Clinical Trial Details
— Status: Withdrawn
Administrative data
NCT number |
NCT04162028 |
Other study ID # |
2018-10-08 |
Secondary ID |
|
Status |
Withdrawn |
Phase |
Phase 4
|
First received |
|
Last updated |
|
Start date |
January 15, 2019 |
Est. completion date |
July 28, 2021 |
Study information
Verified date |
July 2021 |
Source |
Maimonides Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
In the situation when intravenous access is not readily available or unobtainable, or when
prehospital delays to obtain intravenous access are not warranted, sub-dissociative dose
ketamine can be administered via intranasal (IN) route. The data supporting IN is not set on
the optimum intranasal dose (range 0.75-1 mg/kg) and frequencies of administration. In
addition, IN administration of SDK for adult patients in the ED requires a highly
concentrated solution that is not routinely stock in the ED. Hence, another non-invasive
route exists such as nebulization via a Breath-Actuated Nebulizer which allows a controlled
patient-initiated delivery of analgesics in titratable fashion.
Nebulized administration of ketamine however, has only been studied in the areas of acute
postoperative pain management, cancer palliation, and status asthmaticus therapy (ref). To
our knowledge, there are no prospective randomized trials that evaluated a role of nebulized
SDK role in managing acute pain due to extremity trauma in the prehospital arena.
We aim to evaluate analgesic efficacy and safety of sub-dissociative dose ketamine
administered prehospital via breath-actuated nebulizer at 1.0 mg/kg for patients with acute
traumatic extremity injuries.
Description:
Ketamine is a non-competitive N-methyl-D-aspartate (NMDA)/glutamate receptor complex
antagonist that decreases pain by diminishing central sensitization, hyperalgesia, and
"wind-up" phenomenon at the level of the spinal cord (dorsal ganglion) and central nervous
system Ketamine administration in sub-dissociative doses (0.1-0.3 mg/kg) in prehospital
settings and in the ED results in effective pain relief in patients with acute traumatic and
non-traumatic pain, chronic non-cancer and cancer pain, and in patients with opioid-tolerant
pain by virtue of providing anti-hyperalgesia, anti-allodynia, and anti-tolerance. Two
commonly employed strategies of SDK administration in the ED include an intravenous push
(IVP) dose (over 2-5 minutes), which is associated with relatively high rates of minor but
bothersome psycho-perceptual side effects (feeling of unreality and dizziness), or short
infusion (SI) given over 15 minutes with significantly reduced rates of unreality and
preserved analgesic efficacy.
In the current study the investigators hypothesize that sub-dissociative-dose ketamine
administered as a single agent via breath actuated nebulizer at the dose of 1.0 mg/kg will
provide significant pain relief with minimal rates of side effects for patients with acute
traumatic extremity injuries and will allow for alternative administration of effective
analgesia especially in those settings for which intravenous or intraosseous routes are
difficult or not necessary or when a delay in patient transport to a hospital is not ideal.
The primary outcome of this trial is the percent reduction in participant's pain scores at 30
minutes post medication administration.
STUDY DESIGN
Subjects: Patients 18 years of age and older transported by prehospital care providers to the
ED with acute traumatic extremity injuries with a pain score of 5 or more on a standard 11-
point (0 to 10) numeric rating scale. Patients will be enrolled by Emergency Medical Services
(EMS) providers of Maimonides Medical Center (MMC) who are operating under the New York City
9-1-1 Regional Emergency Medical Advisory Committee (REMAC) auspices. Patient screening,
enrollment, and data collection will be performed initially by advanced life support (ALS)
paramedics and subsequently completed by study investigators upon arrival to the MMC
emergency department. Emergency department pharmacist investigators will prepare PK-BAN
packages that will be assigned to every ALS ambulance at the start of shift. The package will
include a single ketamine 50mg/ml vial, blunt-tip needle and syringe, BAN device/tubing, and
data collection sheet.
Eligibility Criteria: Patients 18 years of age and older with acute traumatic extremities
injuries with a score of 5 or more on a standard 11- point (0 to 10) numeric rating scale.
Exclusion criteria will include altered mental status, allergy to ketamine, pregnant
patients, weight greater than 150 kg, unstable vital signs (systolic blood pressure <90
or>180 mm Hg, pulse rate <50 or >150 beats/min, and respiration rate <10 or >30 breaths/min),
and past medical history of alcohol or drug abuse, or schizophrenia.
Design: This is a prospective, observational study evaluating analgesic efficacy and safety
of sub-dissociative dose ketamine of 1.0 mg/kg administered via breath-actuated nebulizer
Data Collection Procedures: Each patient will be approached by advanced life support (ALS)
paramedics for acquisition of written informed consent and Health Insurance Portability and
Accountability Act authorization after meeting study eligibility criteria. In case of severe
pain (extremis), a verbal consent will suffice the initial administration of the SDK with
subsequent signing of the informed consent upon arrival to the ED. Baseline pain score will
be determined with an 11-point numeric rating scale (0 to 10), described to the patient as
"no pain" being 0 and "the worst pain imaginable" being 10. An ALS paramedic will record the
patient's body weight and baseline vital signs. The PK-BAN package will be opened and weight
-based dose of ketamine will be administered to the patient via BAN. The medication will be
delivered with a minimum time of 5 min and maximum time of 15 min. An ALS Paramedic record
pain scores, vital signs, and adverse effects at 15 and 30 minutes. If patients reported a
pain numeric rating scale score of 5 or greater and requested additional pain relief, a
second (equivalent to the first dose) of SDK via BAN will be administered to the patient in a
blinded fashion. In situations when nebulized SDK will fail to achieve acceptable (by
patient) pain relief or patient will refuse to continue nebulized SDK treatment, morphine at
0.1 mg/kg IV/IO/IM (not to exceed 5mg) will be administered as a rescue analgesic with an
option for one repeat dose (maximum total dose is 10mg).
All data will be recorded on data collection sheets, including patients' sex, demographics,
medical history, and vital signs and entered into SPSS (version 24.0; IBM Corp) by the
research manager. Confirmation of written consent acquisition for all participants and
statistical analyses will be conducted by the research manager and statistician, who would
work independent of any data collection.
Patients will be closely monitored for any change in vital signs and for adverse effects
during the entire study period (up to 2 hours) by study investigators after arrival to the
ED. Common adverse effects that are associated with sub-dissociative dose ketamine are
feeling of unreality, dizziness, nausea, vomiting, and sedation.