Ketamine for Severe Traumatic Injury Pain Management

Overseen By Margo Mantz-Wichman, BS, RN

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Medical College of Wisconsin

Must not be taking: Opioids, MAOIs

Disqualifiers: Psychosis, Glaucoma, Hypertension, others

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if administering ketamine, a type of pain medication, to people with severe injuries immediately upon hospital entry reduces the need for opioids. Researchers will compare ketamine to a placebo (a harmless substance resembling the real treatment) to assess its effectiveness in lowering opioid use within the first two days. Patients recently injured, admitted to the hospital's trauma service, and able to start treatment within 24 hours of arrival may be suitable candidates. As an unphased trial, this study provides patients the chance to contribute to important research that could enhance pain management for future trauma patients.

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 monoamine oxidase inhibitors (a type of antidepressant).

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

Research shows that ketamine is generally safe for managing severe pain, such as pain from serious injuries. Studies have found that ketamine effectively reduces pain with fewer side effects than traditional opioid medications. For example, one study found that ketamine provided good pain relief with fewer side effects compared to opioids. Another study showed that ketamine worked as well as morphine for pain control, making it a good alternative to opioids for managing sudden, severe pain.

Some side effects may occur, such as hallucinations or unusual dreams, but these are usually manageable. If these symptoms arise, treatments like lorazepam or midazolam can help. Overall, ketamine has been well-tolerated in various situations, making it a viable option for those seeking to manage severe pain without using opioids. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for severe traumatic injury pain, which often involve opioids, ketamine offers a unique approach. Ketamine acts on the NMDA receptors in the brain, providing pain relief without the high risk of addiction associated with opioids. Researchers are excited because ketamine can be administered quickly and adjusted based on pain levels, potentially offering rapid relief. Additionally, ketamine's different mechanism could reduce side effects typical with opioids, like respiratory depression, making it a promising alternative in managing severe pain.

What evidence suggests that ketamine might be an effective treatment for severe traumatic injury pain?

In this trial, participants will join either the ketamine arm or the placebo arm. Studies have shown that ketamine, administered to those in the ketamine arm, effectively manages severe pain, including pain from injuries. Research indicates that ketamine can match morphine in pain relief, offering a viable alternative to opioids. This is particularly beneficial in injury situations, as ketamine can reduce the need for opioids, which carry their own risks. Although some studies suggest ketamine is not superior to morphine, it still provides significant pain relief. Overall, ketamine has a proven track record in treating severe pain, making it a promising option for managing pain from traumatic injuries. ^{1 3 4 6 7}

Who Is on the Research Team?

Thomas Carver, MD

Principal Investigator

Medical College of WI

Are You a Good Fit for This Trial?

This trial is for adults aged 18-64 who've been hospitalized with severe trauma (ISS >15) and can start treatment within 24 hours of arrival. It's not for those over 64, under 18, with a history of ketamine issues, chronic opioid use, substance abuse, certain heart or brain conditions, glaucoma, pregnancy, severe hypertension, prisoners or if they're on MAOIs.

Inclusion Criteria

I am admitted to the hospital for trauma care, not for orthopedic, plastic, or neurosurgery.

I can start treatment within 24 hours of arriving at the facility.

Your cancer is in advanced stages, with a high amount of cancerous cells.

Exclusion Criteria

Prisoners

Current substance abuse with opioids including prescription and/or heroin

I am currently taking MAOI medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

24 hours

Treatment

Participants receive ketamine infusion therapy or placebo for pain control

48 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Placebo

Trial Overview The study tests whether early ketamine infusion reduces the need for opioid painkillers in the first 24 to 48 hours after hospital admission compared to a placebo in adult trauma patients with significant injuries.

How Is the Trial Designed?

Group I: Ketamine arm Experimental Treatment 1 Intervention

Early ketamine infusion therapy at a rate of 3 mcg/kg/min. All ketamine infusions will be calculated based on ideal body weight (IBW), unless actual body weight is less than ideal. Ketamine infusion therapy will be continued for 48 hours. At 2-4 hours post-infusion the patient's pain will be reassessed. If the NPS is more than 5 the infusion will be increased to 5mcg/kg/min. Following each change in the infusion rate the patient's pain will be reassessed at 2-4 hours and adjustments made accordingly. Maximum infusion rate will be set at 9mcg/kg/min. Conversely, The RAAPS team should be notified if neurologic symptoms (hallucinations, delusions, disturbing dreams, vertigo) are developing and, at the discretion of the RAAPS service, a single dose of lorazepam or midazolam may be utilized. The infusion can be decreased from in 2 mcg/kg/min increments if there are symptoms believed to be related to the infusion that do not respond to benzodiazepines.

Group II: Placebo arm Placebo Group 1 Intervention

The 65 patients randomized to the control arm will receive placebo saline solution at a rate equivalent.

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?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6946038/

The Efficacy of Ketamine Administration in Prehospital Pain ... Although previous articles and reviews suggest that ketamine might effectively manage pain in trauma patients, these articles have serious limitations.

2. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK470357/

Ketamine - StatPearls - NCBI Bookshelf - NIH A wealth of evidence indicates the value of ketamine in treating severe pain, including conditions such as trauma, fractures, abdominal and ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2814327

Ketamine Compared With Morphine for Out-of-Hospital ... These findings show that ketamine was not inferior to morphine for pain control and is an opioid-reduction alternative for treatment of out-of-hospital acute ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666776225000572

Paramedic analgesia comparing ketamine and morphine ... Ketamine did not provide superior analgesia than morphine when used by paramedics to treat acute severe trauma pain.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2023/1928969

Application of Ketamine in Pain Management and the ... In addition to relieving perioperative acute pain, ketamine has also been shown to be effective in prehospital trauma care. According to a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10620013/

Ketamine in Trauma: A Literature Review and Administration ... This concluded that ketamine alone is effective and provides fewer side effects compared to opioid analgesia but offers more effective pain ...

7. bmcemergmed.biomedcentral.com bmcemergmed.biomedcentral.com/articles/10.1186/s12873-016-0107-0

Intranasal ketamine for acute traumatic pain in the Emergency ... This prospective, open label, single-center, randomized clinical trial was designed to assess the efficacy and safety of IN ketamine in the ED setting.