Prehospital Analgesia in Adults Using Inhaled Methoxyflurane Study

Prehospital Analgesia in Adults Using Inhaled (PAIN) Methoxyflurane Study

This study is about a new pain relief medication called methoxyflurane. Pain from injuries, like broken bones, is a big reason people call ambulances. It's important to treat pain well because it can make people sick and slow down healing. But often, pain isn't treated enough, which can lead to more problems.

Paramedics use different drugs to manage pain, but some are hard to give and need special training and equipment. Methoxyflurane is a new option. It's a gas you breathe in through a special inhaler. It's been used in Australia and New Zealand for a long time and has shown to work quickly and safely for different kinds of pain.

This study wants to see if methoxyflurane works well for people with moderate to severe pain from injuries compared to other medicines like Advil, Tylenol and opioids. It's testing if methoxyflurane can give fast pain relief and if paramedics find it easy to use. The study will help understand if methoxyflurane could be a good option for treating pain in ambulances.

Study Overview

• Status: Not yet recruiting
• Conditions: Pain, Acute
• Intervention / Treatment: Other: Standard Care; Drug: Methoxyflurane

Detailed Description

The aim of this multi-centred study is to evaluate the prehospital use of methoxyflurane in patients ≥ 18 years of age presenting with moderate to severe pain (verbal numeric pain rating scale (NPRS) ≥ 4) secondary to trauma (which is defined as a physical injury of sudden onset and severity which requires immediate medical attention) as compared to other current therapies available to paramedics (NSAIDS and Opioids).

This will be a prehospital prospective stepped-wedge open-label, non-blinded, cluster randomized trial, enrolling patients with trauma related moderate to severe pain (numerical pain rating scale ≥4). It will be composed of three phases, involving a total of seven Ontario paramedic services. Our 24-month study will consist of the three following phases: 1) a 6-month setup and training period, followed by phase 2) the stepped-wedge trial (8-months) and phase 3) a 9-month period for data analysis and knowledge dissemination.

The verbal numeric pain rating scale (NPRS) is a subjective measure in which individuals rate their pain on an eleven-point numeric scale. The scale is comprised of values ranging from 0 (no pain at all) to 10 (worst imaginable pain). After ethics approvals have been secured for all sites, and after the initial 4-week observation period (where paramedics will provide standard care) one paramedic service will be randomized, using a number generator which the study team will be blinded, to the intervention condition (Methoxyflurane). Additional paramedic services will subsequently be randomized, and notified one by one at 4 week intervals until all seven paramedic services have been randomized to the intervention arm. Data will be collected for all eligible patients in each paramedic service for a total duration of 8 months. The study will be conducted in seven paramedic services in Eastern Ontario and will enrol patients who have been treated by paramedics, trained and authorized in the use and administration of methoxyflurane.

Eastern Ontario comprises 35 300 km2 and has a total regional population of 1.76 million. There are eight base hospitals in Ontario that provide medical direction, leadership and advice in the provision of prehospital emergency care. The Regional Paramedic Program for Eastern Ontario (RPPEO) is the base hospital which provides oversight to the seven included paramedic services. These paramedic services are comprised of 944 paramedics (738 of which are Primary Care Paramedics and 256 who are Advanced Care Paramedics). In summary, this study will comprise seven land paramedic services, operating in a catchment area of 10 rural counties and 4 cities, with 18 acute care hospitals and 1 university hospital.

• Study Type: Interventional
• Enrollment (Estimated): 1800
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Michael A Austin, MD; Phone Number: 6132970327; Email: maustin@toh.ca
• Study Contact Backup: Name: Jane Marchand; Phone Number: 6137377228; Email: jamarchand@rppeo.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Indications for analgesia therapy:

• Patients ≥ 18 years of age (using a waiver of consent process)
• Pain score ≥ 4 on the verbal numeric pain rating scale (NPRS)
• traumatic injury (defined as: physical injuries of sudden onset and severity which requires immediate medical attention)
• Unaltered (Glasgow Coma Scale (GCS) ≥ 14)
• Normotensive (systolic blood pressure ≥100)
• Treated and transported

Patients will be given methoxyflurane as soon as the treating paramedic has determined they meet inclusion criteria.

Paramedics will follow the Advanced Life Support Patient Care Standards21 for all other care the patient requires (including pain directive if methoxyflurane does not control pain after 10 min).

Contraindications listed in the ALS-PCS will be used by paramedics in providing analgesia. Within the standards paramedics are required to record vital signs every 5 minutes including verbal NPRS.

Exclusion Criteria:

Patients with the following characteristics will be excluded (based on the Health Canada Product Monograph):

• History or family history of malignant hyperthermia
• Age <18 years of age
• Pregnancy or breast-feeding
• Inclusion in another study not allowing the co-enrollment
• Known renal impairment
• Known liver disease
• History of use of methoxyflurane in the last 3 months
• Allergy to methoxyflurane

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control standard care; The patients who meet the indications of the study trauma-related pain Moderate/Severe (>4 verbal numeric pain score), are provided current standard of care for pain (Advil or Ketorolac/Tylenol, opioids (for Advanced Care paramedics)	Other: Standard Care; Patients ≥ 18 years of age (using a waiver of consent process) Pain score ≥ 4 on the verbal numeric pain rating scale (NPRS) traumatic injury (defined as: physical injuries of sudden onset and severity which requires immediate medical attention) Unaltered (Glasgow Coma Scale (GCS) ≥ 14) Normotensive (systolic blood pressure ≥100) Treated and transported
Experimental: Intervention; The patients who meet the indications of the study trauma-related pain Moderate/Severe (>4 verbal numeric pain score) and receive methoxyflurane	Drug: Methoxyflurane; Patients ≥ 18 years of age (using a waiver of consent process) Pain score ≥ 4 on the verbal numeric pain rating scale (NPRS) traumatic injury (defined as: physical injuries of sudden onset and severity which requires immediate medical attention) Unaltered (Glasgow Coma Scale (GCS) ≥ 14) Normotensive (systolic blood pressure ≥100) Treated and transported; Other Names: Penthrox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Verbal Numeric Pain Score	verbal numeric pain rating score (NPRS) initial and at 10 min, 0 referring to no pain and 10 severe pain	10 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rescue Medications	(as defined by addition of any other pain medication (ketorolac or opioids (fentanyl or morphine) 10 min after methoxyflurane administration, during paramedic care)	10 min
Transport Time	From time onscene, to hospital arrival	8 months
Time to first analgesia	time to first administration of analgesia (NSAIDs, Opioids or methoxyflurane)	8 months
Vital signs	vital signs (Blood pressure, Heart rate, oxygen saturation, temperature, respiratory rate, level of consciousness) (initial and at arrival to hospital) (repeat measures will be captured in data every 5 mins)	5 min
Verbal numeric pain score during care	verbal numeric pain rating score (NPRS) initial and at 10 min, 0 referring to no pain and 10 severe pain (as transport times will vary)	5 min

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	adverse events post administration of analgesia: any advanced airway interventions, oxygen requirement (oxygen saturations <94%), drop in blood pressure by 40% and/or <90 systolic, complaints of nausea or vomiting, malignant hyperthermia reaction).	8 months

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 19, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 18, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Ambulance; traumatic pain; paramedic
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Methoxyflurane
• Other Study ID Numbers: 20240319100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: de-identified data will be considered if requested for sharing.

Drug and device information, study documents

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