Nebulized Ketamine vs Fentanyl for Acute Pain
(KETAFEN Trial)
Recruiting in Palo Alto (17 mi)
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Antonios Likourezos
Must not be taking: Opioids, NSAIDs
Disqualifiers: Pregnancy, Head injury, Unstable vitals, others
No Placebo Group
Prior Safety Data
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?In situations where intravenous access is not readily available or is unobtainable and the intranasal route is not feasible, another non-invasive route of ketamine administration, such as inhalation via breath-actuated Nebulizer (BAN), is becoming a viable alternative. The BAN allows the controlled, patient-initiated delivery of analgesics in a measured and titratable fashion. (18) Ketamine has been studied as a nebulized drug in a lot of different settings and for a lot of different reasons, such as to treat acute pain after surgery (like a sore throat after being intubated), as a pre-medication for general anesthesia, to treat cancer pain, and as a therapy for asthmaticus.
Our research team has published two case series of 10 adult patients who were given nebulized ketamine (via BAN) for a variety of acute traumatic and non-traumatic painful conditions. The patients showed a 60% decrease in pain and a small number of side effects. Furthermore, our group published a randomized, double-blind trial of 120 adult patients evaluating the analgesic efficacy and safety of nebulized ketamine at three different dosing regimens for acute pain in the ED (0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg), showing similar analgesic efficacy between the three different dosing regimens for short-term (up to 120 minutes) pain relief. Lastly, we recently completed a randomized, double-blind, double-dummy clinical trial comparing the analgesic efficacy and safety of nebulized ketamine and intravenous ketamine in managing acute pain in adult ED patients, with data currently being analyzed.
Nebulized fentanyl given in the ED to adults with acute traumatic and non-traumatic pain syndromes at a dose range of 1.5-4 mcg/kg showed the same or even better pain-relieving effects than IV fentanyl and IV morphine alone.
Our objective is to compare the analgesic efficacy and rates of side effects of a 0.75 mg/kg dose of ketamine administered via breath-actuated nebulizer (BAN) to a dose of 3 mcg/kg of fentanyl administered via breath-actuated nebulizer (BAN) in adult patients presenting to the ED with acute painful conditions.
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 data supports the effectiveness of the drug Nebulized Ketamine for acute pain?
Research shows that nebulized ketamine can effectively reduce pain in emergency department patients with acute traumatic pain, as seen in a case series where all patients experienced pain relief after receiving the drug.
12345Is nebulized ketamine safe for managing acute pain?
Research shows that low-dose ketamine, whether given intravenously or through a nebulizer, is generally safe for managing acute pain, with no significant adverse events reported in studies comparing it to fentanyl.
12567How does nebulized ketamine differ from other drugs for acute pain?
Nebulized ketamine is unique because it is administered through inhalation, which can be more convenient and less invasive than intravenous methods. It provides effective pain relief in sub-dissociative doses, making it a novel option for managing acute pain in emergency settings.
15678Eligibility Criteria
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
I am fully aware of who I am, where I am, and the current time.
Demonstrated understanding of the informed consent process and content
I can describe any side effects I experience.
+4 more
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)
I am unable to give consent by myself.
+7 more
Trial Timeline
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)
Participant Groups
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.
2Treatment groups
Active Control
Group I: Nebulized KetaBANActive Control1 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 FentaBANActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Maimonides Medical CenterBrooklyn, NY
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Who Is Running the Clinical Trial?
Antonios LikourezosLead Sponsor
References
Intranasal ketamine for acute pain management in children: A systematic review and meta-analysis. [2021]To assess the efficacy and safety of intranasal analgesic-dose ketamine as compared to intranasal fentanyl for pediatric acute pain.
Analgesic Efficacy of Intranasal Ketamine Versus Intranasal Fentanyl for Moderate to Severe Pain in Children: A Prospective, Randomized, Double-Blind Study. [2023]This study aimed to compare analgesic efficacy of intranasal (IN) ketamine to IN fentanyl for moderate to severe pain in children in a pediatric emergency department.
Randomized Controlled Feasibility Trial of Intranasal Ketamine Compared to Intranasal Fentanyl for Analgesia in Children with Suspected Extremity Fractures. [2019]We compared the tolerability and efficacy of intranasal subdissociative ketamine to intranasal fentanyl for analgesia of children with acute traumatic pain and investigated the feasibility of a larger noninferiority trial that could investigate the potential opioid-sparing effects of intranasal ketamine.
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. [2022]We compare the analgesic effectiveness of intranasal fentanyl and ketamine in children.
Administration of Nebulized Ketamine for Managing Acute Pain in the Emergency Department: A Case Series. [2020]Ketamine administration in sub-dissociative doses in the emergency department (ED) results in effective pain relief in patients with acute traumatic and non-traumatic pain, chronic pain, and opioid-tolerant pain. This case series describes five adult ED patients who received nebulized ketamine for predominantly acute traumatic pain. Three patients received nebulized ketamine at 1.5 milligrams per kilogram (mg/kg) dose, one patient at 0.75 mg/kg, and one patient at 1 mg/kg. All five patients experienced a decrease in pain from the baseline up to 120 minutes. The inhalation route of ketamine delivery via breath-actuated nebulizer may have utility for managing pain in the ED.
