Nebulized Ketamine vs Fentanyl for Acute Pain

(KETAFEN Trial)

Overseen By Sergey Motov, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Antonios Likourezos

Must not be taking: Opioids, NSAIDs

Disqualifiers: Pregnancy, Head injury, Unstable vitals, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: 2

Duration: Up to 120 minutes

150 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments for acute pain: nebulized ketamine and nebulized fentanyl. Patients control their dosage through a device. The goal is to determine which drug offers better pain relief with fewer side effects. Ideal participants are adults experiencing moderate to severe pain who are alert and able to communicate clearly. As a Phase 4 trial, this research involves treatments already FDA-approved and proven effective, aiming to understand how they benefit more patients.

Will I have to stop taking my current medications?

The trial requires that you have not taken opioids or opioid-related medications within 4-6 hours before arriving and NSAIDs within 6 hours before arriving. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

What is the safety track record for these treatments?

Research has shown that nebulized ketamine is generally safe for treating sudden pain. An analysis of 11 different studies found no serious health issues linked to its use, and the rate of mild side effects was similar to other treatments. Another study found that nebulized ketamine provided pain relief with a safety level comparable to other methods. New evidence supports its safety and effectiveness when used in this manner.

For nebulized fentanyl, studies suggest it is as safe as painkillers administered through an IV. In some cases, it provided better pain relief than IV morphine, with relatively few side effects. Overall, both nebulized ketamine and fentanyl appear to be well-tolerated for pain relief, with minimal risk of serious side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about nebulized ketamine for acute pain because it offers a different approach compared to traditional opioids like morphine or fentanyl. Unlike opioids, which primarily work by binding to opioid receptors in the brain to block pain, ketamine acts on the NMDA receptors, providing pain relief without the typical opioid side effects like respiratory depression and addiction potential. Additionally, using a nebulized delivery method allows for rapid onset of pain relief directly through inhalation, which can be particularly beneficial in emergency settings where fast action is crucial. This combination of a novel mechanism and delivery method makes nebulized ketamine a promising alternative for managing moderate to severe pain.

What evidence suggests that this trial's treatments could be effective for acute pain?

This trial will compare nebulized ketamine and nebulized fentanyl for managing acute pain. Research has shown that nebulized ketamine effectively manages sudden pain, similar to other pain treatments. In studies, patients experienced significant pain relief with nebulized ketamine, with results comparable to ketamine given through an IV, meaning it can work just as well without needing an IV line.

For nebulized fentanyl, studies have found it provides quick and effective relief for sudden pain, sometimes even outperforming IV opioids like morphine. It also has relatively few side effects. Both treatments in this trial offer promising options for those needing fast pain relief without an IV. ^{1 2 3 5 6}

Who Is on the Research Team?

Sergey Motov, MD

Principal Investigator

Maimonides Medical Center

Are You a Good Fit for This Trial?

Adults aged 18-64 in the ED with acute pain who can rate their pain as 5 or higher on a scale, are awake and aware, understand the study's consent process, and can communicate any side effects they experience.

Inclusion Criteria

Demonstrated understanding of the informed consent process and content

I am fully aware of who I am, where I am, and the current time.

I can describe any side effects I experience.

Exclusion Criteria

I have taken opioids or NSAIDs within 6 hours before coming.

Unstable vital signs (systolic blood pressure <90 mmHg or >180 mmHg, pulse rate <50 beats/min or >150 beats/min, and respiration rate <10 breaths/min or >30 breaths/min)

Current medical history of alcohol or drug abuse

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive nebulized ketamine or fentanyl via breath-actuated nebulizer for acute pain management in the ED

Up to 120 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including pain scores and adverse effects

2 hours

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Nebulized Fentanyl
• Nebulized Ketamine

Trial Overview The trial is testing nebulized ketamine against nebulized fentanyl for emergency department patients. It aims to see which one is better at managing pain when IV access isn't available or practical.

How Is the Trial Designed?

Group I: Nebulized KetaBAN Active Control 1 Intervention

Nebulized ketamine administered at 0.75 mg/kg via BAN to adult patients presenting to the ED of Maimonides Medical Center with acute painful conditions of moderate to severe intensity.

Group II: Nebulized FentaBAN Active Control 1 Intervention

Nebulized fentanyl administered at 3 mcg/kg via BAN to adult patients presenting to the ED of Maimonides Medical Center with acute painful conditions of moderate to severe intensity.

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

Approved in United States as Ketalar for:

• Induction of anesthesia
• Maintenance of anesthesia
• Pain management
• Sedation

Approved in European Union as Ketalar for:

• Induction of anesthesia
• Maintenance of anesthesia
• Pain management
• Sedation

Approved in Canada as Ketalar for:

• Induction of anesthesia
• Maintenance of anesthesia
• Pain management
• Sedation

Who Is Running the Clinical Trial?

Antonios Likourezos

Lead Sponsor

Trials

41

Recruited

8,600+

Published Research Related to This Trial

In a study of 80 children aged 3 to 13 with moderate to severe limb pain, both intranasal fentanyl and ketamine provided similar pain relief, with median reductions of 40 mm and 45 mm respectively at 30 minutes after administration.

Ketamine was associated with a higher incidence of mild adverse events (78%) compared to fentanyl (40%), indicating that while both medications are effective, ketamine may have a higher risk of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The PICHFORK (Pain in Children Fentanyl or Ketamine) trial: a randomized controlled trial comparing intranasal ketamine and fentanyl for the relief of moderate to severe pain in children with limb injuries. Graudins, A., Meek, R., Egerton-Warburton, D., 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]

In a study involving 41 children with acute pain, nebulized fentanyl citrate (3.0 microg/kg) provided significant pain relief, with a mean decrease of 77.8 mm on the pain scale, compared to 55.1 mm for intravenous fentanyl (1.5 microg/kg).

Nebulized fentanyl was found to be a feasible alternative to intravenous fentanyl for pain management in children older than 3 years, with no adverse events reported, although younger patients had difficulties using the nebulizer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized clinical trial of nebulized fentanyl citrate versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain. Miner, JR., Kletti, C., Herold, M., et al.[2022]

In a study involving 22 children with moderate to severe pain, intranasal (IN) ketamine did not provide better pain relief compared to IN fentanyl after 20 minutes, indicating that ketamine may be less effective for acute pain management in this setting.

The ketamine group experienced significantly more adverse effects, including sedation and dizziness, with 64% of patients showing sedation compared to none in the fentanyl group, raising concerns about its safety profile in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic Efficacy of Intranasal Ketamine Versus Intranasal Fentanyl for Moderate to Severe Pain in Children: A Prospective, Randomized, Double-Blind Study. Quinn, K., Kriss, S., Drapkin, J., et al.[2023]

In a case series of five adult patients in the emergency department, nebulized ketamine provided effective pain relief for acute traumatic pain, with all patients reporting decreased pain levels within 120 minutes after administration.

The study utilized varying doses of nebulized ketamine (1.5 mg/kg, 0.75 mg/kg, and 1 mg/kg), suggesting that inhalation may be a promising method for pain management in emergency settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of Nebulized Ketamine for Managing Acute Pain in the Emergency Department: A Case Series. Drapkin, J., Masoudi, A., Butt, M., et al.[2020]

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]

Intranasal ketamine resulted in a higher frequency of minor side effects compared to intranasal fentanyl, but no serious adverse events were reported, indicating it is generally safe for use in children with acute pain.

Both ketamine and fentanyl provided similar levels of pain relief at 20 minutes, suggesting that ketamine could be a viable alternative to opioids for managing acute pain in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures. Reynolds, SL., Bryant, KK., Studnek, JR., et al.[2019]

Intranasal ketamine is effective for managing acute pain in children, showing similar pain reduction compared to intranasal fentanyl, based on a meta-analysis of 4 trials involving 276 patients.

While ketamine had a higher risk of non-serious adverse events compared to fentanyl, it did not lead to any serious adverse events, making it a potential alternative to opioids for pediatric pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal ketamine for acute pain management in children: A systematic review and meta-analysis. Oliveira J E Silva, L., Lee, JY., Bellolio, F., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27413071/

Nebulized Fentanyl in Acute Pain: A Systematic Review Conclusion: Evidence suggests that nebulized fentanyl is as effective as IV opioids in the treatment of acute pain, with relatively few adverse effects.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0735675715001928

Nebulized fentanyl vs intravenous morphine for ED ... The NF group experienced more rapid pain relief and more sustained and clinically significant pain relief over the 40-minute study interval. There were no ...

3. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/40/NCT06364540/Prot_SAP_000.pdf

Comparison of Nebulized Ketamine to Nebulized Fentanyl ... The patients showed a 60% decrease in pain and a small number of side effects (20, 21).

4. openanesthesiajournal.com openanesthesiajournal.com/VOLUME/11/PAGE/101/FULLTEXT/

Analgesic Effect of Nebulized Versus Intravenous Fentanyl ... Although nebulized fentanyl is effective in controlling pain due to limb fracture, it was less effective than intravenous type, and unable to control pain in ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/1060028016659077

Nebulized Fentanyl in Acute Pain: A Systematic Review Conclusion: Evidence suggests that nebulized fentanyl is as effective as IV opioids in the treatment of acute pain, with relatively few adverse ...

6. trialx.com trialx.com/clinical-trials/listings/292801/nebulized-ketamine-to-nebulized-fentanyl-for-treating-acute-painful-conditions-in-the-ed/

Nebulized Ketamine to Nebulized Fentanyl for Treating ... This is a prospective, randomized, double-blind trial comparing the analgesic efficacy and safety of nebulized ketamine administered at 0.75 mg/ ...