Ketamine vs Fentanyl for Traumatic Injury Pain Management

(PAIN Trial)

Recruiting at 8 trial locations

Overseen By Jason Sperry, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Jason Sperry

Disqualifiers: No IV access, Age <18, others

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

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

994 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two pain medications, ketamine and fentanyl, to determine which provides better relief for individuals with traumatic injuries needing pain management before hospital arrival. The goal is to identify which drug offers superior pain control and outcomes for patients in compensated shock. The trial seeks participants who have sustained serious injuries and require immediate strong pain medication. Individuals being transported to a participating trauma center may be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, allowing participants to contribute to potentially groundbreaking pain management solutions.

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 is 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 ketamine is often used to treat severe pain, such as pain from injuries or broken bones. Studies have found that low doses can provide strong pain relief. Although ketamine is effective, it can sometimes cause side effects like hallucinations or dizziness. However, these side effects are usually mild and short-lived.

Fentanyl is another well-known painkiller, especially used in hospitals. It is very strong and provides effective pain relief. Like ketamine, fentanyl can also cause side effects, such as nausea, dizziness, or drowsiness.

Both ketamine and fentanyl are commonly used to manage pain and are considered safe when administered by a doctor. This trial aims to compare these two treatments to determine which one more effectively relieves pain in patients with injuries. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for traumatic injury pain management because they offer unique approaches compared to traditional options like morphine or other opioids. Ketamine Hydrochloride stands out due to its unique mechanism of action, as it blocks NMDA receptors, potentially providing pain relief without the respiratory depression commonly associated with opioids. Fentanyl Citrate, a potent opioid, has been a standard in pain management, but when compared head-to-head with ketamine in this trial, researchers hope to better understand their relative effectiveness and safety profiles. By comparing these treatments, the goal is to identify options that not only alleviate pain effectively but also minimize side effects, offering a more comprehensive approach to patient care.

What evidence suggests that this trial's treatments could be effective for traumatic injury pain management?

This trial will compare Ketamine Hydrochloride and Fentanyl Citrate for managing pain from traumatic injuries. Research has shown that ketamine is a strong option for severe pain management, such as pain from injuries, and studies indicate it can be as effective as morphine for quick pain relief in emergencies. This is particularly useful when reducing opioid use, like morphine, is important. Fentanyl, another well-known pain reliever, is often used in emergencies because it quickly eases severe pain. Both treatments have proven effective, making them good options for managing pain from traumatic injuries. ^{1 3 4 6 7}

Who Is on the Research Team?

Jason Sperry, MD, MPH

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

The PAIN trial is for trauma patients with compensated shock (SI>0.9) who need IV pain medication and are being transported to a LITES Trauma center. It's not for those under 18, women under 50, anyone with high blood pressure (SBP>180 mmHg), prior pain meds or advanced airway management, prisoners, allergy to the drugs tested, or if they or family object.

Inclusion Criteria

I was taken to a PAIN Trauma center immediately after my injury.

I needed strong pain medication through an IV because of severe pain before getting to the trauma center.

Patient with compensated shock as defined by Shock Index (SI) >0.9

Exclusion Criteria

I am a woman under 50 years old.

Wearing a 'NO PAIN STUDY' bracelet

I or a family member have expressed concerns about participating in the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prehospital Treatment

Participants receive prehospital administration of ketamine hydrochloride or fentanyl citrate for pain management

Immediate

1 visit (prehospital)

Hospitalization

Participants are monitored and treated in the hospital following prehospital intervention

Up to 30 days

Follow-up

Participants are monitored for long-term outcomes including opioid use and pain assessment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Fentanyl Citrate
• Ketamine Hydrochloride

Trial Overview This study tests how effective ketamine hydrochloride is compared to fentanyl citrate in managing pain for prehospital trauma patients with shock. Patients will be randomly assigned one of these medications without knowing which one they're getting during their transport to the hospital.

How Is the Trial Designed?

Group I: Ketamine Hydrochloride Experimental Treatment 1 Intervention

2 blinded doses 2.5mg/ml ketamine hydrochloride in separately sealed pre-filled syringes Subjects will be administered the first dose over approximately 2 minutes via slow IV push. Pain assessment following administration will be obtained and recorded every 15 minutes. Redosing may occur after approximately 15 minutes if the subject has a qualifying pain score, there are no contraindications to pain medication per local protocol, and no exclusion criteria have been met.

Group II: Fentanyl Citrate Active Control 1 Intervention

2 blinded doses 10mcg/ml in separately sealed pre-filled syringes Subjects will be administered the first dose over approximately 2 minutes via slow IV push. Pain assessment following administration will be obtained and recorded every 15 minutes. Redosing may occur after approximately 15 minutes if the subject has a qualifying pain score, there are no contraindications to pain medication per local protocol, and no exclusion criteria have been met.

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

Approved in United States as Fentanyl Citrate for:

• Severe pain
• Chronic pain
• Breakthrough pain
• Preoperative anesthesia
• Postoperative pain

Approved in European Union as Fentanyl for:

• Severe pain
• Chronic pain
• Breakthrough pain
• Preoperative anesthesia
• Postoperative pain

Approved in Canada as Fentanyl Citrate for:

• Severe pain
• Chronic pain
• Breakthrough pain
• Preoperative anesthesia
• Postoperative pain

Who Is Running the Clinical Trial?

Jason Sperry

Lead Sponsor

Trials

9

Recruited

6,900+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

In a study of 213 U.S. service members with serious combat injuries, those treated with prehospital ketamine had significantly lower odds of developing PTSD in the first year post-injury, particularly among patients without traumatic brain injury (TBI).