Intravenous Low-Dose Ketamine Provides Greater Pain Control Compared to Fentanyl in a Civilian Prehospital Trauma System: A Propensity Matched Analysis. [2020]Objective: A few studies report comparable analgesic efficacy between low-dose ketamine and opioids such as morphine or fentanyl; however, limited research has explored the safety and effectiveness of intravenous low-dose ketamine as a primary analgesic in a civilian prehospital setting. The objective of this study is to compare pain control between low-dose ketamine and fentanyl when administered intravenously (IV) for the indication of severe pain. Methods: This was a retrospective, observational review of prehospital adult patients (≥18 years) who presented with severe pain (numeric rating scale, 7-10) and were treated solely with either low-dose ketamine IV or fentanyl IV between January 1, 2014 and December 31, 2016. Propensity matched analysis was performed adjusting for all baseline variables with p ≤ 0.10 and for baseline pain score to match ketamine and fentanyl patients on a one-to-one ratio. The primary outcome was change in pain score from baseline to after treatment and evaluated with a paired t-test. Secondary outcomes were changes in vital signs and Glasgow coma scale (GCS) from baseline to after treatment, as well as incidence of clinically significant adverse events (AEs); AEs were followed from scene arrival through emergency department discharge. Results: Propensity matched analysis produced 79 matched pairs. Ketamine IV patients, receiving a mean (SD) dose of 0.3 (0.1) mg/kg, showed a significantly larger mean decrease in pain after treatment, compared to the fentanyl IV patients (-5.5 (3.1) vs. -2.5 (2.4), p < 0.001). A significantly greater proportion of patients receiving ketamine IV achieved at least a 50% reduction in pain compared to those receiving fentanyl IV (67% vs. 19%, p < 0.001), marking 52 ketamine IV patients as responders to treatment. Vital signs demonstrated a nonsignificant decrease in blood pressure, respiratory rate, heart rate, and GCS. No clinically significant AEs were reported for patients receiving ketamine IV. Conclusion: The significant reduction in pain, significantly high proportion of ketamine responders, and the lack of clinically significant AEs characterizing patients receiving low-dose ketamine IV compared to fentanyl IV, all provide further support for its use as an effective prehospital analgesic. Level of Evidence: Level III, therapeutic.
Intranasal Ketamine as an Adjunct to Fentanyl for the Prehospital Treatment of Acute Traumatic Pain: Design and Rationale of a Randomized Controlled Trial. [2021]Objective: Acute pain management is fundamental in prehospital trauma care. Early pain control may decrease the risk of developing post-traumatic stress disorder (PTSD) and chronic pain. Fentanyl and ketamine are frequently used off-label, but there is a paucity of comparative data to guide decision-making about treatment of prehospital severe, acute pain. This trial will determine whether the addition of single dose of intranasal ketamine to fentanyl is more effective for the treatment of acute traumatic pain than administration of fentanyl alone.Methods: This two-part study consists of prehospital and 90-day follow-up components (NCT02866071). The prehospital trial is a blinded, randomized, controlled trial of adult men (age 18-65 years) rating pain ≥7/10 after an acute traumatic injury of any type. Women will be excluded due to inability to confirm pregnancy status and unknown fetal risk. Paramedics will screen patients receiving standard of care fentanyl and, after obtaining standard informed consent, administer 50 mg intranasal ketamine or matching volume saline as placebo. Upon emergency department (ED) arrival, research associates will serially assess pain, concomitant treatments, and adverse side effects. Enrolled subjects will be approached for consent to participate in the 90-day follow-up study to determine rates of PTSD and chronic pain development. The primary outcome of the prehospital study is reduction in pain on the Verbal Numerical Rating Scale between baseline and 30-minutes after study drug administration. The proportion achieving a reduction of ≥2-points will be compared between study arms using a Chi-square test. Secondary outcomes of the prehospital trial include reduction in reported pain at the time of ED arrival and at 30 minutes intervals for up to three hours of ED care, the incidence of adverse events, and additional opiate requirements prior to ED arrival and within the first three hours of ED care. The outcomes in the follow-up study are satisfaction with life and development of PTSD or chronic pain at 90 days after injury. An intention-to-treat approach will be used.Conclusion: These studies will test the hypotheses that ketamine plus fentanyl, when compared to fentanyl alone, effectively manages pain, decreases opiate requirements, and decreases PTSD at 90 days.
Randomized clinical trial of nebulized fentanyl citrate versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain. [2022]To compare the pain relief achieved with nebulized fentanyl citrate with intravenous (i.v.) fentanyl citrate in children presenting to the emergency department (ED) with painful conditions to determine if nebulized fentanyl is a feasible alternative to i.v. fentanyl for the treatment of acute pain in children.