Clinical trial NCT02753114: Prehospital Analgesia With Intra-Nasal Ketamine
Official title: Prehospital Analgesia With Intra-Nasal Ketamine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain
Acute Pain
Keywords: Ketamine
Intranasal
Emergency Medical Services
Pain
Analgesia
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: British Columbia Emergency Health Services
First posted: 2016-04-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute painful conditions make-up a large proportion of pre-hospital transports in British Columbia (BC) yet Basic Life Support (BLS) paramedics have limited options to provide analgesia and therefore adequate and timely pain relief is often significantly delayed.

Inhaled nitrous oxide is commonly used as a pre-hospital analgesic and is considered "usual care" for pre-hospital providers in BC, but its utility in severe pain is uncertain. Moreover, nitrous oxide is limited in its effectiveness by a short duration of action, nausea, vomiting, and the necessity for patient cooperation.

IN Ketamine has been shown to provide rapid, easily-administered, and well-tolerated analgesia in many settings. The investigators believe that the addition of IN ketamine to usual care with nitrous oxide inhalation for adults experiencing moderate to severe intensity acute pain in the pre-hospital setting will result in improved pain severity, improved patient-reported comfort, and improved patient satisfaction.

Detailed description: Purpose:

The purpose of this study is to see whether intra-nasal (IN) Ketamine (50 mg / ml) solution (Sandoz; Drug Identification Number (DIN) 02246796) administered via mucosal atomization device (LMA MAD300 Nasal TM; Wolfe Tory Medical Inc., San Diego, CA), in addition to usual care with nitrous oxide inhalation, to pre-hospital patients being transported by British Columbia Emergency Health Services (BC EHS) Basic Life Support (BLS) paramedics with moderate to severe pain (pain \> 5/10 on a validated numerical rating scale or NRS) will improve pain relative to usual care plus placebo.

Hypothesis:

It is hypothesized that the addition of IN ketamine to usual care with nitrous oxide inhalation for adults experiencing moderate to severe intensity acute pain in the pre-hospital setting will result in a greater proportion of patients experiencing a 2-point or more reduction in verbal numerical rating scale (VNRS) pain score within 30 minutes, as well as improved patient-reported comfort, reduced nitrous oxide requirements, and improved patient and provider satisfaction compared to usual care alone.

Background:

Acute painful conditions make-up a large proportion of pre-hospital transports yet BLS paramedics have limited options to provide analgesia, and therefore, adequate and timely pain relief is often significantly delayed. Inhaled nitrous oxide is commonly used as a pre-hospital analgesic and is considered "usual care" for BLS pre-hospital providers. Nitrous oxide has been shown to be effective for analgesia in patients with moderate pain but its utility in severe pain is uncertain. No alternative treatments exist for BLS providers in the pre-hospital setting. Intra-nasal ketamine is a safe, well-tolerated means of providing analgesia and has been proven to work in the pre-hospital setting without the need for cardio-respiratory monitoring.

Objectives:

The objective of this study is to collect pilot data to compare the addition of intranasal Ketamine or an intranasal placebo in terms of efficacy and effectiveness in patients receiving usual care with nitrous oxide for moderate to severe pain.

Secondary objectives will be to assess subjective improvement in pain, effect on nitrous oxide requirements, incidence of adverse effects, patient and provider satisfaction, and study recruitment potential. These data will inform future large-scale trial designs and will be used to validate a proposed 7-point patient-reported pain improvement scale.

Research Methods:

This will be a randomized double-blind pilot trial conducted in the pre-hospital setting in the lower mainland. The pilot series will constitute 40 patients (20 per group). The sample size for a larger randomized controlled trial will then be calculated using the effect size and variance of the accrued data.

Statistical Analysis:

A statistician will be contracted to independently oversee the analysis of study results. The intention-to-treat principal will be used to analyze all data. Data will be analyzed using descriptive statistics. Categorical data will be presented as frequency and percentage frequency of occurrence. Continuous data will be presented as medians with ranges and interquartile ranges (IQRs). Adverse effects will be described as frequency of occurrence with 95% confidence intervals. A p-value of 0.05 will be considered statistically significant.

Eligibility criteria: Inclusion Criteria:

* Patients who have an acute painful condition, as determined by the Emergency Health Services attendant
* A pain score of 5 or greater (signifying moderate or severe pain)
* Desire for analgesia when queried.

Exclusion Criteria:

* Less than 18 years of age.
* Previous hypersensitivity, intolerance or allergy to ketamine
* Chest pain
* Altered mental status
* Inability self-report pain score
* Pregnancy
* Nasal occlusion
* Systolic Blood Pressure \< 90 mm Hg
* Requiring immediate attention of the paramedic
* Ineligible to receive inhaled nitrous oxide as per BC EHS protocols

Primary outcomes:
measure: Proportion experiencing 2-point or more pain score reduction at 30 minutes
timeFrame: 30 minutes.
Secondary outcomes:
measure: Proportion experiencing 2-point or more pain score reduction at 15 minutes
timeFrame: 15 minutes
measure: The proportion of patients feeling "a lot better" or "moderately better" at 30 minutes post medication delivery or hospital at hospital arrival
timeFrame: 30 minutes
measure: The proportion of patients feeling "a lot better" or "moderately better" at 15 minutes.
timeFrame: 15 minutes
measure: The proportion of patients feeling "a lot better", "moderately better" or "a little better" at 15 minutes and at 30 minutes.
timeFrame: 15 minutes, 30 minutes
measure: Adverse Events
timeFrame: Every 15 minutes until care transferred to Emergency Department
measure: Patient Satisfaction
timeFrame: At 30 minutes post analgesia administration.
measure: Provider Satisfaction
timeFrame: At 30 minutes post analgesia administration.
measure: Median Nitrous Oxide Consumption
timeFrame: At 30 minutes post analgesia administration.
measure: Median reduction in pain score at 15 minutes
timeFrame: 15 minutes
measure: Median reduction in pain score at 30 minutes
timeFrame: 30 minutes
Other outcomes:
Locations:
city: Surrey
country: Canada
facility: British Columbia Emergency Health Services Station 249
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Gary Andolfatto
role: PRINCIPAL_INVESTIGATOR
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