Prehospital Analgesia With Intra-Nasal Ketamine (PAIN-K)

October 18, 2018 updated by: Gary Andolfatto, University of British Columbia

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

120

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Surrey, British Columbia, Canada, V3V 1Z2
        • British Columbia Emergency Health Services Station 249

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intranasal Ketamine
Ketamine dosing will be weight-based as follows: 30mg of IN ketamine for patients weighing 50 kg or less; 50 mg of IN ketamine for patients weighing 50 kg to 100 kg; and 75 mg of IN ketamine for patients weighing greater than 100 kg (i.e. 0.5 mg/kg to 1.0 mg/kg of intranasal ketamine). Syringes containing ketamine will be prepared from the intravenous formulation of Ketamine (50 mg / ml) solution (Sandoz; DIN 02246796) and stored in pre-filled 5 ml syringes. Ketamine will be administered to patients through a mucosal atomization device. One-half of the pre-specified volume will be administered into each nare. No repeat doses will be administered.
Drug: Ketamine
Intranasal Ketamine administered via mucosal atomization device at 0.5 - 1 mg / kg IN.
Other Names:
  • Ketalar
  • Sandoz DIN 02246796
Placebo Comparator: Placebo
Syringes containing normal saline will be prepared such that the volume of normal saline in 5 ml syringes matches that of the ketamine for each of the weight based groups previously specified in the Treatment Arm Description. Syringes containing normal saline will also be labeled "Study Drug". The normal saline will also be administered to patients through a mucosal atomization device. One-half of the pre-specified volume will be administered into each nare. No repeat doses of placebo will be administered.
Drug: Normal Saline
Intranasal Normal Saline administered via mucosal atomization device.
Other Names:
  • Saline placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion experiencing 2-point or more pain score reduction at 30 minutes
Time Frame: 30 minutes.
The proportion of patients experiencing a 2-point or more reduction in NRS pain score at 30 minutes.
30 minutes.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion experiencing 2-point or more pain score reduction at 15 minutes
Time Frame: 15 minutes
The proportion of patients experiencing a 2-point or more reduction in NRS pain score at 15 minutes.
15 minutes
The proportion of patients feeling "a lot better" or "moderately better" at 30 minutes post medication delivery or hospital at hospital arrival
Time Frame: 30 minutes
The proportion of patients feeling "a lot better" or "moderately better" at 30 minutes post medication delivery or hospital at hospital arrival
30 minutes
The proportion of patients feeling "a lot better" or "moderately better" at 15 minutes.
Time Frame: 15 minutes
The proportion of patients feeling "a lot better" or "moderately better" at 15 minutes.
15 minutes
The proportion of patients feeling "a lot better", "moderately better" or "a little better" at 15 minutes and at 30 minutes.
Time Frame: 15 minutes, 30 minutes
The proportion of patients feeling "a lot better", "moderately better" or "a little better" at 15 minutes and at 30 minutes.
15 minutes, 30 minutes
Adverse Events
Time Frame: Every 15 minutes until care transferred to Emergency Department
Incidence of adverse events.
Every 15 minutes until care transferred to Emergency Department
Patient Satisfaction
Time Frame: At 30 minutes post analgesia administration.
Patient satisfaction with analgesia provided using a ten point numeric rating scale anchored with 0 = "not at all satisfied" and 10 = "completely satisfied" on hospital arrival.
At 30 minutes post analgesia administration.
Provider Satisfaction
Time Frame: At 30 minutes post analgesia administration.
Paramedic satisfaction with analgesia provided using a ten point numeric rating scale anchored with 0 = "not at all satisfied" and 10 = "completely satisfied" on hospital arrival.
At 30 minutes post analgesia administration.
Median Nitrous Oxide Consumption
Time Frame: At 30 minutes post analgesia administration.
Median nitrous oxide consumption in each group will be recorded and compared.
At 30 minutes post analgesia administration.
Median reduction in pain score at 15 minutes
Time Frame: 15 minutes
Median reduction in NRS pain score at 15 minutes
15 minutes
Median reduction in pain score at 30 minutes
Time Frame: 30 minutes
Median reduction in NRS pain score at 30 minutes
30 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Collaborators

British Columbia Emergency Health Services

Investigators

  • Principal Investigator: Gary Andolfatto, University of British Columbia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 6, 2017

Primary Completion (Actual)

May 24, 2018

Study Completion (Actual)

May 24, 2018

Study Registration Dates

First Submitted

April 16, 2016

First Submitted That Met QC Criteria

April 22, 2016

First Posted (Estimate)

April 27, 2016

Study Record Updates

Last Update Posted (Actual)

October 22, 2018

Last Update Submitted That Met QC Criteria

October 18, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H16-00554

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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