Ketamine for Postoperative Pain

(KALPAS Trial)

Not currently recruiting at 17 trial locations

Overseen By Simon Haroutounian, PhD, MSc

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: NYU Langone Health

Must not be taking: Lamotrigine, Alfentanil

Disqualifiers: Cognitive impairment, Schizophrenia, Hypertension, 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: 1

Duration: Up to 6 hours intraoperatively and 2 hours postoperatively

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of ketamine, an anesthetic, in reducing long-term pain after breast surgery. Participants are divided into three groups: one receives a continuous ketamine drip during surgery, another receives a single dose afterward, and the last group receives a placebo, an inactive treatment. Women undergoing elective mastectomy for cancer or prevention, without cancer spread, may be eligible if they do not have certain health issues such as high blood pressure or a history of drug misuse. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking pain management solutions.

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.

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

Research has shown that ketamine is generally safe and effective for managing sudden pain after surgery. However, some side effects, such as potential memory issues and concerns about nervous system harm, have been noted. Studies have found that patients using ketamine for pain relief might experience these effects, but they are usually mild. Ketamine has been used in various settings, including hospitals, and the FDA has approved it for certain uses, suggesting it is safe when used correctly. While ketamine effectively reduces pain, considering these possible side effects is important when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using ketamine for postoperative pain because it offers a unique approach compared to traditional painkillers like opioids. Ketamine works by blocking NMDA receptors in the brain, which helps manage pain and can reduce the need for opioids, minimizing the risk of addiction. Moreover, the trial explores different administration methods, such as continuous infusion and a single-dose approach, which could offer more flexible pain management tailored to patient needs. This could lead to faster pain relief and fewer side effects, making recovery smoother for patients after surgery.

What evidence suggests that this trial's treatments could be effective for reducing chronic post-mastectomy pain?

Research has shown that ketamine can help reduce pain after surgery. In this trial, participants will be assigned to different treatment arms to evaluate its effectiveness. One group will receive a continuous ketamine infusion, which studies have found effectively manages pain and decreases the need for opioids, strong painkillers, after surgery. For instance, it improved pain relief during surgeries like gallbladder removal. Another group will receive a single dose of ketamine, which has been effective in managing sudden pain, with reviews noting lower pain levels and less need for opioids. Both methods of administering ketamine have been linked to better pain control and less discomfort after surgery. These findings suggest that ketamine could also help manage long-term pain after surgeries like mastectomies. ^{2 6 7 8 9}

Who Is on the Research Team?

Lisa Doan, MD

Principal Investigator

NYU Langone Health

Jing Wang, MD, PhD

Principal Investigator

NYU Langone Health

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Ketamine + Saline
• Placebo

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.

How Is the Trial Designed?

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 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?

NYU Langone Health

Lead Sponsor

Trials

1,431

Recruited

838,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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]

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]

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 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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4606413/

Role of Ketamine in Acute Postoperative Pain Management In a number of limited situations, ketamine has shown some efficacy in controlling postoperative pain and decreasing opioid consumption.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26949390/

Ketamine Infusion for Postoperative Pain Control: A ... Continuous S(+)-ketamine infusion during laparoscopic cholecystectomy under target-controlled intravenous anesthesia provided better postoperative pain control ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07059429

Study Details | NCT07059429 | Ketamine Administration for ... This study is conducted to evaluate the effectiveness and safety of ketamine infusion for pain relief after knee replacement surgery.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0952818024003192

Oral ketamine for acute postoperative analgesia (OKAPA) ... This pilot study demonstrated that low dose oral ketamine can be safely used as an adjunct in postoperative pain treatment to help reduce opioid consumption.

5. mdpi.com mdpi.com/2077-0383/13/24/7699

The Impact of Ketamine on Outcomes in Acute Pain ... Evidence shows that intravenous ketamine reduces the pain intensity, postoperative opioid use, and the risk of vomiting and nausea while improving analgesia.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9308221/

ketamine hydrochloride injection for postoperative acute pain ... The secondary endpoints include the time of first use of rescue analgesics after surgery, rescue analgesia rate within 48 h after surgery, ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1366007107001672

Safety and efficacy of intranasal ketamine for acute ... We evaluated the safety and analgesic efficacy of intranasal ketamine in treating moderate-to-severe, acute postoperative pain in the molar extraction model.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04834427

Safety and Efficacy Evaluation of S (+) - Ketamine in Children Objective: To evaluate the analgesic effect of perioperative administration of S (+) - ketamine on postoperative acute pain in children undergoing surgery, and ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/016812s040lbl.pdf

ketamine - accessdata.fda.gov WHEN KETALAR IS USED ON AN OUTPATIENT BASIS, THE PATIENT SHOULD NOT BE RELEASED. UNTIL RECOVERY FROM ANESTHESIA IS COMPLETE AND THEN SHOULD BE ACCOMPANIED BY. A ...