infiltration techniques
• Percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques

Approved in European Union as Lidocaine for:

• Local anesthesia
• Regional anesthesia
• Pain relief in various medical procedures

Approved in Canada as Lidocaine for:

• Local anesthesia
• Regional anesthesia
• Pain relief in various medical procedures

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

A pilot study involving 150 patients undergoing breast cancer surgery demonstrated that peri-operative lidocaine infusion is safe, with in-hospital safety events occurring in only 3% of the lidocaine group compared to 1% in the placebo group.

The study showed that lidocaine levels during infusion were consistent with previous research, and while the adjusted odds ratio for postoperative pain at 6 months was 0.790, indicating a potential benefit, further large-scale trials are planned to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery. Toner, AJ., Bailey, MA., Schug, SA., et al.[2021]

In a study of 148 women undergoing breast cancer surgery, intravenous lidocaine significantly reduced the incidence of reported postsurgical pain at 6 months compared to saline, with 13% of lidocaine patients reporting pain versus 29% in the saline group (P = 0.04).

Despite the reduction in reported pain incidence, only a small number of patients in both groups met the criteria for persistent postoperative pain, indicating that while lidocaine may help with pain management, it does not fully prevent chronic pain outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Intraoperative Systemic Lidocaine on Postoperative Persistent Pain Using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials Criteria Assessment Following Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial. Kendall, MC., McCarthy, RJ., Panaro, S., et al.[2019]

Intravenous lidocaine significantly reduced the incidence of persistent postsurgical pain (PPSP) in breast cancer surgery patients, with only 11.8% experiencing PPSP compared to 47.4% in the control group after three months.

Lidocaine also decreased the severity of pain and secondary hyperalgesia, suggesting that it may prevent central hyperalgesia, which is a potential mechanism for its effectiveness in managing postoperative pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery. Grigoras, A., Lee, P., Sattar, F., et al.[2022]

Lidocaine 5% patches significantly improved pain severity in 20 patients with painful scars or chest wall tumors over a mean follow-up of 29.2 days, with 65% of patients reporting high satisfaction with the treatment.

The use of lidocaine patches did not lead to an increase in opioid dosage, and no significant side effects were reported, indicating a safe profile for short-term use in managing neuropathic cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lidocaine 5 % patches as an effective short-term co-analgesic in cancer pain. Preliminary results. Garzón-Rodríguez, C., Casals Merchan, M., Calsina-Berna, A., et al.[2021]

In a study of 82 female breast cancer patients, intravenous lidocaine infusion significantly reduced the incidence of chronic postoperative pain (CPSP) at 3 months (12.8% in the lidocaine group vs. 33.3% in the control group) and at 6 months (10.5% vs. 29.7%).

Lidocaine infusion also led to lower pain scores and reduced need for additional pain relief within the first 24 hours after surgery, indicating its effectiveness in managing both acute and chronic pain post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intravenous lidocaine on chronic postoperative pain in patients undergoing breast cancer surgery: a prospective, double-blind, randomized, placebo-controlled clinical trial. Xia, M., Wei, Q., Zhang, Q., et al.[2022]

In a retrospective study of 11 breast cancer patients with moderate-to-severe persistent postmastectomy pain (PPMP), treatment with 5% Lidocaine medicated plaster resulted in significant pain control within the first week.

The 5% Lidocaine medicated plaster was well-tolerated and can be considered a viable option for managing PPMP, especially given the limitations of current systemic drug treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of persistent postmastectomy pain with 5% Lidocaine medicated plaster]. Cruto, ME., Baricocchi, E., Battistella, M., et al.[2015]

Lidocaine hydrochloride jelly (Xylocaine jelly) effectively reduced dull pain in 5 women with skin metastases from breast cancer, allowing for decreased reliance on other analgesics like NSAIDs and opioids.

The application of XJ was safe, with blood levels of lidocaine remaining within the safe zone and no undesirable effects reported, making it a practical option for managing pain in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of lidocaine hydrochloride jelly for the treatment of pain caused by breast cancer metastases to the skin]. Waraya, M., Kosaka, Y., Sengoku, N., et al.[2013]

Citations

1. England pubmed.ncbi.nlm.nih.gov

A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

The Effect of Intraoperative Systemic Lidocaine on Postoperative Persistent Pain Using Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials Criteria Assessment Following Breast Cancer Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Perioperative intravenous lidocaine decreases the incidence of persistent pain after breast surgery. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Lidocaine 5 % patches as an effective short-term co-analgesic in cancer pain. Preliminary results. [2021]

5. China pubmed.ncbi.nlm.nih.gov

Effect of intravenous lidocaine on chronic postoperative pain in patients undergoing breast cancer surgery: a prospective, double-blind, randomized, placebo-controlled clinical trial. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

[Treatment of persistent postmastectomy pain with 5% Lidocaine medicated plaster]. [2015]

7. Japan pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of lidocaine hydrochloride jelly for the treatment of pain caused by breast cancer metastases to the skin]. [2013]