Study Results
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Basic Information
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COMPLETED
PHASE4
120 participants
INTERVENTIONAL
2017-11-06
2018-05-24
Brief Summary
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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.
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Detailed Description
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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.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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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.
Ketamine
Intranasal Ketamine administered via mucosal atomization device at 0.5 - 1 mg / kg IN.
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.
Normal Saline
Intranasal Normal Saline administered via mucosal atomization device.
Interventions
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Ketamine
Intranasal Ketamine administered via mucosal atomization device at 0.5 - 1 mg / kg IN.
Normal Saline
Intranasal Normal Saline administered via mucosal atomization device.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* A pain score of 5 or greater (signifying moderate or severe pain)
* Desire for analgesia when queried.
Exclusion Criteria
* 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
18 Years
ALL
No
Sponsors
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British Columbia Emergency Health Services
UNKNOWN
University of British Columbia
OTHER
Responsible Party
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Gary Andolfatto
Assistant Professor, University of British Columbia Department of Emergency Medicine
Principal Investigators
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Gary Andolfatto
Role: PRINCIPAL_INVESTIGATOR
University of British Columbia
Locations
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British Columbia Emergency Health Services Station 249
Surrey, British Columbia, Canada
Countries
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References
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Andolfatto G, Innes K, Dick W, Jenneson S, Willman E, Stenstrom R, Zed PJ, Benoit G. Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults. Ann Emerg Med. 2019 Aug;74(2):241-250. doi: 10.1016/j.annemergmed.2019.01.048. Epub 2019 Mar 27.
Related Links
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British Columbia Ambulance Service information page.
Other Identifiers
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H16-00554
Identifier Type: -
Identifier Source: org_study_id
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