Ketamine vs Fentanyl for Traumatic Injury Pain Management
(PAIN Trial)
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Jason Sperry
Disqualifiers: No IV access, Age <18, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?The Prehospital Analgesia INtervention trial (PAIN) is a proposed 4 year (3-year enrollment) multicenter, prehospital, randomized, double-blind, clinical trial that will enroll approximately 994 patients at select LITES Network sites. The objective is to perform a prospective, interventional, randomized trial among prehospital trauma patients with compensated shock (SI≥0.9) and an indication for pain management, comparing patient centered outcomes following prehospital administration of ketamine hydrochloride versus fentanyl citrate.
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.
What data supports the effectiveness of the drug ketamine compared to fentanyl for traumatic injury pain management?
Research shows that low-dose ketamine provides greater pain control compared to fentanyl in prehospital settings, with a significant reduction in pain and a higher proportion of patients experiencing at least a 50% reduction in pain. Additionally, ketamine has been associated with fewer adverse events, supporting its effectiveness as a pain management option.
12345Is it safe to use ketamine and fentanyl for pain management in humans?
Research shows that both ketamine and fentanyl are generally safe for pain management in humans, with studies reporting no significant adverse events when used in controlled settings. Ketamine, in particular, has been noted for its effective pain relief without significant side effects in prehospital and emergency department settings.
23678How does the drug Ketamine differ from Fentanyl for traumatic injury pain management?
Ketamine, when used with Fentanyl, may provide better pain relief and reduce the need for additional opioids compared to using Fentanyl alone. Ketamine can be administered intranasally, which is a non-invasive method, and it may also help decrease the risk of developing PTSD and chronic pain after a traumatic injury.
12359Eligibility Criteria
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.
+8 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: Ketamine HydrochlorideExperimental Treatment1 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 CitrateActive Control1 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cooper University Health CareCamden, NJ
Allegheny Health Network (AHN) Allegheny General HospitalPittsburgh, PA
University of PittsburghPittsburgh, PA
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Who Is Running the Clinical Trial?
Jason SperryLead Sponsor
United States Department of DefenseCollaborator
References
Is Prehospital Ketamine Associated With a Change in the Prognosis of PTSD? [2022]Ketamine is an alternative to opioids for prehospital analgesia following serious combat injury. Limited research has examined prehospital ketamine use, associated injuries including traumatic brain injury (TBI) and PTSD outcomes following serious combat injury.
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.
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.
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. [2021]The effectiveness of intranasal (IN) fentanyl as an analgesic for painful pediatric limb injuries in the Emergency Department (ED) has been reported previously. However, efficacy of IN ketamine in sub-dissociative doses is not well studied in the ED setting. A non-blinded pilot study undertaken by this study group suggested that IN ketamine showed similar analgesic effectiveness to that reported with IN fentanyl in similar non-blinded studies. The aim of this randomized, controlled, equivalence trial is to compare the analgesic effect of sub-dissociative dose IN ketamine with IN fentanyl for children with isolated musculoskeletal limb injuries.
Influence of ketamine versus fentanyl on pain relief for pediatric orthopedic emergencies: A meta-analysis of randomized controlled studies. [2023]The comparison of ketamine with fentanyl for pain control of pediatric orthopedic emergencies remains controversial. We conduct a systematic review and meta-analysis to explore the influence of ketamine versus fentanyl on pain management among pediatric orthopedic emergencies.
Subdissociative-dose ketamine versus fentanyl for analgesia during propofol procedural sedation: a randomized clinical trial. [2022]The authors sought to compare the safety and efficacy of subdissociative-dose ketamine versus fentanyl as adjunct analgesics for emergency department (ED) procedural sedation and analgesia (PSA) with propofol.
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. [2018]Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage.
Comparison of Ketamine with Midazolam versus Ketamine with Fentanyl for Pediatric Extracorporeal Shock Wave Lithotripsy Procedure: A Randomized Controlled Study. [2022]To compare the effects of ketamine-fentanyl (KF) and ketamine-midazolam (KM) combinations on hemodynamic parameters, recovery properties, pain, and side effects in pediatric patients undergoing extracorporeal shock wave lithotripsy (ESWL) procedure.
Nebulized Ketamine Used for Managing Ankle Fracture in the Prehospital Emergency Setting: A Case Report. [2023]Acute traumatic limb injury is a common complaint of patients presenting to the emergency department (ED). Ketamine is an effective analgesic administered via intravenous (IV), intranasal (IN), intramuscular (IM), and nebulized routes in the ED. It has also been used in the prehospital setting via IV, IM, and IN routes. Recent studies have proposed the prehospital use of nebulized ketamine via breath-actuated nebulizer (BAN) as a noninvasive and effective method of analgesic delivery, as well as an alternative to opioid analgesia.