Despite fewer patients receiving ketamine compared to opioids, those who did had more severe injuries, yet the use of ketamine was associated with better PTSD outcomes, suggesting it may be a beneficial alternative to opioids in combat casualty care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Prehospital Ketamine Associated With a Change in the Prognosis of PTSD? Melcer, T., Walker, GJ., Dye, JL., et al.[2022]

In a study of 79 matched pairs of adult patients with severe pain, low-dose intravenous ketamine resulted in a significantly greater reduction in pain compared to intravenous fentanyl, with a mean decrease of -5.5 versus -2.5 on the pain scale.

Patients receiving ketamine also had a higher response rate, with 67% achieving at least a 50% reduction in pain, and no clinically significant adverse events were reported, suggesting that ketamine is a safe and effective option for prehospital pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Low-Dose Ketamine Provides Greater Pain Control Compared to Fentanyl in a Civilian Prehospital Trauma System: A Propensity Matched Analysis. Bronsky, ES., Koola, C., Orlando, A., et al.[2020]

In a study of 60 pediatric patients undergoing extracorporeal shock wave lithotripsy (ESWL), the ketamine-fentanyl (KF) combination demonstrated better hemodynamic stability and fewer side effects compared to the ketamine-midazolam (KM) combination.

Both groups had similar recovery and discharge times, but the KF group reported lower pain levels and better overall comfort during the procedure, indicating it may be a more effective anesthetic option for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Ketamine with Midazolam versus Ketamine with Fentanyl for Pediatric Extracorporeal Shock Wave Lithotripsy Procedure: A Randomized Controlled Study. Akelma, H., Kiliç, ET., Salik, F., et al.[2022]

This study aims to evaluate whether adding intranasal ketamine to fentanyl improves pain management in adults with severe acute trauma, potentially reducing the need for additional opioids and the risk of developing PTSD.

The trial will assess pain reduction within 30 minutes of treatment and follow participants for 90 days to monitor for PTSD and chronic pain, providing valuable data on the efficacy and safety of this combined treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Ketamine as an Adjunct to Fentanyl for the Prehospital Treatment of Acute Traumatic Pain: Design and Rationale of a Randomized Controlled Trial. McMullan, J., Droege, C., Strilka, R., et al.[2021]

This study is the first randomized controlled trial comparing the effectiveness of intranasal (IN) ketamine and IN fentanyl for treating moderate to severe pain in children with isolated musculoskeletal limb injuries, involving participants aged 3 to 13 years.

If IN ketamine is found to be equally effective as IN fentanyl, it could offer an additional safe and effective option for acute pain relief in pediatric emergency settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PICHFORK (Pain InCHildren Fentanyl OR Ketamine) trial comparing the efficacy of intranasal ketamine and fentanyl in the relief of moderate to severe pain in children with limb injuries: study protocol for a randomized controlled trial. Graudins, A., Meek, R., Egerton-Warburton, D., et al.[2021]

In a systematic review of five randomized controlled trials, ketamine was found to provide similar pain relief compared to fentanyl for pediatric orthopedic emergencies, with no significant differences in pain scores at 15 to 30 minutes after administration.

However, ketamine was associated with a higher risk of side effects, including increased nausea and dizziness, suggesting that while it may be effective, its safety profile needs careful consideration in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of ketamine versus fentanyl on pain relief for pediatric orthopedic emergencies: A meta-analysis of randomized controlled studies. Qiu, J., Xie, M.[2023]

A case report demonstrated that nebulized ketamine delivered via a breath-actuated nebulizer significantly reduced a patient's pain from 8/10 to 3/10 after a traumatic ankle injury, indicating its efficacy as an analgesic in the prehospital setting.

Nebulized ketamine may be a valuable alternative to opioids for pain management in acute traumatic limb injuries, especially for patients with challenging IV access or when opioid-sparing options are desired.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebulized Ketamine Used for Managing Ankle Fracture in the Prehospital Emergency Setting: A Case Report. Quinn, E., Dhanraj, S., Liu, J., et al.[2023]

In a study of 63 patients requiring procedural sedation in the emergency department, subdissociative-dose ketamine was found to be significantly safer than fentanyl, with fewer cardiorespiratory events occurring during sedation.

Both ketamine and fentanyl provided similar efficacy in sedation, but patients receiving fentanyl experienced more serious intrasedation events, with 83.9% of fentanyl patients having events compared to only 46.9% of those receiving ketamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subdissociative-dose ketamine versus fentanyl for analgesia during propofol procedural sedation: a randomized clinical trial. Messenger, DW., Murray, HE., Dungey, PE., et al.[2022]

This pilot trial will assess the safety and efficacy of intranasal subdissociative (INSD) ketamine compared to intranasal fentanyl in 80 children aged 4-17 with acute pain from suspected extremity fractures, focusing on side effects and pain reduction.

The study aims to explore whether INSD ketamine can reduce overall opioid use during emergency department stays, potentially offering a safer alternative to traditional opioid analgesics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department. Reynolds, SL., Studnek, JR., Bryant, K., et al.[2018]

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. 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 ...

3. 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 ...

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

Intranasal ketamine for acute traumatic pain in the Emergency ... Pain relief and adverse effects were recorded for 1 h post-administration. The primary outcome was efficacy of IN ketamine compared to IV and IM ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4014022/

Ketamine for chronic pain: risks and benefits - PMC Low dose ketamine produces strong analgesia in neuropathic pain states, presumably by inhibition of the N-methyl-D-aspartate receptor.

7. reference.medscape.com reference.medscape.com/drug/ketalar-ketamine-343099

Ketalar (ketamine) dosing, indications, interactions ... Medscape - Indication-specific dosing for Ketalar (ketamine), frequency-based adverse effects, comprehensive interactions, contraindications, ...