Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pre-hospital Nebulized Ketamine for Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04162028
Recruitment Status : Withdrawn (Investigators not interested any more in the study)
First Posted : November 13, 2019
Last Update Posted : July 30, 2021
Sponsor:
Information provided by (Responsible Party):
Antonios Likourezos, Maimonides Medical Center

Tracking Information
First Submitted Date  ICMJE November 4, 2019
First Posted Date  ICMJE November 13, 2019
Last Update Posted Date July 30, 2021
Actual Study Start Date  ICMJE January 15, 2019
Actual Primary Completion Date July 28, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 12, 2019)
Change in Pain Scores [ Time Frame: 30 minutes ]
The primary outcome will include a percentage of patients achieving a 20% or greater change in pain scores on numeric rating pain scale (NRS) ranging form 0 no pain to 20 severe pain for the baseline to 30 minutes post-analgesic administration.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 12, 2019)
Rescue Analgesia [ Time Frame: 30 minutes ]
The secondary outcomes will include a need for second or third dose, a need for rescue analgesia at either 15 and 30 minutes
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pre-hospital Nebulized Ketamine for Pain
Official Title  ICMJE Pre-hospital Utilization of Nebulized Sub-dissociative Dose Ketamine for Managing Acute Traumatic Extremity Pain: a Prospective Observational Study
Brief 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.

Detailed 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pain
Intervention  ICMJE Drug: Nebutlized Ketamine
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.
Other Name: ketamine
Study Arms  ICMJE Experimental: Nebulized Ketamine
sub-dissociative dose ketamine administered prehospitally via breath-actuated nebulizer at 1.0 mg/kg for patients with acute pain
Intervention: Drug: Nebutlized Ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: July 28, 2021)
0
Original Estimated Enrollment  ICMJE
 (submitted: November 12, 2019)
50
Actual Study Completion Date  ICMJE July 28, 2021
Actual Primary Completion Date July 28, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients 18 years of age and older
  • acute traumatic extremities injuries
  • a score of 5 or more on a standard 11- point (0 to 10) numeric rating scale.

Exclusion Criteria:

  • Patients with altered mental status,
  • allergy to ketamine, pregnant patients,
  • weight greater than 100 kg,
  • unstable vital signs (systolic blood pressure <90 or>180 mm Hg,
  • pulse rate <50 or >150 beats/min,
  • respiration rate <10 or >30 breaths/min),
  • inability to consent,
  • past medical history of alcohol or drug abuse
  • schizophrenia.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04162028
Other Study ID Numbers  ICMJE 2018-10-08
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Antonios Likourezos, Maimonides Medical Center
Study Sponsor  ICMJE Antonios Likourezos
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Maimonides Medical Center
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP