PENTHROX™ in the Canadian Emergency Department (ED) (ADVANCE-ED)

A Phase IV Real World Study on the Use of Low Dose Methoxyflurane (PENTHROX™) for the Treatment of Moderate to Severe Trauma Pain in the Canadian Emergency Department

This Canadian, multi-centre, prospective, real world study is designed to evaluate the effectiveness of low dose methoxyflurane (MEOF) (PENTHROX™) for the treatment of moderate to severe pain associated with trauma in the Canadian ED.

Study Overview

• Status: Completed
• Conditions: Pain, Acute
• Intervention / Treatment: Drug: Methoxyflurane 3mL

Detailed Description

The study will assess the change in pain intensity over 20 minutes from start of administration of PENTHROX™ and will generate Real World Evidence in support of existing clinical trial data including effectiveness, safety and additional parameters of low dose MEOF (PENTHROX™) in Canadian EDs.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H3A7
      • Charles V Keating Emergency and Trauma Centre, QEII
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Markham, Ontario, Canada, L3P 7P3
      • Markham Stouffville
    • Welland, Ontario, Canada, L3B4W6
      • St. Joseph's Healthcare
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Centre Integre Universitaire De Sante Et De Service Sociaux (CIUSSS) Saguenay-Lac-Saint Jean
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Centre Intégré de Santé et de Services Sociaux de la Montérégie-Centre

Participation Criteria

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:

1. Conscious adult patients: ≥ 18 years of age

2. Moderate to severe pain associated with trauma (NRS0-10 ≥ 4) which is unlikely to require surgery/hospitalization, such as

   • Musculoskeletal injuries and physical wounds
   • Fractures
   • Lacerations
   • Burns
   • Dislocations
   • Contusions
   • Injury due to foreign bodies
3. Patient (and/or patient's authorized legal representative) should understand the nature of the study and provide written informed consent
4. Patient is able to follow all study requirements and procedures and complete required questionnaires

Exclusion Criteria:

1. Multi-level trauma
2. Women of child bearing potential who are pregnant or peri partum, including labour
3. An altered level of consciousness, due to any cause, including head injury, drugs, or alcohol
4. Clinically significant renal impairment
5. A history of liver dysfunction after previous MEOF use or other halogenated anesthetics
6. Hypersensitivity to MEOF or other halogenated anesthetics, or to butylated hydroxytoluene
7. Known or genetically susceptible to malignant hyperthermia or a history of severe adverse reactions in either patient or relatives
8. Exacerbation of an underlying condition (i.e., chronic pain)
9. Clinically evident or potential hemodynamic instability as per the opinion of the investigator
10. Clinically evident respiratory impairment as per the opinion of the investigator
11. Prior treatment with PENTHROX within 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Methoxyflurane (MEOF)-active treatment; single arm study all subjects will be treated with Methoxyflurane 3 mL

Drug: Methoxyflurane 3mL; As soon as possible following enrollment and initial procedures, the patient will be supplied with a PENTHROX™ kit which includes one inhaler containing 3 mL of MEOF for pain management. A member of the research team will train the patient to self-administer MEOF. PENTHROX™ is an approved (trademarked) product in Canada and is commercially available in a combination blister pack with one 3 mL sealed bottle and one PENTHROX™ inhaler with the Activated Carbon (AC) chamber.; Other Names: PENTHROX™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in mean pain intensity: Numerical Rating Scale	The level of pain intensity will be collected by means of the Numerical Rating Scale (NRS). The NRS is considered a reliable and valid scale for assessing pain intensity and is preferred by patients for its simplicity. In this 11-point scale, the end points are the extremes of no pain and pain as bad as it could be, or worst pain (i.e. a score of 0 = no pain and a score of 10 = worst pain possible). Assessed by the patient 20 mins post PENTHROX™ inhalation	20 mins from start of administration (STA) of PENTHROX™

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Speed of action of analgesia	Speed of action of analgesia is defined as the time at which the patient experiences meaningful pain relief following inhalation of PENTHROX™. The healthcare professional will instruct the patient to note the time at which they experience meaningful pain relief. The time point will be recorded in the case report form.	At any point from STA of PENTHROX™ to 20 mins post inhalation
Proportion of treatment-emergent adverse events (TEAEs)	Assessment of patient reported adverse events throughout the observation period.	At any point From STA of PENTHROX™ until the end of the observation period (24 hours)
Global Medication Performance (GMP) before discharge from ED (Patient & Health Care Professional)	Global medication performance (GMP) is an assessment of the health care professional's and patient's impression of how well a medication works. Global Medication Performance (GMP)-is a patient and health care provider reported outcome with the objective of assessing the health care professional's and patient's impression of how well a medication works. GMP is measured by asking the patient and health care professional a single question: "rate the pain relief provided by PENTHROX™" utilizing a 5-point Likert scale where 1=Poor- 5=Excellent	at 20 minutes From STA of PENTHROX™ and at the end of the observation period (up to 24hours)
Fulfillment of pain relief expectations (Patient & Healthcare professional)	Fulfillment of pain relief expectations- is a patient and health care professional reported outcome with the objective of assessing the health care professional's and patient's impression of how well a medication fulfilled their expectations. Fulfillment of pain relief expectations is measured by asking the patient and health care professional a single question: "To what extent has your expectations regarding pain control been met" and utilizing a 5-point Likert scale where 1=Poor- 5=Excellent.	At the end of the observation period (up to 24hours)
Use of rescue medication	The time of first use of rescue medication after STA of PENTHROX™ up to and including 60 minutes will be documented.	From STA of PENTHROX™ to the end of the observation period (up to 24hours)

Collaborators and Investigators

• Sponsor: Purdue Pharma, Canada
• Investigators: Study Director: Sonja Dhani, PhD, Purdue Pharma, Canada

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2019
• Primary Completion (Actual): March 30, 2020
• Study Completion (Actual): September 8, 2020

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: March 6, 2019
• First Posted (Actual): March 11, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 14, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Disease Attributes; Emergencies; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Methoxyflurane
• Other Study ID Numbers: CAN-MEOF-MA-OO1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No