Lidocaine for Postoperative Pain in Breast Cancer

Recruiting at 20 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?

This trial explores whether lidocaine, a common numbing medication, can reduce long-term pain after breast cancer surgery. Participants will receive either lidocaine or a placebo (a harmless substance resembling the treatment) during their operation. Researchers aim to determine if lidocaine affects pain levels three months post-surgery. Ideal candidates for this trial are those planning to undergo a lumpectomy or mastectomy and have not had breast surgery in the past six months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using intravenous lidocaine during surgery is generally safe. In one study, patients who received lidocaine experienced less long-term pain after breast cancer surgery compared to those who received a placebo. Another review involving 97 patients found that lidocaine significantly reduced pain 3 to 6 months after surgery.

Most studies have not reported serious side effects from lidocaine. However, like any medication, it may cause mild side effects such as dizziness or numbness. These effects are usually temporary and resolve on their own. Since this trial is in an advanced stage, lidocaine has already been tested in many people and found to be safe enough for further study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for postoperative pain in breast cancer?

Unlike traditional treatments for postoperative pain in breast cancer, which often rely on opioids or non-steroidal anti-inflammatory drugs (NSAIDs), this study explores the use of lidocaine, a local anesthetic, administered intravenously during surgery. Lidocaine is unique because it can directly block pain signals at their source, potentially reducing the need for opioids and their associated side effects. Researchers are excited about this approach because it might offer quicker pain relief with fewer complications, making recovery smoother and more comfortable for patients.

What evidence suggests that lidocaine might be an effective treatment for postoperative pain in breast cancer?

Research has shown that intravenous lidocaine, which participants in this trial may receive, can help reduce long-lasting pain after breast cancer surgery. One study found it lowered the chance of chronic pain three to six months post-surgery. Reviews of multiple studies also indicate that lidocaine can lessen pain and reduce the need for opioids after surgery. However, some studies suggest lidocaine might not aid in long-term pain relief after breast cancer surgery. Overall, evidence suggests lidocaine may help with postoperative pain, but results can vary. Participants in this trial will receive either lidocaine or a placebo to evaluate its effectiveness in managing postoperative pain. ^{1 2 3 4 6}

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

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]

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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9372649/

Effect of intravenous lidocaine on chronic postoperative pain ... Intravenous infusion of lidocaine reduces the incidence of CPSP in breast cancer patients at 3 and 6 months and is effective in relieving acute postoperative ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10327428/

Perioperative intravenous lidocaine for postoperative pain in ... Previous meta-analyses have demonstrated the effectiveness of intravenous lidocaine in reducing postoperative pain and opioid consumption in ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0007091223006980

Pain The analgesic effectiveness of perioperative lidocaine ... Our results provide moderate-quality evidence that perioperative lidocaine infusion does not reduce CPSP in patients undergoing breast cancer surgery.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05072314

Long-term Outcomes of Lidocaine Infusions for Post- ... The trial's purpose is to evaluate the effectiveness of lidocaine infusions commenced during surgery and extending up to 24 hours postoperatively.

5. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-024-08151-4

Prevention of persistent pain with lidocaine infusions in breast ... In a systematic review (97 patients), intraoperative lidocaine compared to placebo significantly reduced persistent pain 3 to 6 months after ...

6. rapm.bmj.com rapm.bmj.com/content/39/6/472.full

Effect of Intravenous Lidocaine on Postoperative Recovery ... Conclusions Our findings did not show a significant effect of IV lidocaine during breast cancer surgery on opioid consumption, pain score, PONV, or fatigue, ...