Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04947085 |
| Other study ID # |
2020-08-05 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
October 4, 2021 |
| Est. completion date |
December 31, 2023 |
Study information
| Verified date |
November 2023 |
| Source |
Maimonides Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
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 (1). Ketamine administration in sub-dissociative doses (SDK) of 0.1-0.3 mg/kg in
pre-hospital 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 (2-4). Two commonly utilized routes of SDK administration in the ED include an
intravenous route (intravenous push dose or short infusion) and intranasal route.
In the situation when intravenous access is not readily available or unobtainable, and
intranasal route is not feasible, another non-invasive route of ketamine administration such
as inhalation via Breath-Actuated Nebulizer (BAN) is coming into the play. The BAN allows a
controlled patient-initiated delivery of analgesics in titratable fashion. Nebulized
administration of ketamine has been studied in the areas of acute postoperative pain
management (post-intubational sore throat), in anesthesia (pre-medication for general
anesthesia,) and in managing cancer pain, and status asthmaticus therapy.
However, our research team has published a case series of 5 patients receiving nebulized
ketamine for a variety of acute painful conditions and has recently completed a randomized
double-blind trial of 120 adult patients that evaluated analgesic efficacy and safety of
nebulized ketamine at three different dosing regimens for acute pain in the ED. Currently, we
are conducting two additional studies evaluating the role of nebulized ketamine in pediatric
ED and pre-hospital arena.
In this study the investigators hypothesize that intravenous sub-dissociative-dose ketamine
of 0.3 mg/kg will provide better analgesia at 30 min post-medication administration in
comparison to nebulized ketamine administered at 0.75 mg/kg. The primary outcome of this
trial is the comparative reduction in participant's pain scores at 30 minutes post medication
administration.
Description:
Design: This is a prospective, randomized, double-blind, double dummy trial comparing
analgesic efficacy and safety of intravenous SDK administered at 0.3 mg/kg over 15 minutes to
nebulized ketamine at 0.75mg/kg administered via BAN to patients presenting to the ED of
Maimonides Medical Center with acute and chronic painful conditions. Upon meeting the
eligibility criteria, patients will be randomized into two study groups: IV SDK and Nebulized
K-BAN.
Subjects: Patients 18 years of age and older presenting to the ED with acute and chronic
painful conditions such as traumatic and non-traumatic abdominal, flank, back,
musculoskeletal pain, headache, as well as exacerbation of chronic abdominal, musculoskeletal
and neuropathic pain with a score of 5 or more on a standard 11- point (0 to 10) numeric
rating scale and requiring parenteral analgesia as determined by the treating attending
physician. Patients' screening and enrollment will be performed by study investigators and
research assistants. All patients will be enrolled at various times of the day when study
investigators will be available for patient enrollment and an ED pharmacist will be available
for medication preparation
Data Collection Procedures: Each patient will be approached by a study investigator for
acquisition of written informed consent and Health Insurance Portability and Accountability
Act authorization after being evaluated by the treating emergency physician and determined to
meet study eligibility criteria. When English will not be the participant's primary language,
a language- appropriate consent form will be used and non-investigator, hospital-employed,
trained interpreters or licensed telephone interpreter will assist in acquisition of informed
consent. 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.
A study investigator will record the patient's body weight and baseline vital signs.
The on-duty ED pharmacist will prepare either a breath-actuated nebulizer with a dose of 0.75
mg/kg or an infusion dose of IV SDK at 0.3 mg/kg in 100 ml normal saline bag according to the
predetermined randomization list, which will be created in SPSS (version 24; IBM Corp,
Armonk, NY) with block randomization of every 10 participants. All participants will receive
a corresponding placebo in order to maintain double-dummy design: the subjects randomized to
receive IV SDK will also receive nebulized saline via BAN, and the subjects receiving K-BAN
will also receive an IV infusion of Normal Saline over 15 minutes. The medication will be
delivered to the treating nurse in a blinded fashion who will set up an infusion pump with a
run time of 15 minutes. The nebulization of active drug and placebo via BAN will have a
minimum time of 5 min and maximum time of 15 min.
Study investigators will record pain scores, vital signs, and adverse effects at 15, 30, 60,
90, and 120 minutes. If patients reported a pain numeric rating scale score of 5 or greater
and requested additional pain relief, intravenous morphine at 0.1 mg/kg will be administered
as a rescue analgesic.
The preparing ED pharmacist, research manager, and statistician will be the only ones with
knowledge of the study arm to which each participant would be randomized. Treating providers,
participants, and the data collecting research team will be blind to the medication route
received.
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. Development of the randomization list, confirmation of written consent
acquisition for all participants, and statistical analyses will be conducted by the research
administrator and/or statistician who will work independently of any data collection.
Patients will be closely monitored for any change in vital sings and for adverse effects
during the entire study period (up to 120 minutes) by study investigators. Common adverse
effects that are associated with sub-dissociative dose ketamine are felling of unreality,
dizziness, nausea, vomiting, and sedation.
