Ketamine for Postoperative Pain

(KALPAS Trial)

Recruiting at 15 trial locations

Overseen By Simon Haroutounian, PhD, MSc

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: NYU Langone Health

Must not be taking: Lamotrigine, Alfentanil

Disqualifiers: Cognitive impairment, Schizophrenia, Hypertension, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The study utilizes a 3-arm placebo-controlled RCT to study the effectiveness of ketamine in reducing chronic post-mastectomy pain. Participants randomized to the first arm will receive a 0.35 mg/kg dose after induction, followed by a 0.25 mg/kg/hr infusion during surgery (up to a maximum of 6 hours) and continued for 2 hours postoperatively. Participants in the second arm will receive a single dose of 0.6 mg/kg of ketamine in the post-anesthesia care unit, and the final group will serve as the control group and receive saline (no ketamine).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using lamotrigine, alfentanil, physostigmine, or 4-aminopyridine.

How does ketamine differ from other drugs for postoperative pain?

Ketamine is unique for postoperative pain management because it can provide both immediate and potentially long-term pain relief when administered in low doses before or during surgery. Unlike traditional pain medications, ketamine also has rapid antidepressant effects, which may help reduce depressive symptoms after surgery. ^{1 2 3 4 5}

Research Team

Lisa Doan, MD

Principal Investigator

NYU Langone Health

Jing Wang, MD, PhD

Principal Investigator

NYU Langone Health

Eligibility Criteria

This trial is for women aged 18 or older undergoing elective breast surgery without distant metastases. They must not have cognitive impairments, liver or renal insufficiency, be pregnant, in another pain study, or have certain medical conditions like uncontrolled hypertension. Participants should not be on specific medications and must have a BMI less than 41.

Inclusion Criteria

My cancer has not spread to distant parts of my body.

I am having breast surgery for cancer, which may include removing one or both breasts, lymph nodes, and possibly reconstruction.

I am a woman aged 18 or older.

Exclusion Criteria

Currently Pregnant

I am willing and able to follow all study procedures and be available for the entire study duration.

History of cognitive impairment or clinical signs of altered mental status (AMS) that may interfere with adherence to study procedures and/or participant safety. Clinical signs of AMS may include but are not limited to: confusion, amnesia, disorientation, fluctuating levels of alertness, etc.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ketamine or placebo during and after surgery, with different dosing regimens for each arm

Up to 6 hours intraoperatively and 2 hours postoperatively

Intraoperative and postoperative visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits at 1 and 7 days, and 1, 3, 6, and 12 months after surgery

Treatment Details

Interventions

• Ketamine (NMDA Receptor Antagonist)
• Ketamine + Saline (NMDA Receptor Antagonist)
• Placebo (Other)

Trial Overview The trial tests if ketamine can reduce chronic pain after mastectomy. It's a placebo-controlled study with three groups: one gets ketamine during/after surgery, another gets a single dose post-surgery, and the last group receives saline as a control.

Participant Groups

Group I: Arm 1 Continuous ketamine infusion group Active Control 1 Intervention

Continuous ketamine infusion (0.35 mg/kg after induction, followed by 0.25 mg/kg/hr until 2 hours after surgery) plus saline IV dose in post-anesthesia care unit

Group II: Arm 2 Ketamine + Saline group Active Control 1 Intervention

Saline dose and infusion intraoperatively, then single-dose IV ketamine (0.60 mg/kg) in post-anesthesia care unit plus 2 hours of saline administration after surgery

Group III: Arm 3 Placebo group Placebo Group 1 Intervention

Placebo, Saline dose and infusion intraoperatively, then saline IV dose in post-anesthesia care unit plus 2 hours of saline administration after surgery

Ketamine is already approved in Canada for the following indications:

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

In a study of 120 patients undergoing tumor resection, administering 2 or 3 escalating doses of intramuscular ketamine before surgery significantly reduced postoperative pain scores and decreased morphine consumption by about 35% compared to placebo.

The results indicate that repeated subanesthetic doses of ketamine can effectively enhance pain relief after surgery, although a single dose did not show the same benefits, and some patients experienced brief dizziness after the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repeated and escalating preoperative subanesthetic doses of ketamine for postoperative pain control in patients undergoing tumor resection: a randomized, placebo-controlled, double-blind trial. Rakhman, E., Shmain, D., White, I., et al.[2013]

This pilot study will assess the feasibility of using ketamine infusions to reduce postoperative depressive symptoms in 32 patients with a history of depression, potentially leading to a larger clinical trial.

Participants will receive either ketamine or a placebo after surgery, with depressive symptoms measured over 14 days, aiming to determine if ketamine can provide lasting antidepressant effects in the postoperative setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol for the Ketamine for Postoperative Avoidance of Depressive Symptoms (K-PASS) feasibility study: A randomized clinical trial. Fritz, BA., Tellor Pennington, BR., Palanca, BJA., et al.[2023]

A meta-analysis of six randomized controlled trials found that ketamine significantly reduces pain scores and cumulative morphine consumption in the first 24 hours after total knee arthroplasty, indicating its efficacy as a pain management option.

Ketamine also lowers the incidence of nausea and vomiting compared to placebo, without increasing the risk of thrombosis, suggesting it is a safer alternative for postoperative pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketamine reduces pain and opioid consumption after total knee arthroplasty: A meta-analysis of randomized controlled studies. Li, Z., Chen, Y.[2019]

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]

References

1. Spain pubmed.ncbi.nlm.nih.gov

[Effect of low-dose intravenous ketamine in postoperative analgesia for hysterectomy and adnexectomy]. [2013]

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

Repeated and escalating preoperative subanesthetic doses of ketamine for postoperative pain control in patients undergoing tumor resection: a randomized, placebo-controlled, double-blind trial. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Protocol for the Ketamine for Postoperative Avoidance of Depressive Symptoms (K-PASS) feasibility study: A randomized clinical trial. [2023]

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

Ketamine reduces pain and opioid consumption after total knee arthroplasty: A meta-analysis of randomized controlled studies. [2019]

5. United States 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. [2023]