Ketamine for Post Mastectomy Pain

Overseen By Kristin L Schreiber, MD/PhD

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: Brigham and Women's Hospital

Disqualifiers: Pregnant, Schizophrenia, Bipolar, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether ketamine, administered during surgery, can reduce pain after a mastectomy (breast removal surgery). The researchers aim to determine if ketamine can decrease both immediate and long-term pain and lessen the need for painkillers like opioids. Women scheduled for a total or partial mastectomy and willing to receive either ketamine or a placebo during surgery may be suitable for this study. The trial includes women at high risk of persistent pain after surgery to assess if ketamine is particularly beneficial for them. As an Early Phase 1 trial, this research focuses on understanding ketamine's effects in people, offering participants the chance to contribute to groundbreaking insights into pain management.

Do I need to stop my current medications for the trial?

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 shows that ketamine can help manage pain during surgery. In some studies, people who received ketamine during surgery reported less pain afterward. For example, one study found that ketamine controlled both immediate and long-term pain post-surgery. Another study suggested that ketamine might be more effective when administered intravenously rather than subcutaneously.

Regarding safety, ketamine is usually well-tolerated, though it can have side effects like dizziness or confusion. Overall, medical settings have used ketamine safely for pain relief.

This trial is in the early stages, so researchers are still assessing its effectiveness and safety for this specific use. However, ketamine's previous medical use provides some confidence about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for post mastectomy pain?

Unlike the standard treatments for post-mastectomy pain, which often include opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), ketamine offers a new approach by acting on the brain's NMDA receptors. Researchers are excited about ketamine because it can potentially provide rapid pain relief and reduce the risk of chronic pain developing after surgery. Additionally, ketamine's unique mechanism might help avoid some of the side effects associated with opioids, such as addiction and tolerance. This makes it a promising option for enhancing recovery and improving quality of life for patients undergoing mastectomies.

What evidence suggests that ketamine might be an effective treatment for postmastectomy pain?

This trial will compare the effects of ketamine with placebo saline for managing post-mastectomy pain. Studies have shown that ketamine can reduce pain after surgery. Research indicates that patients receiving ketamine during surgery experience less pain afterward, both short-term and long-term. Specifically, ketamine lowers the chances of developing ongoing pain months after a mastectomy (breast removal surgery). For patients at high risk of long-lasting pain after surgery, ketamine may be even more effective in reducing pain and the need for painkillers like opioids. Overall, existing evidence suggests that ketamine could be a promising option for managing post-surgical pain. ^{2 3 5 6 7}

Who Is on the Research Team?

Kristin Schreiber, MD, PhD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for women aged 18-85 scheduled for partial or total mastectomy, willing to participate in long-term follow-up and testing. It's not suitable for those only having a biopsy, pregnant, with elevated intracranial pressure (ICP), schizophrenia or bipolar disorder, an allergy to ketamine, or severe heart failure.

Inclusion Criteria

You are willing to participate in tests related to your mental and emotional well-being.

Willingness to be randomized to treatment with IV ketamine or saline during general anesthesia

Female

Exclusion Criteria

Scheduled for biopsy only

You have severe heart failure.

Pregnant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preoperative Evaluation

Participants complete demographic, medical, psychosocial, and pain questionnaires during their preoperative office visit

1 day

1 visit (in-person)

Perioperative Intervention

Participants receive a bolus and continuous infusion of ketamine or placebo during surgery

Duration of surgery

Acute Postoperative Assessment

Pain and opioid consumption are assessed in the recovery area and upon discharge

1-2 days

Inpatient stay

Follow-up

Participants are monitored for persistent pain and psychosocial factors at various intervals post-surgery

2 years

Visits at 2 weeks, 3 months, 6 months, 12 months, and 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Placebo saline

Trial Overview The study tests if ketamine can reduce pain after mastectomy better than saline. Patients receive either ketamine or saline during surgery and are monitored for pain and opioid use post-surgery and persistent pain one year later. The focus is on whether ketamine helps more in patients at high risk of chronic post-surgery pain.

How Is the Trial Designed?

Group I: unenriched Experimental Treatment 2 Interventions

all eligible women for partial or total mastectomy intervention will be ketamine or placebo saline

Group II: enriched for PPMP risk Experimental Treatment 2 Interventions

women at high risk for persistent pain after partial or total mastectomy intervention will be ketamine or placebo saline

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of General Medical Sciences (NIGMS)

Collaborator

Trials

315

Recruited

251,000+

Published Research Related to This Trial

In a study of 69 gynecological surgery patients, low dose ketamine (0.15 mg/Kg) administered preoperatively did not provide a preemptive analgesic effect, as indicated by similar pain scores at rest compared to placebo.

However, patients receiving ketamine postoperatively experienced less pain upon movement on the fifth day and required less morphine in the first 6 hours, suggesting that while preemptive use is ineffective, postoperative ketamine can still improve pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. Gilabert Morell, A., Sánchez Pérez, C.[2013]

A single preoperative dose of S-ketamine (0.5 mg/kg) did not significantly reduce the incidence of chronic postsurgical pain (CPSP) or acute postoperative pain in patients undergoing video-assisted thoracoscopic surgery (VATS).

However, S-ketamine improved sleep quality on the first postoperative day compared to the placebo, while showing no significant differences in anxiety levels or adverse effects between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single Preoperative Dose of S-Ketamine Has No Beneficial Effect on Chronic Postsurgical Pain in Patients Undergoing Video-Assisted Thoracoscopic Surgical Lung Lesion Resection: A Prospective Randomized Controlled Study. Zhou, R., Zhang, Y., Tang, S., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38918160/

S-ketamine Infusion on Chronic Postoperative Pain ... We hypothesized that the incidence of CPSP would be reduced at 3 months post-breast surgery with the administration of S-ketamine compared to a placebo.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02729805

Intraoperative Ketamine on Chronic Pain After Mastectomy A recent meta-analysis of different surgeries showed that patients receiving ketamine had a modest but statistically significant reduction in incidence of ...

3. painphysicianjournal.com painphysicianjournal.com/current/pdf?article=NzAwNA%3D%3D&journal=124

Effects of Intraoperative Low-Dose Ketamine on Persistent ... Conclusions: Though intraoperative low-dose ketamine without postoperative infusion significantly reduced the incidence of PPSP up to 3 months after breast ...

4. scirp.org scirp.org/journal/paperinformation?paperid=116593

Effect of Ketamine Instillation on Acute and Chronic Post ... Ketamine instillation was effectively controlled acute post mastectomy pain in a dose-dependent manner and reduced the incidence and severity of chronic PMPS ...

5. researchgate.net researchgate.net/publication/279233430_The_Effect_of_Ketamine_Infusion_on_Post_Mastectomy_Pain_Syndrome_A_Randomized_Controlled_Study

The Effect of Ketamine Infusion on Post Mastectomy Pain ... The Effect of Ketamine Infusion on Post Mastectomy Pain Syndrome: A Randomized Controlled Study. June 2014; SECI Oncology Journal 2014. DOI: ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11985805/

Effect and safety of perioperative ketamine/esketamine ... Perioperative ketamine/esketamine administration did not significantly reduce postoperative pain in patients undergoing breast cancer surgery.

7. jpsmjournal.com jpsmjournal.com/article/S0885-3924(23)00777-7/fulltext

Efficacy and Safety of Ketamine to Treat Cancer Pain in ... There is evidence that intravenous ketamine is more suitable for controlling postoperative analgesia than subcutaneous ketamine. For example, in ...